Lipid-based nanocarriers have staged a remarkable comeback in the oral delivery of proteins and peptides, but delivery efficiency is compromised by lipolysis. β-Lactoglobulin(β-lg) stabilized lipid nanoparticles, in...Lipid-based nanocarriers have staged a remarkable comeback in the oral delivery of proteins and peptides, but delivery efficiency is compromised by lipolysis. β-Lactoglobulin(β-lg) stabilized lipid nanoparticles, including nanoemulsions(NE@β-lg) and nanocapsules(NC@β-lg), were developed to enhance the oral absorption of insulin by slowing down lipolysis due to the protection from β-lg. Cremophor EL stabilized nanoemulsions(NE@Cre-EL) were prepared and set as a control. The lipid nanoparticles produced mild and sustained hypoglycemic effects, amounting to oral bioavailability of 3.0% ± 0.3%, 7.0% ± 1.1%, and7.7% ± 0.8% for NE@Cre-EL, NE@β-lg, and NC@β-lg, respectively. Aggregation-caused quenching(ACQ)probes enabled the identification of intact nanoparticles, which were used to investigate the in vivo and intracellular fates of the lipid nanoparticles. In vitro digestion/lipolysis and ex vivo imaging confirmed delayed lipolysis from β-lg stabilized lipid nanoparticles. NC@β-lg was more resistant to intestinal lipolysis than NE@β-lg due to the Ca^(2+)-induced crosslinking. Live imaging revealed the transepithelial transport of intact nanoparticles and their accumulation in the liver. Cellular studies confirmed the uptake of intact nanoparticles. Slowing down lipolysis via food proteins represents a good strategy to enhance the oral absorption of lipid nanoparticles and thus co-formulated biomacromolecules.展开更多
Probiotics crosstalk immunity to improve host glycolipid metabolism,which is a new strategy for obesity.This study aimed to explore the functions of Lacticaseibacillus paracasei K56(K56),in regulating the lipid metabo...Probiotics crosstalk immunity to improve host glycolipid metabolism,which is a new strategy for obesity.This study aimed to explore the functions of Lacticaseibacillus paracasei K56(K56),in regulating the lipid metabolism of adipocytes and its immune regulation mechanisms.We co-cultured RAW264.7 macrophages with K56,and the K56-stimulated RAW264.7-conditioned medium(K56-CM)was collected and treated with 3T3-L1 pre-adipocytes.The expression of lipid metabolism-related markers of adipocytes,and the content of cytokines in CMs were detected.The results demonstrated that K56-CM promoted the expression of peroxisome proliferator-activated receptor-γ(PPAR-γ),CCAAT/enhancer binding proteinα(C/EBPα),and other adipogenesis-related markers,which resulted in the upregulation of lipolysis markers,such as hormone-sensitive lipase(HSL),adipose triglyceride lipase(ATGL).The activation of lipolysis enhanced the expression of fatty acidβ-oxidation-related and mitochondrial biogenesis-related markers and reduced lipid accumulation in adipocytes.The glycolipid metabolism pattern of K56 may be due to its immunomodulatory characteristics,which stimulated macrophages to secrete fewer TNF-α,thereby promoting the expression of lipolysis-related markers,and TNF-αsynergized with lipase to promote lipolysis.It has not been reported that L.paracasei modulated lipid metabolism via the lipolysis pathway,which suggested that K56 may regulate glycolipid metabolism of the host by maintaining immune homeostasis.展开更多
Background As cows transition from pregnancy to lactation,free fatty acids(FFA)are mobilized from adipose tissues(AT)through lipolysis to counter energy deficits.In clinically healthy cows,lipolysis intensity is reduc...Background As cows transition from pregnancy to lactation,free fatty acids(FFA)are mobilized from adipose tissues(AT)through lipolysis to counter energy deficits.In clinically healthy cows,lipolysis intensity is reduced throughout lactation;however,if F FA release exceeds tissue demands or the liver's metabolic capacity,lipid byproducts accumulate,incre a sing cows'risk of metabolic and infectious disease.Endocannabinoids(eCBs)and their congeners,N-acylethanolamines(NAEs),are lipid-based compounds that modulate metabolism and inflammation.Their synthesis and release depend upon the availability of FFA precursors and the abundance of synthesizing and degrading enzymes and transporters.Therefore,we hypothesized that eCB production and transcription of endocannabinoid system components are modulated by lipolysis pathways in adipocytes.To test this hypothesise we stimulated canonical(isoproterenol,1μmol/L;ISO)and inflammatory(lipopolysaccharide,1μg/m L;LPS)lipolysis pathways in adipocytes isolated from the AT of 5 Holstein dairy cows.Following,we assessed lipolysis intensity,adipocytes'release of eCBs,and transcription of endocannabinoid system components.Results We found that ISO and LPS stimulated lipolysis at comparable intensities.Exposure to either treatment tended to elevate the release of eCBs and NAEs by cultured adipocytes;however,specific eCBs and NAEs and the transcriptional profiles differed by treatment.On one hand,ISO enhanced adipocytes'release of 2-arachidonoylglycerol(2-AG)but reduced NAE production.Klotably,ISO enhanced the cells"expression of enzymes associated with 2-AG biosynthesis(INPP5F,GDPD5,GPAT4),transport(CD36),and adipogenesis(PPARG).Conversely,LPS enhanced adipocytes'synthesis and release of N-arachidonoylethanolamide(AEA).This change coincided with enhanced transcription of the NAE-biosynthesizing enzyme,PTPN22,and adipocytes'transcription of genes related to eCB degradation(PTGS2,MGLL,CYP27B1).Furthermore,LPS enhanced adipocytes'transcription of eCB and NAE transporters(HSPA1A,SCP2)and the expression of the anti-adipogenic ion channel,TRPV3.Conclusions Our data provide evidence for distinct modulatory roles of canonical and inflammatory lipolysis pathways over eCB release and transcriptional regulation of biosynthesis,degradation,transport,and ECS signaling in cows'adipocytes.Based on our findings,we conclude that,within adipocytes,eCB production and ECS component expression are,at least in part,mediated by lipolysis in a pathway-dependent manner.These findings contribute to a deeper understanding of the molecular mechanisms underlying metabolic regulation in dairy cows'AT,with potential implications for prevention and treatment of inflammatory and metabolic disorders.展开更多
Objective: To investigate the influence of central administration ofneuropeptide Y-Y5 receptor antisense oligodeoxynucleotides (ODNs) on body weight, fat pads of SDrats, and the effects of white adipocytes lipolysis a...Objective: To investigate the influence of central administration ofneuropeptide Y-Y5 receptor antisense oligodeoxynucleotides (ODNs) on body weight, fat pads of SDrats, and the effects of white adipocytes lipolysis and apoptosis. Methods: Y5 receptor antisense,sense, mismatched ODNs or vehicle was intracerebroventricularly (i. c. v.) injected. Averageadipocyte area was calculated. DNA ladders were measured to evaluate adipocyte apoptosis, and RT-PCRwas used to analyse the expression of Bcl-2 and Bax gene. Results: Central administration of Y5antisense ODNs significantly decreased body weight, and average adipocyte area. DNA fragmentationwas present after electrophoresis at epididymal adipose tissue. The expression of Bcl-2 gene wasdownregulated, while the expression of Bax upregulated. Conclusion: Lipolysis and adipocyteapoptosis may be important mechanisms far 75 antisense therapy.展开更多
Insulin resistance is characterized as one of crucial pathological changes in type 2 diabetes mellitus（T2DM）, and dyslipidaemia is frequently detected in T2DM. A variety of vanadium compounds have been studied as dr...Insulin resistance is characterized as one of crucial pathological changes in type 2 diabetes mellitus（T2DM）, and dyslipidaemia is frequently detected in T2DM. A variety of vanadium compounds have been studied as drug candidates for diabetes based on their insulin-like action. However, few studies focus on their antilipolytic effect. In the present study, we established an insulin-resistant model in 3T3-L1 adipocytes to mimic pathological conditions of T2DM according to a well-established method by the treatment of high concentrations of glucose and insulin, which was validated by oil red O staining and the decreased levels of phosphorylated Akt, AS160 and GSK3 after insulin treatment. The results demonstrated that bis（acetylacetonato）-oxidovanadium（Ⅳ）（VO（acac）_2） could inhibit isoproterenol-stimulated lipolysis through the reduction of the phosphorylated HSL and perilipin levels in both insulin-sensitive and insulin-resistant 3T3-L1 adipocytes. Moreover, although the levels of phosphorylated Akt induced by VO（acac）_2 were decreased, the rates of lipolytic inhibition were not significantly altered compared with those under insulin-sensitive condition, indicating that the anti-lipolytic effect of VO（acac）_2 might also function in an Akt-independent way in insulin-resistant adipocytes. Our work here help elucidate the anti-diabetic effects of vanadium compounds. It may not only shed light on the utility of vanadium-based compounds as potential anti-diabetic drugs but also serve as a useful screening model for new anti-diabetic drugs.展开更多
Elevated concentrations of plasma fatty acids in transition dairy cows are significantly associated with increased disease susceptibility and poor lactation performance. The main source of plasma fatty acids throughou...Elevated concentrations of plasma fatty acids in transition dairy cows are significantly associated with increased disease susceptibility and poor lactation performance. The main source of plasma fatty acids throughout the transition period is lipolysis from adipose tissue depots. During this time, plasma fatty acids serve as a source of calories mitigating the negative energy balance prompted by copious milk synthesis and limited dry matter intake.Past research has demonstrated that lipolysis in the adipose organ is a complex process that includes not only the activation of lipolytic pathways in response to neural, hormonal, or paracrine stimuli, but also important changes in the structure and cellular distribution of the tissue in a process known as adipose tissue remodeling. This process involves an inflammatory response with immune cell migration, proliferation of the cellular components of the stromal vascular fraction, and changes in the extracellular matrix. This review summarizes current knowledge on lipolysis in dairy cattle, expands on the new field of adipose tissue remodeling, and discusses how these biological processes affect transition cow health and productivity.展开更多
In the present study, we investigated the role of reactive oxygen species（ROS） elevation induced by an anti-diabetic vanadium compound, vanadyl acetylacetonate（VO（acac）2）, in the regulation of lipolysis and gluc...In the present study, we investigated the role of reactive oxygen species（ROS） elevation induced by an anti-diabetic vanadium compound, vanadyl acetylacetonate（VO（acac）2）, in the regulation of lipolysis and glucose metabolism using differentiated 3T3L1 adipocytes as a model system. By confocal laser scanning microscopy, we found that VO（acac）2 induced ROS generation under high glucose stimulation, and the pretreatment of NADPH oxidase inhibitors could significantly reduce the elevated ROS level. Meanwhile, the decreased phosphorylated levels of AKT and the two key modulators of lipolysis（HSL and perilipin） were observed by western blot analysis. We also found that the contents of glycerol release were further reduced as well. In addition, the levels of key regulatory proteins, AS160 and GSK3β, in glucose metabolism pathway were correspondingly reduced. These findings demonstrated that ROS induced by vanadium compounds could act as a metabolic signal to activate AKT pathway to inhibit lipolysis and promote glucose transport and glycogen synthesis rather than by direct action by themselves. Our study contributed to elucidate the anti-diabetic effects of vanadium compounds and provided a theoretical basis for the further development of new vanadium complexes in the prevention and therapeutics of diabetes.展开更多
Hatchery-roared juvenile black sea breams are characterized by a low level of highly unsaturated fatty acids in their bodies, as compared with wild fish. To assess the effect of docosahaxaenoic acid （DHA） on lipegen...Hatchery-roared juvenile black sea breams are characterized by a low level of highly unsaturated fatty acids in their bodies, as compared with wild fish. To assess the effect of docosahaxaenoic acid （DHA） on lipegenic and lipelysis enzymes, one-year fish were roared on a casein-based purified diet and a DHA fortified diet （ 1.5% DHA ethyl ester/kg diet） for 60 d, followed with a period of 55 d for starvation. Dietary DHA was effectively incorporated into the fish body. Fortification of DHA depressed activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase as lipogenic enzymes in the hepatopancroas and intraperitoneal fat body. Carnitine palmitoyltransferase as lipolysis enzyme in the hepatopancreas was active in the DHA fortified fish. Starvation after feeding experiment induced increased carnitine palmitoyltransferase activity in both control and DHA fortified fish and the activity remained higher in the DHA fortified fish, while the monoenes were selectively consumed prior to highly unsaturated fatty acids. These results indicated that dietary DHA depressed lipogenesis and activated lipolysis.展开更多
The effect of sodium chloride(NaCl)curing salt content on protein oxidation,lipid oxidation and lipolysis of Chinese dry sausage was investigated.Two groups Chinese dry sausages with 2%and 4%(m/m)salt content were stu...The effect of sodium chloride(NaCl)curing salt content on protein oxidation,lipid oxidation and lipolysis of Chinese dry sausage was investigated.Two groups Chinese dry sausages with 2%and 4%(m/m)salt content were studied.The degree of protein oxidation increased during the processes in two groups sausages,while the content of phospholipids decreased,neutral lipids and free fatty acids increased.The degree of protein oxidation,lipid oxidation and lipolysis in 4%NaCl content group was higher than those in 2%NaCl content group,while 4%NaCl content group has higher lipase activity.In conclusion,4%NaCl may facilitate the protein oxidation,lipid hydrolysis and oxidation in Chinese dry sausage,and the protein oxidation had strong correlation with lipid oxidation and lipolysis.The results could provide a basis for improving the technology of industrial production.展开更多
Simiao Wan(SMW)is a traditional Chinese formula,including Atractylodis Rhizoma,Achyranthis Bidentatae Radix,Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2.It can be used to the treatment of dia...Simiao Wan(SMW)is a traditional Chinese formula,including Atractylodis Rhizoma,Achyranthis Bidentatae Radix,Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2.It can be used to the treatment of diabetes.However,its bioactive compounds and underlying mechanism are unclear.This study was designed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance.Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activity was screened in fasted mice.The effects of 60%ethanol elution(ESMW)on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid(PA)and high fat diet(HFD)-fed mice.In our study,ESMW was the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS.ESMW suppressed protein kinase A(PKA)-hormone-sensitive lipase(HSL)related lipolysis and increased AMP-activated protein kinase(AMPK)phosphorylation in PA challenged 3T3-L1 adipocytes.AMPKa knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660,revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent.Furthermore,ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice.It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis.Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells,demonstrating that the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production.In conclusion,ESMW,as the antilipolytic fraction of SMW,inhibited PKA-HSL related lipolysis by activating AMPK,inhibiting diacylglycerol(DAG)accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.展开更多
OBJECTIVE： Traditional Korean Chungtaejeon （CTJ） tea is a type of fermented tea, which has received increasing attention in recent years because of its purported health benefits. The present study was designed to i...OBJECTIVE： Traditional Korean Chungtaejeon （CTJ） tea is a type of fermented tea, which has received increasing attention in recent years because of its purported health benefits. The present study was designed to investigate the effect and mechanism of CTJ tea extract on body weight gain using C57BL/6J-Lep ob/ob mice and 3T3-L1 adipocytes, respectively. METHODS： The effects of CTJ on cell viability, lipid accumulation, and expression of protein and mRNA were measured in 3T3-L1 adipocytes by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, oil red O staining, Western blotting, and reverse transcriptase-polymerase chain reaction analyses. C57BL6J-Lep ob/ob mice were administered with CTJ （200 or 400 mg/kg body weight） for ten weeks. Then, body weight, food intake, total cholesterol, and triglyceride were measured in ob/ob mice. RESULTS： CTJ tea extract treated at 250 wg/mL （CTJ250） significantly suppressed lipid accumulation in the differentiated 3T3-L1 adipocytes. Likewise, CTJ250 significantly decreased the protein expression of peroxisome proliferator-activated receptor Y （PPARy）, CCJ^u~,T/enhancer-binding protein a, and adipocyte lipid- binding protein, and regulated the mRNA expression of PPART, sterol regulatory element-binding protein- lc gene, fatty acid synthase, adipocyte lipid-binding protein, hormone-sensitive lipase, carnitine palmitoyl transferase 1, cluster of differentiation 36, and acetyl-CoA carboxylase in the differentiated 3T3-L1 adipocytes. Mice administered with CTJ showed dose-dependent decrease in body weight gain, starting from week 4 of the experiment. CTJ tea extract administered at 400 mg/kg body weight significantly decreased fat mass, food efficacy ratio, and levels of plasma triglyceride and total cholesterol. CONCLUSION： CTJ attenuated weight gain in ob/ob mice and regulated the activity of the molecules involved in adipogenesis and lipolysis in 3T3-L1 adipocytes. CTJ is a potentially valuable herbal therapy for the prevention of obesity and/or obesity-related disorders.展开更多
With many advantages such as non-invasive,safe and quick effect,focused ultrasound lipolysis stands out among many fat-removing methods.However,during the whole process,the doctor needs to hold the ultrasound transduc...With many advantages such as non-invasive,safe and quick effect,focused ultrasound lipolysis stands out among many fat-removing methods.However,during the whole process,the doctor needs to hold the ultrasound transducer and press it on the patient’s skin with a large pressure for a long time;thus the probability of muscle and bone damage for doctors is greatly increased.To reduce the occurrence of doctors’occupational diseases,a depth camera-based ultrasonic lipolysis robot system is proposed to realize robot-assisted automatic ultrasonic lipolysis operation.The system is composed of RealSense depth camera,KUKA LBR Med seven-axis robotic arm,PC host,and ultrasonic lipolysis instrument.The whole operation includes two parts:preoperative planning and intraoperative operation.In preoperative planning,the treatment area is selected in the camera image by the doctor;then the system automatically plans uniformly distributed treatment points in the treatment area.At the same time,the skin normal vector is calculated to determine the end posture of the robot,so that the ultrasound transducer can be pressed down in the normal direction of skin.During the intraoperative operation,the robot is controlled to arrive at the treatment point in turn.Meanwhile,the patient’s movement can be detected by the depth camera,and the path of robot is adjusted in real time so that the robot can track the movement of patient,thereby ensuring the accuracy of the ultrasonic lipolysis operation.Finally,the human body model experiment is conducted.The results show that the maximum error of the robot operation is within 5mm,average error is 3.1mm,and the treatment points of the robot operation are more uniform than those of manual operation.Therefore,the system can replace the doctor and achieve autonomous ultrasonic lipolysis to reduce the doctor’s labor intensity.展开更多
Vaccarin,a flavonoid glycoside isolated from Vaccaria segetalis,is non-toxic to 3T3-L1 cells up to concentrations of 200μM.Accordingly,we investigated the effects of this natural product on adipogenesis and lipolysis...Vaccarin,a flavonoid glycoside isolated from Vaccaria segetalis,is non-toxic to 3T3-L1 cells up to concentrations of 200μM.Accordingly,we investigated the effects of this natural product on adipogenesis and lipolysis in 3T3-L1 adipocytes.Our results revealed that vaccarin significantly inhibited lipid accumulation by suppressing the adipogenesis-related transcription factors peroxisome proliferator-activated receptorγ(PPARγ)and the CCAAT/enhancer-binding proteinα(C/EBPα).Specifically,lipid accumulation decreased by up to 27.7±2.7%when 3T3-L1 adipocytes were treated with a 10μM concentration of vaccarin.Mechanistic studies showed that the compound inhibited adipogenesis through activation of the Hedgehog(Hh)signaling pathway and so restoring Smo and Gli1 expression at an early stage of differentiation.In mature 3T3-L1 cells,vaccarin significantly increased the secretion of glycerol into the surrounding medium and thus indicating that it accelerated the degradation of triglycerides.In addition,vaccarin,was shown to enhance lipolysis through stimulation of the transcription levels of lipoprotein lipase,monoglycerides lipase,adipose triacylglyceride lipase,hormone-sensitive lipase and adipose differentiated-related protein.All told,vaccarin suppressed lipid accumulation and enhanced lipolysis during adipocyte differentiation by restoring Hh signaling.As such,it is a phytochemical capable of halting adipocyte hyperplasia and,thereby,ameliorating the effects of obesity.展开更多
Obesity has brought great challenges to global human health,and how to effectively prevent and control the occurrence and development of obesity has become an urgent problem.The role and mechanism of 4-[(α-Lrhamnosyl...Obesity has brought great challenges to global human health,and how to effectively prevent and control the occurrence and development of obesity has become an urgent problem.The role and mechanism of 4-[(α-Lrhamnosyloxy)benzyl]isothiocyanate(MITC),an active ingredient of Moringa oleifera Lam.,in the regulation of lipid metabolism have not been comprehensively investigated.In the present study,we investigated the mechanism of MITC in inhibiting lipid accumulation in mice fed with a high-fat diet(HFD)in terms of both lipolysis and central appetite regulation mediated by the gut microbe-gut-brain axis.MITC enhanced the characteristic indices associated with HFD mice and also promoted adipocytolysis and brown fat thermogenesis.Moreover,MITC was observed to improve leptin resistance,modulate the composition of gut microbiota such as Ruminococcaceae,Parasutterella,and Acetatifactor,promote 5-hydroxytryptamine secretion,further enhance the secretion of glucagon-like peptide-1(GLP-1)and peptide tyrosine-tyrosine(PYY)to activate peroxisome proliferator-activated receptor(PPAR)signaling in the hypothalamus,and modulate feeding behavior to inhibit lipid accumulation in HFD mice.These data suggest that MITC supplementation can help to alleviate obesity or obesity-related diseases.展开更多
Self-microemulsifying drug delivery systems(SMEDDSs)have recently returned to the limelight of academia and industry due to their enormous potential in oral delivery of biomacromolecules.However,information on gastroi...Self-microemulsifying drug delivery systems(SMEDDSs)have recently returned to the limelight of academia and industry due to their enormous potential in oral delivery of biomacromolecules.However,information on gastrointestinal lipolysis and trans-epithelial transport of SMEDDS is rare.Aggregation-caused quenching(ACQ)fuorescent probes are utilized to visualize the in vivo behaviors of SMEDDSs,because the released probes during lipolysis are quenched upon contacting water.Two SMEDDSs composed of medium chain triglyceride and different ratios of Tween-80 and PEG-400 are set as models,meanwhile Neoral?was used as a control.The SMEDDS droplets reside in the digestive tract for as long as 24 h and obey frst order kinetic law of lipolysis.The increased chain length of the triglyceride decreases the lipolysis of the SMEDDSs.Ex vivo imaging of main tissues and histological examination confrm the trans-epithelial transportation of the SMEDDS droplets.Approximately 2%-4%of the given SMEDDSs are transported via the lymph route following epithelial uptake,while liver is the main termination.Caco-2 cell lines confrm the cellular uptake and trans-epithelial transport.In conclusion,a fraction of SMEDDSs can survive the lipolysis in the gastrointestinal tract,permeate across the epithelia,translocate via the lymph,and accumulate mainly in the liver.展开更多
Whey protein isolate coated astaxanthin-loaded liposomes were prepared in this work.The gastrointestinal digestive fate of whey protein isolate coated astaxanthin-loaded liposomes was evaluated in terms of particle si...Whey protein isolate coated astaxanthin-loaded liposomes were prepared in this work.The gastrointestinal digestive fate of whey protein isolate coated astaxanthin-loaded liposomes was evaluated in terms of particle size,size distribution,zeta potential,and morphology during in vitro digestion as a function of time.Analysis on the particle size and morphology of whey protein isolate coated astaxanthin-loaded liposomes showed that the majority of particles maintained spherical shape with a progressive increase of particle size after passage through the digestion.The zeta potential on whey protein isolate coated astaxanthin-loaded liposomes became highly negative after digestion.As compared in uncoated liposomes,the astaxanthin release in whey protein isolate coated liposomes was slower in simulated gastric fluid digestion,while was faster in simulated intestinal fluid digestion.Through in vitro digestion,the bioaccessibility of astaxanthin was improved significantly after whey protein isolate coating.It was also found that the whey protein isolate coating could protect liposomes against destruction and suppress the lateral mobility of pyrene,resulting in lower micropolarity and fluidity of liposomal membrane during the digestion.These findings may guide the potential application of whey protein isolate coated liposomes for improving the bioaccessibility and stability of astaxanthin in nutraceuticals and pharmaceutics.展开更多
Laser lipolysis can effectively treat obesity and its associated diseases, such as hypertension, fatty liver, and hyperlipidemia. However, currently available invasive laser lipolysis, which transmits laser to a fiber...Laser lipolysis can effectively treat obesity and its associated diseases, such as hypertension, fatty liver, and hyperlipidemia. However, currently available invasive laser lipolysis, which transmits laser to a fiber-optic catheter inserted into the subcutaneous tissue for irradiation through an incision, may cause hematomas, infections, and empyrosis. The current study presents a novel, noninvasive approach for laser lipolysis, which directly irradiates the intact skin surface without an incision and preferentially targets adipose tissue at the near-infrared band. High laser energy is necessary to damage adipocytes; however, this may carbonate and burn the dermis. Therefore, the introduction of skin cooling is essential to avoid unwanted hyperthermal injury and improve the threshold of radiant exposure. In the current study, we investigated a novel noninvasive approach assisted with skin cooling by establishing a homogeneous multi-layer skin model. In this method, light propagation in the skin was simulated by using the Monte Carlo method. Skin cooling was employed before laser irradiation to protect the epidermis from thermal damage, which was treated as a boundary condition based on Newton's law. The numerical results showed that the photons were deposited in the adipose layer more than in the other layers. Laser can effectively destroy adipose tissue at an energy density of >200 J/cm^2 at 1210 nm wavelength, whereas at least 300 J/cm^2 is required at 1064 nm to achieve the same effect. In this experiment, at >5 s pulse width, the selectivity of adipose was not obvious. Moreover, the results indicated that 60 ms R134a or R404a spray can effectively reduce the temperature of the epidermis. R404a exhibited a stronger cooling effect than R134a. Cold air cooling at -10 °C for 10 s could effectively decrease the skin temperature, and deeper cooling could be achieved by cold air cooling compared with cryogen spray cooling.展开更多
Docosahexaenoic acid(DHA)is a biologically active fatty acid that reduces the accumulation of lipids.However,the molecular mechanism underlying this process,particularly in fish,is not well understood.Recent studies s...Docosahexaenoic acid(DHA)is a biologically active fatty acid that reduces the accumulation of lipids.However,the molecular mechanism underlying this process,particularly in fish,is not well understood.Recent studies show that endoplasmic reticulum(ER)stress triggers the activation of the unfolded protein response,which has been revealed to play an essential role in lipid metabolism.In this study,we explored the effect of DHA on ER stress and investigated the potential molecular mechanisms underlying DHA-induced adipocyte lipolysis in grass carp(Ctenopharyngodon idella)both in vivo and in vitro.We found that DHA remarkably reduced the triglyceride content,increased the secretion of glycerol,pro-moted lipolysis in adipocytes and evoked ER stress,whereas inhibiting ER stress using 4-phenyl butyric acid(4-PBA)inhibited the effects of DHA(P<0.05).These results implied that ER stress potentially participates in DHA-induced adipocyte lipolysis.Additionally,STF-083010,a specific inositol-requiring enzyme 1a(IRE1a)-inhibitor,attenuated the effects of DHA on lipolysis,demonstrating that IRE1a and X-box binding protein 1 potentially participate in DHA-induced lipolysis.DHA also activated the cyclic adenosine monophosphate(cAMP)-dependent protein kinase A(PKA)pathway by increasing the level of cAMP and activating the PKA enzyme(P<0.05).Nevertheless,H89,a PKA inhibitor,weakened DHA-induced lipolysis by inhibiting the cAMP/PKA signaling pathway.Furthermore,inhibiting ER stress us-ing 4-PBA also inhibited lipolysis and alleviated DHA-induced activation of the cAMP/PKA signaling pathway,suggesting that ER stress may participate in DHA-induced lipolysis through the activation of the cAMP/PKA signaling pathway.Our data illustrate that DHA supplementation can be a promising nutritional strategy for ameliorating lipid accumulation in grass carp.The present study elucidated the molecular mechanism for DHA-induced lipolysis in grass carp adipocytes and emphasized the impor-tance of ER stress and the cAMP/PKA pathway in DHA-induced lipolysis.These results deepen our un-derstanding of ameliorating lipids deposition in freshwater fish by targeting DHA.展开更多
The in vitro digestion models mimicking the gastrointestinal(GI)tract of general population and lipid indigestion patients(with lower levels of bile salts or pancreatic lipase)were selected to investigate whether diac...The in vitro digestion models mimicking the gastrointestinal(GI)tract of general population and lipid indigestion patients(with lower levels of bile salts or pancreatic lipase)were selected to investigate whether diacylglycerols(DAGs)are potential good lipid sources for these patients.Linseed oil-based DAG(LD)and linseed oil(LT)were selected.LD-based emulsion((83.74±1.23)%)had higher lipolysis degree than LT-based emulsion((74.47±1.16)%)when monitoring the GI tract of normal population as previously reported.Indigestion conditions seriously decreased the digestive degree of LT-based emulsion((40.23±2.48)%-(66.50±3.70)%)while showed less influence on LD-based emulsion((64.18±2.41)%-(81.85±3.45)%).As opposed to LT-based emulsion,LD-based emulsion exhibited preference for releasing unsaturated fatty acids(especially oleic acid andα-linolenic acid)due to their different glycerolipid compositions.LD-based emulsion showed potential for providing lipids and nutrients(including essential fatty acids)for lipid indigestion patients.展开更多
Chronic alcohol consumption induces hepatic steatosis, the early stage of alcoholic liver disease （ALD）. The aim ofpresent study is to investigate the protective effect ofPanax notoginseng saponins （PNS） against c...Chronic alcohol consumption induces hepatic steatosis, the early stage of alcoholic liver disease （ALD）. The aim ofpresent study is to investigate the protective effect ofPanax notoginseng saponins （PNS） against chronic ethanol-induced hepaticsteatosis in vivo. Mice were pair-fed a modified Lieber-DeCarli liquid diet containing alcohol or isocaloric maltose dextrin ascontrol diet with or without PNS （200 mg/kg, BW） for 8 weeks. Animals supplemented with PNS were protected against hepaticlipid accumulation induced by chronic ethanol exposure. Accordingly, PNS could significantly decrease the elevation of plasmatriglyceride, plasma enzyme activities, i.e. alanine aminotransferase （ALT） and aspartate aminotransferase （AST）, and hepaticTNF-ct and IL-6 levels which were induced by chronic alcohol exposure. In addition, PNS markedly reduced the lipolysis ofwhite adipose tissue （WAT） that stimulated by alcohol feeding through the inhibiting protein expression of phosphorylation ofhormone-sensitive lipase （p-HSL）, rather than total HSL. Furthermore, alcohol exposure also enhanced fatty acid uptake capacityin liver by elevated hepatic CD36 expression, which could attenuated by PNS treatment. These results demonstrate that PNSsupplementation protects against chronic ethanol-induced hepatic steatosis, which is associated with ameliorating dysfunctionallipid metabolism of WAT and the reduced inflammatory cytokines. Our findings suggested that PNS might be potential to bedeveloped as an effective agent for the treatment of chronic alcoholic steatosis.展开更多
基金funded by the Science and Technology Committee of Shanghai Municipality (Nos.19430741400, 23S11901500,23ZR1413100, and 21430760800)the National Natural Science Foundation of China (Nos.81973247 and 82030107)。
文摘Lipid-based nanocarriers have staged a remarkable comeback in the oral delivery of proteins and peptides, but delivery efficiency is compromised by lipolysis. β-Lactoglobulin(β-lg) stabilized lipid nanoparticles, including nanoemulsions(NE@β-lg) and nanocapsules(NC@β-lg), were developed to enhance the oral absorption of insulin by slowing down lipolysis due to the protection from β-lg. Cremophor EL stabilized nanoemulsions(NE@Cre-EL) were prepared and set as a control. The lipid nanoparticles produced mild and sustained hypoglycemic effects, amounting to oral bioavailability of 3.0% ± 0.3%, 7.0% ± 1.1%, and7.7% ± 0.8% for NE@Cre-EL, NE@β-lg, and NC@β-lg, respectively. Aggregation-caused quenching(ACQ)probes enabled the identification of intact nanoparticles, which were used to investigate the in vivo and intracellular fates of the lipid nanoparticles. In vitro digestion/lipolysis and ex vivo imaging confirmed delayed lipolysis from β-lg stabilized lipid nanoparticles. NC@β-lg was more resistant to intestinal lipolysis than NE@β-lg due to the Ca^(2+)-induced crosslinking. Live imaging revealed the transepithelial transport of intact nanoparticles and their accumulation in the liver. Cellular studies confirmed the uptake of intact nanoparticles. Slowing down lipolysis via food proteins represents a good strategy to enhance the oral absorption of lipid nanoparticles and thus co-formulated biomacromolecules.
基金supported by the Yili Industrial Group Co., Ltd., and National Natural Science Foundation of China (81973042).
文摘Probiotics crosstalk immunity to improve host glycolipid metabolism,which is a new strategy for obesity.This study aimed to explore the functions of Lacticaseibacillus paracasei K56(K56),in regulating the lipid metabolism of adipocytes and its immune regulation mechanisms.We co-cultured RAW264.7 macrophages with K56,and the K56-stimulated RAW264.7-conditioned medium(K56-CM)was collected and treated with 3T3-L1 pre-adipocytes.The expression of lipid metabolism-related markers of adipocytes,and the content of cytokines in CMs were detected.The results demonstrated that K56-CM promoted the expression of peroxisome proliferator-activated receptor-γ(PPAR-γ),CCAAT/enhancer binding proteinα(C/EBPα),and other adipogenesis-related markers,which resulted in the upregulation of lipolysis markers,such as hormone-sensitive lipase(HSL),adipose triglyceride lipase(ATGL).The activation of lipolysis enhanced the expression of fatty acidβ-oxidation-related and mitochondrial biogenesis-related markers and reduced lipid accumulation in adipocytes.The glycolipid metabolism pattern of K56 may be due to its immunomodulatory characteristics,which stimulated macrophages to secrete fewer TNF-α,thereby promoting the expression of lipolysis-related markers,and TNF-αsynergized with lipase to promote lipolysis.It has not been reported that L.paracasei modulated lipid metabolism via the lipolysis pathway,which suggested that K56 may regulate glycolipid metabolism of the host by maintaining immune homeostasis.
基金funded by the Michigan Animal Agricultural Alliance competitive project#AA-23–0014United States Department of Agriculture National Institute of Food and Agriculture(USDA)projects#2019–67015-29443 and#2021–67037-34657+2 种基金the United States-Israel Binational Agricultural Research Development(BARD)Fund project#IS-5167–19the Office for the Associate Dean of Research at Michigan State Universitysupported by USDA National Institute of Food and Agriculture’s Agriculture and Food Research Initiative Educational Workforce and Development Program award#2024-67011-42947。
文摘Background As cows transition from pregnancy to lactation,free fatty acids(FFA)are mobilized from adipose tissues(AT)through lipolysis to counter energy deficits.In clinically healthy cows,lipolysis intensity is reduced throughout lactation;however,if F FA release exceeds tissue demands or the liver's metabolic capacity,lipid byproducts accumulate,incre a sing cows'risk of metabolic and infectious disease.Endocannabinoids(eCBs)and their congeners,N-acylethanolamines(NAEs),are lipid-based compounds that modulate metabolism and inflammation.Their synthesis and release depend upon the availability of FFA precursors and the abundance of synthesizing and degrading enzymes and transporters.Therefore,we hypothesized that eCB production and transcription of endocannabinoid system components are modulated by lipolysis pathways in adipocytes.To test this hypothesise we stimulated canonical(isoproterenol,1μmol/L;ISO)and inflammatory(lipopolysaccharide,1μg/m L;LPS)lipolysis pathways in adipocytes isolated from the AT of 5 Holstein dairy cows.Following,we assessed lipolysis intensity,adipocytes'release of eCBs,and transcription of endocannabinoid system components.Results We found that ISO and LPS stimulated lipolysis at comparable intensities.Exposure to either treatment tended to elevate the release of eCBs and NAEs by cultured adipocytes;however,specific eCBs and NAEs and the transcriptional profiles differed by treatment.On one hand,ISO enhanced adipocytes'release of 2-arachidonoylglycerol(2-AG)but reduced NAE production.Klotably,ISO enhanced the cells"expression of enzymes associated with 2-AG biosynthesis(INPP5F,GDPD5,GPAT4),transport(CD36),and adipogenesis(PPARG).Conversely,LPS enhanced adipocytes'synthesis and release of N-arachidonoylethanolamide(AEA).This change coincided with enhanced transcription of the NAE-biosynthesizing enzyme,PTPN22,and adipocytes'transcription of genes related to eCB degradation(PTGS2,MGLL,CYP27B1).Furthermore,LPS enhanced adipocytes'transcription of eCB and NAE transporters(HSPA1A,SCP2)and the expression of the anti-adipogenic ion channel,TRPV3.Conclusions Our data provide evidence for distinct modulatory roles of canonical and inflammatory lipolysis pathways over eCB release and transcriptional regulation of biosynthesis,degradation,transport,and ECS signaling in cows'adipocytes.Based on our findings,we conclude that,within adipocytes,eCB production and ECS component expression are,at least in part,mediated by lipolysis in a pathway-dependent manner.These findings contribute to a deeper understanding of the molecular mechanisms underlying metabolic regulation in dairy cows'AT,with potential implications for prevention and treatment of inflammatory and metabolic disorders.
基金Supported by grant from National Natural Science Foundation (39870362)Natural Science Foundation of Education Committee of Jiangsu Province (98KJB320002).
文摘Objective: To investigate the influence of central administration ofneuropeptide Y-Y5 receptor antisense oligodeoxynucleotides (ODNs) on body weight, fat pads of SDrats, and the effects of white adipocytes lipolysis and apoptosis. Methods: Y5 receptor antisense,sense, mismatched ODNs or vehicle was intracerebroventricularly (i. c. v.) injected. Averageadipocyte area was calculated. DNA ladders were measured to evaluate adipocyte apoptosis, and RT-PCRwas used to analyse the expression of Bcl-2 and Bax gene. Results: Central administration of Y5antisense ODNs significantly decreased body weight, and average adipocyte area. DNA fragmentationwas present after electrophoresis at epididymal adipose tissue. The expression of Bcl-2 gene wasdownregulated, while the expression of Bax upregulated. Conclusion: Lipolysis and adipocyteapoptosis may be important mechanisms far 75 antisense therapy.
基金supported by National Natural Science Foundation of China(Grant No.21171011 and 21671009)
文摘Insulin resistance is characterized as one of crucial pathological changes in type 2 diabetes mellitus（T2DM）, and dyslipidaemia is frequently detected in T2DM. A variety of vanadium compounds have been studied as drug candidates for diabetes based on their insulin-like action. However, few studies focus on their antilipolytic effect. In the present study, we established an insulin-resistant model in 3T3-L1 adipocytes to mimic pathological conditions of T2DM according to a well-established method by the treatment of high concentrations of glucose and insulin, which was validated by oil red O staining and the decreased levels of phosphorylated Akt, AS160 and GSK3 after insulin treatment. The results demonstrated that bis（acetylacetonato）-oxidovanadium（Ⅳ）（VO（acac）_2） could inhibit isoproterenol-stimulated lipolysis through the reduction of the phosphorylated HSL and perilipin levels in both insulin-sensitive and insulin-resistant 3T3-L1 adipocytes. Moreover, although the levels of phosphorylated Akt induced by VO（acac）_2 were decreased, the rates of lipolytic inhibition were not significantly altered compared with those under insulin-sensitive condition, indicating that the anti-lipolytic effect of VO（acac）_2 might also function in an Akt-independent way in insulin-resistant adipocytes. Our work here help elucidate the anti-diabetic effects of vanadium compounds. It may not only shed light on the utility of vanadium-based compounds as potential anti-diabetic drugs but also serve as a useful screening model for new anti-diabetic drugs.
基金supported in part by USDA-NIFA(Washington,DC)grants 2014-68004-21972 and 2015-67015-23207Department of Large Animal Clinical Sciences(East Lansing,MI)+2 种基金the Michigan State University Elwood Kirkpatrick Dairy Science Research Endowment(East Lansing,MI)Michigan Alliance for Animal Agriculture(East Lansing,Michigan)Michigan Animal Health Foundation
文摘Elevated concentrations of plasma fatty acids in transition dairy cows are significantly associated with increased disease susceptibility and poor lactation performance. The main source of plasma fatty acids throughout the transition period is lipolysis from adipose tissue depots. During this time, plasma fatty acids serve as a source of calories mitigating the negative energy balance prompted by copious milk synthesis and limited dry matter intake.Past research has demonstrated that lipolysis in the adipose organ is a complex process that includes not only the activation of lipolytic pathways in response to neural, hormonal, or paracrine stimuli, but also important changes in the structure and cellular distribution of the tissue in a process known as adipose tissue remodeling. This process involves an inflammatory response with immune cell migration, proliferation of the cellular components of the stromal vascular fraction, and changes in the extracellular matrix. This review summarizes current knowledge on lipolysis in dairy cattle, expands on the new field of adipose tissue remodeling, and discusses how these biological processes affect transition cow health and productivity.
基金National Natural Science Foundation of China(Grant No.20871008 and 21171011)
文摘In the present study, we investigated the role of reactive oxygen species（ROS） elevation induced by an anti-diabetic vanadium compound, vanadyl acetylacetonate（VO（acac）2）, in the regulation of lipolysis and glucose metabolism using differentiated 3T3L1 adipocytes as a model system. By confocal laser scanning microscopy, we found that VO（acac）2 induced ROS generation under high glucose stimulation, and the pretreatment of NADPH oxidase inhibitors could significantly reduce the elevated ROS level. Meanwhile, the decreased phosphorylated levels of AKT and the two key modulators of lipolysis（HSL and perilipin） were observed by western blot analysis. We also found that the contents of glycerol release were further reduced as well. In addition, the levels of key regulatory proteins, AS160 and GSK3β, in glucose metabolism pathway were correspondingly reduced. These findings demonstrated that ROS induced by vanadium compounds could act as a metabolic signal to activate AKT pathway to inhibit lipolysis and promote glucose transport and glycogen synthesis rather than by direct action by themselves. Our study contributed to elucidate the anti-diabetic effects of vanadium compounds and provided a theoretical basis for the further development of new vanadium complexes in the prevention and therapeutics of diabetes.
文摘Hatchery-roared juvenile black sea breams are characterized by a low level of highly unsaturated fatty acids in their bodies, as compared with wild fish. To assess the effect of docosahaxaenoic acid （DHA） on lipegenic and lipelysis enzymes, one-year fish were roared on a casein-based purified diet and a DHA fortified diet （ 1.5% DHA ethyl ester/kg diet） for 60 d, followed with a period of 55 d for starvation. Dietary DHA was effectively incorporated into the fish body. Fortification of DHA depressed activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase as lipogenic enzymes in the hepatopancroas and intraperitoneal fat body. Carnitine palmitoyltransferase as lipolysis enzyme in the hepatopancreas was active in the DHA fortified fish. Starvation after feeding experiment induced increased carnitine palmitoyltransferase activity in both control and DHA fortified fish and the activity remained higher in the DHA fortified fish, while the monoenes were selectively consumed prior to highly unsaturated fatty acids. These results indicated that dietary DHA depressed lipogenesis and activated lipolysis.
基金This study was financially supported by National Key R&D Program of China(grant No.2017YFD0400105)Natural Science Foundation of Beijing Municipality(grant No.6192009)Fengtai science and technology new star(grant No.KJXX201902).
文摘The effect of sodium chloride(NaCl)curing salt content on protein oxidation,lipid oxidation and lipolysis of Chinese dry sausage was investigated.Two groups Chinese dry sausages with 2%and 4%(m/m)salt content were studied.The degree of protein oxidation increased during the processes in two groups sausages,while the content of phospholipids decreased,neutral lipids and free fatty acids increased.The degree of protein oxidation,lipid oxidation and lipolysis in 4%NaCl content group was higher than those in 2%NaCl content group,while 4%NaCl content group has higher lipase activity.In conclusion,4%NaCl may facilitate the protein oxidation,lipid hydrolysis and oxidation in Chinese dry sausage,and the protein oxidation had strong correlation with lipid oxidation and lipolysis.The results could provide a basis for improving the technology of industrial production.
基金supported by the National Key R&D Program of China(Nos.2018YFC1704500 and 2018YFC 1704503)the National Natural Science Foundation of China(Nos.82074080 and 81773877)the Natural Science Foundation of Jiangsu Province(No.BK20181328).
文摘Simiao Wan(SMW)is a traditional Chinese formula,including Atractylodis Rhizoma,Achyranthis Bidentatae Radix,Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2.It can be used to the treatment of diabetes.However,its bioactive compounds and underlying mechanism are unclear.This study was designed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance.Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activity was screened in fasted mice.The effects of 60%ethanol elution(ESMW)on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid(PA)and high fat diet(HFD)-fed mice.In our study,ESMW was the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS.ESMW suppressed protein kinase A(PKA)-hormone-sensitive lipase(HSL)related lipolysis and increased AMP-activated protein kinase(AMPK)phosphorylation in PA challenged 3T3-L1 adipocytes.AMPKa knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660,revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent.Furthermore,ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice.It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis.Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells,demonstrating that the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production.In conclusion,ESMW,as the antilipolytic fraction of SMW,inhibited PKA-HSL related lipolysis by activating AMPK,inhibiting diacylglycerol(DAG)accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.
基金supported by the Technology Development Program for Agriculture and Forestry, Ministry for Agriculture, Forestiy and Fisheries, Republic of Korea
文摘OBJECTIVE： Traditional Korean Chungtaejeon （CTJ） tea is a type of fermented tea, which has received increasing attention in recent years because of its purported health benefits. The present study was designed to investigate the effect and mechanism of CTJ tea extract on body weight gain using C57BL/6J-Lep ob/ob mice and 3T3-L1 adipocytes, respectively. METHODS： The effects of CTJ on cell viability, lipid accumulation, and expression of protein and mRNA were measured in 3T3-L1 adipocytes by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, oil red O staining, Western blotting, and reverse transcriptase-polymerase chain reaction analyses. C57BL6J-Lep ob/ob mice were administered with CTJ （200 or 400 mg/kg body weight） for ten weeks. Then, body weight, food intake, total cholesterol, and triglyceride were measured in ob/ob mice. RESULTS： CTJ tea extract treated at 250 wg/mL （CTJ250） significantly suppressed lipid accumulation in the differentiated 3T3-L1 adipocytes. Likewise, CTJ250 significantly decreased the protein expression of peroxisome proliferator-activated receptor Y （PPARy）, CCJ^u~,T/enhancer-binding protein a, and adipocyte lipid- binding protein, and regulated the mRNA expression of PPART, sterol regulatory element-binding protein- lc gene, fatty acid synthase, adipocyte lipid-binding protein, hormone-sensitive lipase, carnitine palmitoyl transferase 1, cluster of differentiation 36, and acetyl-CoA carboxylase in the differentiated 3T3-L1 adipocytes. Mice administered with CTJ showed dose-dependent decrease in body weight gain, starting from week 4 of the experiment. CTJ tea extract administered at 400 mg/kg body weight significantly decreased fat mass, food efficacy ratio, and levels of plasma triglyceride and total cholesterol. CONCLUSION： CTJ attenuated weight gain in ob/ob mice and regulated the activity of the molecules involved in adipogenesis and lipolysis in 3T3-L1 adipocytes. CTJ is a potentially valuable herbal therapy for the prevention of obesity and/or obesity-related disorders.
基金the National Natural Science Foundation of China(Nos.61973211,51911540479 and M-0221)the Research Project of Institute of Medical Robotics of Shanghai Jiao Tong Universitythe Project of Science and Technology Commission of Shanghai Municipality(No.20DZ2220400)。
文摘With many advantages such as non-invasive,safe and quick effect,focused ultrasound lipolysis stands out among many fat-removing methods.However,during the whole process,the doctor needs to hold the ultrasound transducer and press it on the patient’s skin with a large pressure for a long time;thus the probability of muscle and bone damage for doctors is greatly increased.To reduce the occurrence of doctors’occupational diseases,a depth camera-based ultrasonic lipolysis robot system is proposed to realize robot-assisted automatic ultrasonic lipolysis operation.The system is composed of RealSense depth camera,KUKA LBR Med seven-axis robotic arm,PC host,and ultrasonic lipolysis instrument.The whole operation includes two parts:preoperative planning and intraoperative operation.In preoperative planning,the treatment area is selected in the camera image by the doctor;then the system automatically plans uniformly distributed treatment points in the treatment area.At the same time,the skin normal vector is calculated to determine the end posture of the robot,so that the ultrasound transducer can be pressed down in the normal direction of skin.During the intraoperative operation,the robot is controlled to arrive at the treatment point in turn.Meanwhile,the patient’s movement can be detected by the depth camera,and the path of robot is adjusted in real time so that the robot can track the movement of patient,thereby ensuring the accuracy of the ultrasonic lipolysis operation.Finally,the human body model experiment is conducted.The results show that the maximum error of the robot operation is within 5mm,average error is 3.1mm,and the treatment points of the robot operation are more uniform than those of manual operation.Therefore,the system can replace the doctor and achieve autonomous ultrasonic lipolysis to reduce the doctor’s labor intensity.
基金This work was graciously supported by the Chinese National Natural Science Foundation(Grant 31901725 and 32201933)the Science and Technology Projects in Guangzhou(Grant 202201010170).
文摘Vaccarin,a flavonoid glycoside isolated from Vaccaria segetalis,is non-toxic to 3T3-L1 cells up to concentrations of 200μM.Accordingly,we investigated the effects of this natural product on adipogenesis and lipolysis in 3T3-L1 adipocytes.Our results revealed that vaccarin significantly inhibited lipid accumulation by suppressing the adipogenesis-related transcription factors peroxisome proliferator-activated receptorγ(PPARγ)and the CCAAT/enhancer-binding proteinα(C/EBPα).Specifically,lipid accumulation decreased by up to 27.7±2.7%when 3T3-L1 adipocytes were treated with a 10μM concentration of vaccarin.Mechanistic studies showed that the compound inhibited adipogenesis through activation of the Hedgehog(Hh)signaling pathway and so restoring Smo and Gli1 expression at an early stage of differentiation.In mature 3T3-L1 cells,vaccarin significantly increased the secretion of glycerol into the surrounding medium and thus indicating that it accelerated the degradation of triglycerides.In addition,vaccarin,was shown to enhance lipolysis through stimulation of the transcription levels of lipoprotein lipase,monoglycerides lipase,adipose triacylglyceride lipase,hormone-sensitive lipase and adipose differentiated-related protein.All told,vaccarin suppressed lipid accumulation and enhanced lipolysis during adipocyte differentiation by restoring Hh signaling.As such,it is a phytochemical capable of halting adipocyte hyperplasia and,thereby,ameliorating the effects of obesity.
基金supported by the Basic Research Project of Yunnan Provincial Science and Technology Department(202201AT070262)the Project of Yunnan Province Food and Drug Homologous Resources Functional Food Innovation Team(A3032023057)+1 种基金the Yunnan Province Ten Thousand Plan Industrial Technology Talents Project(YNWR-CYJS-2020-010)the Yunnan Province-City Integration Project(202302 AN360002).
文摘Obesity has brought great challenges to global human health,and how to effectively prevent and control the occurrence and development of obesity has become an urgent problem.The role and mechanism of 4-[(α-Lrhamnosyloxy)benzyl]isothiocyanate(MITC),an active ingredient of Moringa oleifera Lam.,in the regulation of lipid metabolism have not been comprehensively investigated.In the present study,we investigated the mechanism of MITC in inhibiting lipid accumulation in mice fed with a high-fat diet(HFD)in terms of both lipolysis and central appetite regulation mediated by the gut microbe-gut-brain axis.MITC enhanced the characteristic indices associated with HFD mice and also promoted adipocytolysis and brown fat thermogenesis.Moreover,MITC was observed to improve leptin resistance,modulate the composition of gut microbiota such as Ruminococcaceae,Parasutterella,and Acetatifactor,promote 5-hydroxytryptamine secretion,further enhance the secretion of glucagon-like peptide-1(GLP-1)and peptide tyrosine-tyrosine(PYY)to activate peroxisome proliferator-activated receptor(PPAR)signaling in the hypothalamus,and modulate feeding behavior to inhibit lipid accumulation in HFD mice.These data suggest that MITC supplementation can help to alleviate obesity or obesity-related diseases.
基金supported by the National Natural Science Foundation of China(Nos.82030107,81973247,81872815,81872826,and 81690263)Science and Technology Commission of Shanghai Municipality(Nos.19XD1400300,19430741400,and 19410761200,China)。
文摘Self-microemulsifying drug delivery systems(SMEDDSs)have recently returned to the limelight of academia and industry due to their enormous potential in oral delivery of biomacromolecules.However,information on gastrointestinal lipolysis and trans-epithelial transport of SMEDDS is rare.Aggregation-caused quenching(ACQ)fuorescent probes are utilized to visualize the in vivo behaviors of SMEDDSs,because the released probes during lipolysis are quenched upon contacting water.Two SMEDDSs composed of medium chain triglyceride and different ratios of Tween-80 and PEG-400 are set as models,meanwhile Neoral?was used as a control.The SMEDDS droplets reside in the digestive tract for as long as 24 h and obey frst order kinetic law of lipolysis.The increased chain length of the triglyceride decreases the lipolysis of the SMEDDSs.Ex vivo imaging of main tissues and histological examination confrm the trans-epithelial transportation of the SMEDDS droplets.Approximately 2%-4%of the given SMEDDSs are transported via the lymph route following epithelial uptake,while liver is the main termination.Caco-2 cell lines confrm the cellular uptake and trans-epithelial transport.In conclusion,a fraction of SMEDDSs can survive the lipolysis in the gastrointestinal tract,permeate across the epithelia,translocate via the lymph,and accumulate mainly in the liver.
基金financially supported by National Natural Science Foundation of China(32001738)the Key Scientific Research Projects of Higher Education Institutions of Henan Province in China(21A550006)+3 种基金Natural Science Innovation Fund Support Plan of Henan University of Technology(2020ZKCJ13)Young Backbone Teacher Cultivation Program of Henan University of Technology,High-level Talents Fund of Henan University of Technology(2018BS049)Key Scientific and Technological Project of Henan Province(202102310006)National Innovation and Entrepreneurship Training Program for College Students(202010463003).
文摘Whey protein isolate coated astaxanthin-loaded liposomes were prepared in this work.The gastrointestinal digestive fate of whey protein isolate coated astaxanthin-loaded liposomes was evaluated in terms of particle size,size distribution,zeta potential,and morphology during in vitro digestion as a function of time.Analysis on the particle size and morphology of whey protein isolate coated astaxanthin-loaded liposomes showed that the majority of particles maintained spherical shape with a progressive increase of particle size after passage through the digestion.The zeta potential on whey protein isolate coated astaxanthin-loaded liposomes became highly negative after digestion.As compared in uncoated liposomes,the astaxanthin release in whey protein isolate coated liposomes was slower in simulated gastric fluid digestion,while was faster in simulated intestinal fluid digestion.Through in vitro digestion,the bioaccessibility of astaxanthin was improved significantly after whey protein isolate coating.It was also found that the whey protein isolate coating could protect liposomes against destruction and suppress the lateral mobility of pyrene,resulting in lower micropolarity and fluidity of liposomal membrane during the digestion.These findings may guide the potential application of whey protein isolate coated liposomes for improving the bioaccessibility and stability of astaxanthin in nutraceuticals and pharmaceutics.
基金financially supported by the National Natural Science Foundation of China (Grant No.51336006 and 51727811)
文摘Laser lipolysis can effectively treat obesity and its associated diseases, such as hypertension, fatty liver, and hyperlipidemia. However, currently available invasive laser lipolysis, which transmits laser to a fiber-optic catheter inserted into the subcutaneous tissue for irradiation through an incision, may cause hematomas, infections, and empyrosis. The current study presents a novel, noninvasive approach for laser lipolysis, which directly irradiates the intact skin surface without an incision and preferentially targets adipose tissue at the near-infrared band. High laser energy is necessary to damage adipocytes; however, this may carbonate and burn the dermis. Therefore, the introduction of skin cooling is essential to avoid unwanted hyperthermal injury and improve the threshold of radiant exposure. In the current study, we investigated a novel noninvasive approach assisted with skin cooling by establishing a homogeneous multi-layer skin model. In this method, light propagation in the skin was simulated by using the Monte Carlo method. Skin cooling was employed before laser irradiation to protect the epidermis from thermal damage, which was treated as a boundary condition based on Newton's law. The numerical results showed that the photons were deposited in the adipose layer more than in the other layers. Laser can effectively destroy adipose tissue at an energy density of >200 J/cm^2 at 1210 nm wavelength, whereas at least 300 J/cm^2 is required at 1064 nm to achieve the same effect. In this experiment, at >5 s pulse width, the selectivity of adipose was not obvious. Moreover, the results indicated that 60 ms R134a or R404a spray can effectively reduce the temperature of the epidermis. R404a exhibited a stronger cooling effect than R134a. Cold air cooling at -10 °C for 10 s could effectively decrease the skin temperature, and deeper cooling could be achieved by cold air cooling compared with cryogen spray cooling.
基金supported by the National Nature Science Foundation of China(NSFC,Grant Number:31772863,32072989).
文摘Docosahexaenoic acid(DHA)is a biologically active fatty acid that reduces the accumulation of lipids.However,the molecular mechanism underlying this process,particularly in fish,is not well understood.Recent studies show that endoplasmic reticulum(ER)stress triggers the activation of the unfolded protein response,which has been revealed to play an essential role in lipid metabolism.In this study,we explored the effect of DHA on ER stress and investigated the potential molecular mechanisms underlying DHA-induced adipocyte lipolysis in grass carp(Ctenopharyngodon idella)both in vivo and in vitro.We found that DHA remarkably reduced the triglyceride content,increased the secretion of glycerol,pro-moted lipolysis in adipocytes and evoked ER stress,whereas inhibiting ER stress using 4-phenyl butyric acid(4-PBA)inhibited the effects of DHA(P<0.05).These results implied that ER stress potentially participates in DHA-induced adipocyte lipolysis.Additionally,STF-083010,a specific inositol-requiring enzyme 1a(IRE1a)-inhibitor,attenuated the effects of DHA on lipolysis,demonstrating that IRE1a and X-box binding protein 1 potentially participate in DHA-induced lipolysis.DHA also activated the cyclic adenosine monophosphate(cAMP)-dependent protein kinase A(PKA)pathway by increasing the level of cAMP and activating the PKA enzyme(P<0.05).Nevertheless,H89,a PKA inhibitor,weakened DHA-induced lipolysis by inhibiting the cAMP/PKA signaling pathway.Furthermore,inhibiting ER stress us-ing 4-PBA also inhibited lipolysis and alleviated DHA-induced activation of the cAMP/PKA signaling pathway,suggesting that ER stress may participate in DHA-induced lipolysis through the activation of the cAMP/PKA signaling pathway.Our data illustrate that DHA supplementation can be a promising nutritional strategy for ameliorating lipid accumulation in grass carp.The present study elucidated the molecular mechanism for DHA-induced lipolysis in grass carp adipocytes and emphasized the impor-tance of ER stress and the cAMP/PKA pathway in DHA-induced lipolysis.These results deepen our un-derstanding of ameliorating lipids deposition in freshwater fish by targeting DHA.
基金National Key R&D Program of China(2022YFC2805100)National Science Fund for Key Program of National Natural Science Foundation of China(31930084)+3 种基金National Science Fund for Distinguished Young Scholars of China(31725022)China Agriculture Research System(CARS-18-ZJ0503)Guangdong Provincial Key R&D Programme(2022B0202010002)Science and Technology Innovation Project of Foshan City(FS0AAKJ919-4402-0013)。
文摘The in vitro digestion models mimicking the gastrointestinal(GI)tract of general population and lipid indigestion patients(with lower levels of bile salts or pancreatic lipase)were selected to investigate whether diacylglycerols(DAGs)are potential good lipid sources for these patients.Linseed oil-based DAG(LD)and linseed oil(LT)were selected.LD-based emulsion((83.74±1.23)%)had higher lipolysis degree than LT-based emulsion((74.47±1.16)%)when monitoring the GI tract of normal population as previously reported.Indigestion conditions seriously decreased the digestive degree of LT-based emulsion((40.23±2.48)%-(66.50±3.70)%)while showed less influence on LD-based emulsion((64.18±2.41)%-(81.85±3.45)%).As opposed to LT-based emulsion,LD-based emulsion exhibited preference for releasing unsaturated fatty acids(especially oleic acid andα-linolenic acid)due to their different glycerolipid compositions.LD-based emulsion showed potential for providing lipids and nutrients(including essential fatty acids)for lipid indigestion patients.
基金Research Committee of the University of Macao(Grant No.MYRG123-ICMS12 and MYRG111-ICMS13)from Macao Science and Technology Development Fund(Grant No.010/2013/A1)
文摘Chronic alcohol consumption induces hepatic steatosis, the early stage of alcoholic liver disease （ALD）. The aim ofpresent study is to investigate the protective effect ofPanax notoginseng saponins （PNS） against chronic ethanol-induced hepaticsteatosis in vivo. Mice were pair-fed a modified Lieber-DeCarli liquid diet containing alcohol or isocaloric maltose dextrin ascontrol diet with or without PNS （200 mg/kg, BW） for 8 weeks. Animals supplemented with PNS were protected against hepaticlipid accumulation induced by chronic ethanol exposure. Accordingly, PNS could significantly decrease the elevation of plasmatriglyceride, plasma enzyme activities, i.e. alanine aminotransferase （ALT） and aspartate aminotransferase （AST）, and hepaticTNF-ct and IL-6 levels which were induced by chronic alcohol exposure. In addition, PNS markedly reduced the lipolysis ofwhite adipose tissue （WAT） that stimulated by alcohol feeding through the inhibiting protein expression of phosphorylation ofhormone-sensitive lipase （p-HSL）, rather than total HSL. Furthermore, alcohol exposure also enhanced fatty acid uptake capacityin liver by elevated hepatic CD36 expression, which could attenuated by PNS treatment. These results demonstrate that PNSsupplementation protects against chronic ethanol-induced hepatic steatosis, which is associated with ameliorating dysfunctionallipid metabolism of WAT and the reduced inflammatory cytokines. Our findings suggested that PNS might be potential to bedeveloped as an effective agent for the treatment of chronic alcoholic steatosis.
