Background Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns.This pathological overaccumulation results from complex metabolic d...Background Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns.This pathological overaccumulation results from complex metabolic dysregulation across multiple organs.While current research largely centers on adipogenesis within adipose tissue,a comprehensive understanding of the cross-organ regulatory factors influencing this process remains elusive.Results Here,we employed a high-fat diet(HFD)model and multi-omics approaches to investigate cross-organ regulatory mechanisms underlying abdominal fat deposition in broilers.Our results demonstrated that HFD not only promoted fat accumulation but also altered meat quality traits.Through 16S rRNA amplicon sequencing,we identified significant gut microbiota dysbiosis in HFD-fed chickens,manifested by an increased abundance of Lactobacillus and a decreased abundance of Enterococcus.However,jejunal microbiota transplantation from HFD donors did not induce abdominal fat deposition in recipient chickens.Metabolomic profiling revealed that HFD elevated the level of succinic acid,a metabolite positively correlated with Lactobacillus abundance and potentially generated by Lactobacillus.This increase in succinic acid(SA)further triggered metabolic inflammation response in both jejunal tissue and serum.In vivo validation established succinic acid as a key inflammatory mediator facilitating HFD-induced cross-organ communication between the jejunum and abdominal adipose tissue,enhancing intestinal lipid uptake and subsequent abdominal fat deposition.Bulk and single-nucleus RNA sequencing(snRNA-seq)revealed that HFD induced macrophage population expansion and intensified adipocyte-macrophage crosstalk.Adipocyte-macrophage co-culture systems further elucidated that macrophages are an indispensable factor in succinic acid-induced fat deposition.Conclusion This study delineates a succinic acid-driven"gut-fat axis"governing abdominal fat deposition in broilers,integrating gut microbiota dysbiosis and macrophage-mediated inflammatory adipogenesis.By identifying succinic acid as a cross-organ signaling molecule that enhances lipid absorption and activates macrophage-dependent adipogenesis,we establish systemic metabolic-immune crosstalk as a pivotal regulatory mechanism.These findings redefine fat deposition as a process extending beyond adipose-centric models,advancing multi-omics-guided strategies for sustainable poultry production.展开更多
The gut microbiota has emerged as a pivotal regulator of host lipid metabolism and energy homeostasis.A growing body of evidence reveals that variations in the composition and metabolic activity of intestinal microbes...The gut microbiota has emerged as a pivotal regulator of host lipid metabolism and energy homeostasis.A growing body of evidence reveals that variations in the composition and metabolic activity of intestinal microbes are closely associated with differences in adipose tissue deposition across species.Notably,increased abundance of Firmicutes and a reduced proportion of Bacteroidetes and butyrate-producing bacteria have been linked to enhanced fat accumulation.Key microbial metabolites such as short-chain fatty acids(SCFAs)influence lipid metabolism through multiple pathways,including the activation of GPR41/43 receptors,modulation of the bile acid–FXR/TGR5 axis,and regulation of hepatic lipogenesis.Additionally,the gut–brain axis plays a critical role in controlling feeding behavior via neuroendocrine signaling.This review summarizes current advances in understanding the roles of dominant bacterial phyla and beneficial genera—including Clostridium butyricum and Faecalibacterium prausnitzii—in fat metabolism.We further explore the mechanisms by which gut microbiota modulate lipid synthesis and catabolism through SCFA production,bile acid signaling,and AMPK/PPAR-related pathways.These insights highlight the potential of microbiota-targeted strategies to restore lipid metabolic balance,offering novel opportunities for applications in health management,nutritional interventions,and microbial therapeutics.展开更多
Cultured meat provides a sustainable and safe alternative to traditional meat production by culturing animal cells in vitro.Cultured fat is an important component of cultured meat,contributing to its flavor,texture,an...Cultured meat provides a sustainable and safe alternative to traditional meat production by culturing animal cells in vitro.Cultured fat is an important component of cultured meat,contributing to its flavor,texture,and nutrition.Induced adipogenic differentiation is the most important step in the production of cultured fat,but conventional adipogenic inducer cocktails are complex and contain non-food-grade substances,which introduces a food safety risk for cultured meat products.Here we demonstrated that a food-grade substance,peanut oil(P-OIL),promoted adipogenic differentiation and lipid accumulation of bovine adipose-derived stem cells,based on which a simple and efficient approach was developed to produce cultured bovine fat.Mechanistic analysis showed that P-OIL upregulated genes involved in lipid synthesis and storage,such as peroxisome proliferator-activated receptor y(PPARy),carnitine palmitoyltransferase 2,and lipoprotein lipase,by activating the PPAR signaling pathway during adipogenesis.Notably,the lipid composition of cultured bovine fats generated using P-OIL induction was similar to that of fats obtained from farmed cattle,but free of trans-fatty acids.This study provides valuable insights into the production of safe,healthy,and nutritious cultured fats.展开更多
Intramuscular fat(IMF)content serves as the key determinants of meat quality.Emerging evidence indicates that gut microbiota and their metabolites significantly influence IMF deposition levels by modulating host lipid...Intramuscular fat(IMF)content serves as the key determinants of meat quality.Emerging evidence indicates that gut microbiota and their metabolites significantly influence IMF deposition levels by modulating host lipid metabolism through multiple pathways,positioning microbial regulation as a pivotal target for meat quality improvement.However,existing studies remain fragmented,predominantly focusing on isolated mechanisms or correlations without a systematic view of the regulatory network.This review consolidates the core mechanisms through which microbiota-derived metabolites including short-chain fatty acids,bile acids,branched-chain amino acids,trimethylamine N-oxide,tryptophan derivatives,succinate,polyamines etc.,regulate IMF deposition and proposes a targeted intervention framework,the“gut microbiota/metabolites-IMF axis”.By integrating these insights,we provide a theoretical foundation and define practical research pathways to assess the potential of microbial-based strategies for improving meat quality in swine production.展开更多
Objective The rising prevalence of childhood obesity is closely associated with suboptimal dietary patterns.To address this public health concern,we conducted a comprehensive study to examine the association between c...Objective The rising prevalence of childhood obesity is closely associated with suboptimal dietary patterns.To address this public health concern,we conducted a comprehensive study to examine the association between coarse cereals consumption and body fat percentage(BFP)in Chinese children and adolescents.Methods The study included 48,305 children aged 6–17 years from 28 districts/counties in 14 provinces across seven regions of China(24,152 girls and 24,153 boys).BFP was examined using bioelectrical impedance analysis in the early morning.Coarse cereals consumption was assessed using a Food Frequency Questionnaire and categorized into three groups:0 g/1,000 kcal per day,0–10 g/1,000kcal per day,and>10 g/1,000 kcal per day(daily consumption of coarse cereals×1,000/total energy consumption).Quantile regression model was used to analyze the association between coarse cereals and BFP,adjusting for potential confounders such as age,pubertal development stage,urban/rural and regional factors,total daily dietary energy consumption,sedentary time,moderate-to-high physical activity,household income,parental education,and consumption of other foods.Results Boys aged 6–10,11–14,and 15–17 years had median daily coarse cereals consumptions of6.6 g,7.1 g,and 5.7 g,with BFP of 19.6%,19.5%,and 17.5%(all P<0.05).Girls in the same age groups showed consumption of 7.1 g,8.4 g,and 6.7 g,with BFP of 20.3%,26.4%,and 31.0%(all P<0.05).The quantile regression results for boys showed that daily consumption of coarse cereals was significantly correlated with their BFP in the 0.15,0.25,and 0.50 quartiles,with regression coefficients of-0.257,-0.221,and-0.330,respectively,after adjusting for potential confounders(P<0.05).For girls,there was a significant correlation with PBF at the 0.05,0.15,0.25,0.50,0.75,and 0.85 quartiles,with regression coefficients of-0.258,-0.366,-0.372,-0.431,-0.472,and-0.503(P<0.05 for all).Conclusions Coarse cereals consumption among Chinese children and adolescents remains relatively low.Higher consumption was inversely associated with BFP in children aged 6–17 years.Future interventional studies should assess how increased coarse cereals consumption prevents childhood obesity.展开更多
Background Fast-growing broilers are poorly adapted to heat.Adjusting feed composition may mitigate heat stress(HS)effects in temperate climates,while maintaining performance and health during cooler days.Methods One ...Background Fast-growing broilers are poorly adapted to heat.Adjusting feed composition may mitigate heat stress(HS)effects in temperate climates,while maintaining performance and health during cooler days.Methods One thousand nine hundred and twenty Ross 308 male broilers were housed in 64 pens in 4 climate-controlled rooms,2 under cyclical HS(d 28–43;32±2℃;60%–70%RH;09:30–15:30)and 2 under thermoneutral(TN)conditions.In the finisher phase,broilers were allocated to 4 dietary treatments,analyzed values are given except for metabolizable energy(ME):low crude protein(CP)and control fat(LowCP-ConF;17.0%CP,5.9%crude fat(CF),2,925 kcal/kg ME),low CP and high fat(LowCP-HighF;17.2%CP,7.9%CF,3,019 kcal/kg ME),control CP and high fat(ConCP-HighF;18.1%CP,8.0%CF,2,992 kcal/kg ME)and a basal control(ConCP-ConF;18.7%CP,6.3%CF,2,913 kcal/kg ME).LowCP diets contained control levels of digestible amino acids.Results During the finisher phase,compared to control CP levels,LowCP increased average daily feed intake(ADFI)(+2.15%;P=0.020)and affected average daily gain(ADG)and feed conversion ratio(FCR)negatively under TN(-3.77%and+6.49%;P=0.003 and P<0.001,respectively),but not during HS.Compared to control CF,HighF decreased ADFI during TN and HS(-3.16%and-3.17%;P<0.001 and P=0.022)and reduced ADG in TN groups(-3.17%;P=0.010),but not during HS.Mortality was higher in broilers receiving HighF during HS(P=0.040).Slaughter weights were unaffected.LowCP decreased plasma uric acid and lactate dehydrogenase levels during TN,but increased plasma glucose during HS.LowCP increased breast meat redness(a*)during TN and HS(P<0.05).HighF decreased fat(-1.68%;P=0.017),but increased protein levels(+1.53%;P<0.001)in breast meat of HS-broilers.Conclusion LowCP and HighF impaired performance under TN but not under HS.HighF increased mortality under HS,yet improved breast meat composition.These findings highlight the challenge of designing an optimal diet for both conditions and underscore the need to better understand amino acid needs and energy-to-protein ratios during HS.展开更多
Background The role of bile acids in modulating the gut microbiota and their impact on host metabolism has garnered significant attention.Taurochenodeoxycholic acid(TCDCA)is the predominant bile acid within the chicke...Background The role of bile acids in modulating the gut microbiota and their impact on host metabolism has garnered significant attention.Taurochenodeoxycholic acid(TCDCA)is the predominant bile acid within the chicken bile acid pool and is closely related to metabolic disorders.The current study aims to investigate the potential effects of TCDCA on abdominal fat deposition in broilers.From 14 to 28 days of age,the broilers in the CON group received an oral administration of 1 mL of saline,while those in the treatment groups were administered 1 mL of a solution containing 0.05 g,0.10 g,or 0.20 g of TCDCA.Results The results showed that TCDCA treatments from 14 to 28 d had no significant effects on BW,ADFI,ADG and FCR in broilers at the age of 28 days of age.However,the abdominal fat percentage in the 0.20 g TCDCA group significantly increased,accompanied by higher TBA and HDL-c levels,as well as a reduction in apolipoprotein B levels in serum.In addition,serum triglyceride levels tended to be higher in the 0.20 g TCDCA group(P=0.098).The 0.20 g TCDCA treatment increased the gene expressions of SREBP-1,C/EBP-α,and ELOVL6,while decreasing the mRNA abundance of ATGL and CPT-1 in the abdominal fat.Serum levels of TCDCA,TDCA,and THDCA were significantly higher after 0.20 g TCDCA administration,while TCA levels were significantly lower,as determined by the targeted bile acid metabolomics analysis.Conversely,hepatic mRNA levels of CYP7A1,CYP27A1,BAAT,and BSEP were increased in the 0.20 g TCDCA group.The oral administration of 0.20 g TCDCA also upregulated the expression of FXR,VDR,and FGF19 in abdominal fat.The 16S rRNA analysis of cecal microbiota revealed that a decrease in the Shannon and Simpson indexes in the 0.20 g TCDCA group,and an increase in the Firmicutes/Bacteroidetes ratio.LEfSe analysis revealed that the predominant bacteria in the CON group were Streptococcus and Oscillospira at the genus level,while Lactobacillus,Parabacteroides,Anaeroplasma,and Helicobacter were identified as the dominant genera in the 0.20 g TCDCA group.Functional predictions for the gut microbiota exhibited that lipid metabolism,replication and repair pathway were enhanced in the 0.20 g TCDCA group.Correlation analysis demonstrated that the abundance of Lactobacillus was positively correlated with serum levels of TCDCA,THDCA,and TDCA,while the abundance of Streptococcus and Oscillospira showed a positive correlation with serum TCA levels.Conclusion Overall,this study elucidates that the intervention of 0.20 g TCDCA may promote abdominal fat deposition by activating bile acid receptors in abdominal fat,and concurrent alterations in both the intestinal microbial community and bile acid profile.展开更多
Purpose:This study examined potential differences in strength,muscle morphology,and motor unit(MU)behavior of the abductor digiti minimi(ADM)between normal-fat(NF)and over-fat(OF)males.Methods:Dual-energy X-ray absorp...Purpose:This study examined potential differences in strength,muscle morphology,and motor unit(MU)behavior of the abductor digiti minimi(ADM)between normal-fat(NF)and over-fat(OF)males.Methods:Dual-energy X-ray absorptiometry assessed percent body fat(%BF).Ultrasonography determined muscle cross-sectional area(CSA),echo intensity(EI),and subcutaneous fat(s FAT).MU behavior was assessed during isometric muscle actions at 50%of maximal voluntary contraction(MVC)by analyzing the y-intercepts and slopes for the MU action potential amplitude(MUAPAMP)vs.recruitment threshold(RT)relationships,the A and B terms for the mean firing rate(MFR)vs.RT relationships,and normalized electromyographic amplitude(N-EMGRMS).MU firing times and waveforms were validated with reconstruct-and-test and spike trigger average procedures.Results:%BF was greater for OF(25.70%±5.40%)than NF(16.50%±2.20%;p<0.001).MVC was greater for NF(27.13±7.16)N than OF([19.89±4.96]N;p=0.014).CSA was greater for NF(2.48±0.39)cm^(2)than OF([1.95±0.47]cm^(2);p=0.011).The y-intercepts for the MUAPAMPvs.RT relationships were greater for NF(0.283±0.254)m V than OF([-0.221±0.659]m V;p=0.004).The B terms for the MFR vs.RT relationships were greater for NF(-0.024±0.003)pps/%MVC than OF([-0.031±0.009]pps/%MVC;p=0.038).N-EMGRMSwas similar between groups(p=0.463).Conclusion:Maximal strength,muscle size,and MU recruitment and firing rate patterns for a non-weight bearing muscle differed between normal-fat and over-fat males.展开更多
Background Goat milk is increasingly recognized for high digestibility and a distinctive compositional profile.Protein acetylation,an important post-translational modification,regulates biosynthetic and metabolic path...Background Goat milk is increasingly recognized for high digestibility and a distinctive compositional profile.Protein acetylation,an important post-translational modification,regulates biosynthetic and metabolic pathways.This study aimed to identify critical acetylated proteins and specific modification sites involved in milk production and component synthesis in dairy goats,thereby elucidating the molecular mechanisms of lactation.We performed a comparative TMT-based acetylomic and proteomic analysis of mammary tissues from Saanen dairy goats during peak lactation and the dry period using LC–MS/MS.A candidate acetylation site was further investigated in goat mammary epithelial cells(GMECs)through site-directed mutagenesis and lipid metabolic assays,establishing functional links between acetylation and mammary lipid metabolism and providing a foundation for molecular strategies to improve milk quality and yield.Results We established a comprehensive mammary acetylome,identifying 862 significantly acetylated proteins and 2,028 modification sites across the two physiological phases.Differentially acetylated proteins were predominantly localized to the cytoplasm(39.98%).From these,54 key acetylated proteins,including MTOR,BCAT2,QARS1,GOT1,GOT2,BDH1,ACSS1,STAT5B,FABP5,and GPAM were prioritized as candidates involved in milk protein synthesis,milk fat synthesis,lactose synthesis,and other lactation-related processes.Among them,β-hydroxybutyrate dehydrogenase 1(BDH1)acetylation was characterized in detail.Members of the HDAC family were identified as primary regulators mediating BDH1 deacetylation.BDH1 acetylation promoted lipid droplet formation and triglyceride synthesis in GMECs.At the transcriptional level,BDH1 acetylation upregulated LXRα,ACSL1 and SCD1,whereas deacetylation downregulated SCD1,FASN,and ACSL1.Notably,BDH1 acetylation/deacetylation significantly reduced SREBP1 expression,linking this modification to coordinated control of lipogenic gene networks.Conclusions This study established,for the first time,the comprehensive acetylome of mammary gland tissues in dairy goats,revealing a substantial number of differentially acetylated proteins and modification sites.We demonstrate that acetylation of BDH1 regulated by HDACs promotes lipid droplet biogenesis and triglyceride synthesis in GMECs through transcriptional modulation of key lipogenic genes and suppression of SREBP1.These findings provide mechanistic insights into the post-translational regulation of mammary lipid metabolism and offer molecular targets for future genetic and nutritional strategies aimed at enhancing milk quality and yield in dairy goats.展开更多
Objective Previous studies link lower body mass index(BMI)with increased obsessive-compulsive disorder(OCD)risk,yet other body mass indicators may be more etioloically relevant.We dissected the causal association betw...Objective Previous studies link lower body mass index(BMI)with increased obsessive-compulsive disorder(OCD)risk,yet other body mass indicators may be more etioloically relevant.We dissected the causal association between body fat mass(FM)and OCD.Methods Summary statistics from genome-wide association studies of European ancestry were utilized to conduct two-sample Mendelian randomization analysis.Heterogeneity,horizontal pleiotropy,and sensitivity analyses were performed to assess the robustness.Results The inverse variance weighting method demonstrated that a genetically predicted decrease in FM was causally associated with an increased OCD risk[odds ratio(OR)=0.680,95%confidence interval(CI):0.528–0.875,P=0.003].Similar estimates were obtained using the weighted median approach(OR=0.633,95%CI:0.438–0.915,P=0.015).Each standard deviation increases in genetically predicted body fat percentage corresponded to a reduced OCD risk(OR=0.638,95%CI:0.455–0.896,P=0.009).The sensitivity analysis confirmed the robustness of these findings with no outlier instrument variables identified.Conclusion The negative causal association between FM and the risk of OCD suggests that the prevention or treatment of mental disorders should include not only the control of BMI but also fat distribution and body composition.展开更多
Overweight and obesity has been a major public health problem globally.It was estimated that more than 2.1 billion adults were affected by overweight or obese in 2021 worldwide,about one fifth of whom lived in China^(...Overweight and obesity has been a major public health problem globally.It was estimated that more than 2.1 billion adults were affected by overweight or obese in 2021 worldwide,about one fifth of whom lived in China^([1]).By 2050,the country is forecast to remain the one with the largest population of overweight and obese globally^([1]),if no effective strategies were applied on overweight/obesity control.展开更多
Type 1 diabetes(T1D)is defined by autoimmune-mediated destruction of the insulin-producing pancreatic β-cells.Impaired insulin secretion due to β-cell apoptosis and islet massloss is the main feature of T1D[1].Curre...Type 1 diabetes(T1D)is defined by autoimmune-mediated destruction of the insulin-producing pancreatic β-cells.Impaired insulin secretion due to β-cell apoptosis and islet massloss is the main feature of T1D[1].Current therapeutic strategies for T1D are mainly through subcutaneous administration of insulin or islet/pancreas transplantation.展开更多
The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiqui...The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiquitous in the immune response of the central nervous system.The fat mass and obesity-related protein catalyzes the demethylation of N^(6)-methyladenosine modifications on mRNA and is widely expressed in various tissues,participating in the regulation of multiple diseases’biological processes.However,the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear.In this study,we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model.After fat mass and obesity interference,BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b^(+)/CD86^(+)cells and the secretion of pro-inflammatory cytokines.Fat mass and obesity-mediated N^(6)-methyladenosine demethylation accelerated the degradation of ADAM17 mRNA,while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA.Therefore,down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia.These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N^(6)-methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.展开更多
Intrapancreatic fat deposition(IPFD)has garnered increasing attention in recent years.The prevalence of IPFD is relatively high and associated with factors such as obesity,age,and sex.However,the pathophysiological me...Intrapancreatic fat deposition(IPFD)has garnered increasing attention in recent years.The prevalence of IPFD is relatively high and associated with factors such as obesity,age,and sex.However,the pathophysiological mechanisms underlying IPFD remain unclear,with several potential contributing factors,including oxida-tive stress,alterations in the gut microbiota,and hormonal imbalances.IPFD was found to be highly correlated with the occurrence and prognosis of exocrine pan-creatic diseases.Although imaging techniques remain the primary diagnostic approach for IPFD,an expanding array of biomarkers and clinical scoring systems have been identified for screening purposes.Currently,effective treatments for IPFD are not available;however,existing medications,such as glucagon-like peptide-1 receptor agonists,and new therapeutic approaches explored in animal models have shown considerable potential for managing this disease.This paper reviews the pathogenesis of IPFD,its association with exocrine pancreatic disea-ses,and recent advancements in its diagnosis and treatment,emphasizing the significant clinical relevance of IPFD.展开更多
Intramuscular fat(IMF)is an important economic trait for pork quality,affecting meat flavour,juiciness,and tenderness.Hence,the improvement of IMF content is one of the hotspots of animal science to provide better mea...Intramuscular fat(IMF)is an important economic trait for pork quality,affecting meat flavour,juiciness,and tenderness.Hence,the improvement of IMF content is one of the hotspots of animal science to provide better meat product.Here,we found that most IMF-related genes are enriched in lipid metabolism processes,including fatty acid transport and uptake,fatty acid beta oxidation,lipid synthesis,lipid storage,and lipolysis.PPAR and AMPK signalling pathways are identified to be responsible for IMF deposition.Genetics and nongenetic factors(i.e.,diets,gut microbiota,age,sex and management)also positively or negatively regulate the IMF content in pigs.Taken together,this review deepens our understanding of how these factors affect pig IMF deposition and provides valuable information for moderately increasing IMF content.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disea-se.The accuracy of noninvasive biomarkers for detecting hepatic steatosis is still limited.AIM To assess the diagnostic performa...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disea-se.The accuracy of noninvasive biomarkers for detecting hepatic steatosis is still limited.AIM To assess the diagnostic performance of noninvasive steatosis biomarkers in diag-nosing NAFLD using magnetic resonance imaging proton density fat fraction(MRI-PDFF)as the gold standard.METHODS A total of 131 suspected NAFLD patients(60%male,median age 36 years)under-going MRI-PDFF were consecutively recruited from a tertiary hospital.Steatosis grades determined by MRI-PDFF were classified as none(<5%),mild(5%-11%),moderate(11%-17%),and severe(≥17%).Six steatosis biomarkers were calculated according to clinical parameters and laboratory tests,including fatty liver index,hepatic steatosis index,ZJU index,Framingham steatosis index,triglycerides and glucose index,and visceral adiposity index.The accuracy of these biomarkers in detecting hepatic steatosis was evaluated using the area under the receiver operating characteristic curves(AUCs).The Youden index was used to determine the optimal cut-off for each biomarker.The linear trend analysis of each biomarker across the steatosis grades was conducted by Mantel-Haenszelχ2 test.Spearman's rank correlation assessed the relationship between steatosis biomarkers and MRI-PDFF.RESULTS Steatosis grades based on MRI-PDFF prevalence were:None 27%,mild 40%,moderate 15%and severe 18%.Six steatosis biomarkers showed a linear trend across the steatosis grades and a significant positive correlation with MRI-PDFF.The six steatosis biomarkers demonstrated AUCs near 0.90(range:0.857-0.912,all P<0.001)for diagnosing NAFLD by MRI-PDFF≥5%.The optimal cut-offs showed sensitivity between 84.4%-91.7%and specificity between 71.4%-85.7%.The diagnostic performance of these biomarkers in detecting moderate-to-severe and severe steatosis was relatively weaker.CONCLUSION These noninvasive steatosis biomarkers accurately diagnosed NAFLD and correlated well with MRI-PDFF for detecting NAFLD,but they did not effectively detect moderate or severe steatosis.展开更多
In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).C...In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract,influenced by genetic predisposition,gut microbiota dysbiosis,and environmental factors.Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD.Further,visceral adipose tissue,particularly creeping fat,a mesenteric adipose tissue characterized by hypertrophy and fibrosis,has been implicated in CD pathogenesis,inflammation,and fibrosis.The bacteria from the gut microbiota may translocate into mesenteric adipose tissue,contributing to the formation of creeping fat and influencing CD progression.Although creeping fat may be a protective barrier against bacterial invasion,its expansion can damage adjacent tissues,leading to complications.Modulating gut microbiota through interventions such as fecal microbiota transplantation,probiotics,and prebiotics has shown potential in managing CD.However,more research is needed to clarify the mechanisms linking gut dysbiosis,creeping fat,and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.展开更多
Background Intramuscular fat is an important factor in evaluating pork quality and varies widely among different pig breeds.However,the regulatory mechanism of circular RNAs(circRNAs)in lipid metabolism remains largel...Background Intramuscular fat is an important factor in evaluating pork quality and varies widely among different pig breeds.However,the regulatory mechanism of circular RNAs(circRNAs)in lipid metabolism remains largely unexplored.Results We combined circRNA-seq and Ribo-seq data to screen a total of 18 circRNA candidates with coding potential,and circANKRD17 was found to be significantly elevated in the longissimus dorsi muscle of Lantang piglets,with a length of 1,844 nucleotides.Using single-cell sequencing,we identified 477 differentially expressed genes in IMF cells between Lantang and Landrace piglets,with enrichment in the PPAR signaling pathway.These genes included FABP4,FABP5,CPT1A,and UBC,consistent with the high levels of acylcarnitines observed in the longissimus dorsi muscles of the Lantang breed,as determined by lipidomic analysis.Further in vitro and in vivo experiments indicated that circANKRD17 can regulate lipid metabolism through various mechanisms involving the PPAR pathway,including promoting adipocyte differentiation,fatty acid transport and metabolism,triglyceride synthesis,and lipid droplet formation and maturation.In addition,we discovered that circANKRD17 has an open reading frame and can be translated into a novel 571-amino-acid protein that promotes lipid metabolism.Conclusions Our research provides new insights into the role of protein-coding circANKRD17,especially concerning the metabolic characteristics of pig breeds with higher intramuscular fat content.展开更多
BACKGROUND Ankylosing spondylitis(AS)is recognized as a long-term inflammatory disorder that leads to inflammation in the spine and joints,alongside abnormal bone growth.In previous studies,we reported that mesenchyma...BACKGROUND Ankylosing spondylitis(AS)is recognized as a long-term inflammatory disorder that leads to inflammation in the spine and joints,alongside abnormal bone growth.In previous studies,we reported that mesenchymal stem cells(MSCs)derived from individuals with AS demonstrated a remarkable inhibition in the formation of osteoclasts compared to those obtained from healthy donors.The mechanism through which MSCs from AS patients achieve this inhibition remains unclear.AIM To investigate the potential underlying mechanism by which MSCs from individuals with ankylosing spondylitis(AS-MSCs)inhibit osteoclastogenesis.METHODS We analysed fat mass and obesity-associated(FTO)protein levels in AS-MSCs and MSCs from healthy donors and investigated the effects and mechanism by which FTO in MSCs inhibits osteoclastogenesis by coculturing and measuring the levels of tartrate-resistant acid phosphatase,nuclear factor of activated T cells 1 and cathepsin K.RESULTS We found that FTO,an enzyme responsible for removing methyl groups from RNA,was more abundantly expressed in MSCs from AS patients than in those from healthy donors.Reducing FTO levels was shown to diminish the capacity of MSCs to inhibit osteoclast development.Further experimental results revealed that FTO affects the stability of the long non-coding RNA activated by DNA damage(NORAD)by altering its N6-methyladenosine methylation status.Deactivating NORAD in MSCs significantly increased osteoclast formation by affecting miR-4284,which could regulate the MSC-mediated inhibition of osteoclastogenesis reported in our previous research.CONCLUSION This study revealed elevated FTO levels in AS-MSCs and found that FTO regulated the ability of AS-MSCs to inhibit osteoclast formation through the long noncoding RNA NORAD/miR-4284 axis.展开更多
基金supported by the National Key Research and Development Program of China(2022YFF1000201)National Scientific Foundation of China(32272861)the China Agriculture Research System of MOF and MARA(CARS-41)。
文摘Background Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns.This pathological overaccumulation results from complex metabolic dysregulation across multiple organs.While current research largely centers on adipogenesis within adipose tissue,a comprehensive understanding of the cross-organ regulatory factors influencing this process remains elusive.Results Here,we employed a high-fat diet(HFD)model and multi-omics approaches to investigate cross-organ regulatory mechanisms underlying abdominal fat deposition in broilers.Our results demonstrated that HFD not only promoted fat accumulation but also altered meat quality traits.Through 16S rRNA amplicon sequencing,we identified significant gut microbiota dysbiosis in HFD-fed chickens,manifested by an increased abundance of Lactobacillus and a decreased abundance of Enterococcus.However,jejunal microbiota transplantation from HFD donors did not induce abdominal fat deposition in recipient chickens.Metabolomic profiling revealed that HFD elevated the level of succinic acid,a metabolite positively correlated with Lactobacillus abundance and potentially generated by Lactobacillus.This increase in succinic acid(SA)further triggered metabolic inflammation response in both jejunal tissue and serum.In vivo validation established succinic acid as a key inflammatory mediator facilitating HFD-induced cross-organ communication between the jejunum and abdominal adipose tissue,enhancing intestinal lipid uptake and subsequent abdominal fat deposition.Bulk and single-nucleus RNA sequencing(snRNA-seq)revealed that HFD induced macrophage population expansion and intensified adipocyte-macrophage crosstalk.Adipocyte-macrophage co-culture systems further elucidated that macrophages are an indispensable factor in succinic acid-induced fat deposition.Conclusion This study delineates a succinic acid-driven"gut-fat axis"governing abdominal fat deposition in broilers,integrating gut microbiota dysbiosis and macrophage-mediated inflammatory adipogenesis.By identifying succinic acid as a cross-organ signaling molecule that enhances lipid absorption and activates macrophage-dependent adipogenesis,we establish systemic metabolic-immune crosstalk as a pivotal regulatory mechanism.These findings redefine fat deposition as a process extending beyond adipose-centric models,advancing multi-omics-guided strategies for sustainable poultry production.
基金supported by National Key R&D Program of China(2024YFF1001500)Sichuan Science and Technology Program(2021YFYZ0007,2024NSFSC0298,SCCXTD-2025-8)+1 种基金China Agriculture Research System(CARS-35)National Natural Science Foundation of China(32421005)。
文摘The gut microbiota has emerged as a pivotal regulator of host lipid metabolism and energy homeostasis.A growing body of evidence reveals that variations in the composition and metabolic activity of intestinal microbes are closely associated with differences in adipose tissue deposition across species.Notably,increased abundance of Firmicutes and a reduced proportion of Bacteroidetes and butyrate-producing bacteria have been linked to enhanced fat accumulation.Key microbial metabolites such as short-chain fatty acids(SCFAs)influence lipid metabolism through multiple pathways,including the activation of GPR41/43 receptors,modulation of the bile acid–FXR/TGR5 axis,and regulation of hepatic lipogenesis.Additionally,the gut–brain axis plays a critical role in controlling feeding behavior via neuroendocrine signaling.This review summarizes current advances in understanding the roles of dominant bacterial phyla and beneficial genera—including Clostridium butyricum and Faecalibacterium prausnitzii—in fat metabolism.We further explore the mechanisms by which gut microbiota modulate lipid synthesis and catabolism through SCFA production,bile acid signaling,and AMPK/PPAR-related pathways.These insights highlight the potential of microbiota-targeted strategies to restore lipid metabolic balance,offering novel opportunities for applications in health management,nutritional interventions,and microbial therapeutics.
基金funded by the Agricultural Science and Technology Major Projectthe Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SN-ZJU-SIAS-0013)the Jiangsu Basic Research Center for Synthetic Biology(BK20233003)。
文摘Cultured meat provides a sustainable and safe alternative to traditional meat production by culturing animal cells in vitro.Cultured fat is an important component of cultured meat,contributing to its flavor,texture,and nutrition.Induced adipogenic differentiation is the most important step in the production of cultured fat,but conventional adipogenic inducer cocktails are complex and contain non-food-grade substances,which introduces a food safety risk for cultured meat products.Here we demonstrated that a food-grade substance,peanut oil(P-OIL),promoted adipogenic differentiation and lipid accumulation of bovine adipose-derived stem cells,based on which a simple and efficient approach was developed to produce cultured bovine fat.Mechanistic analysis showed that P-OIL upregulated genes involved in lipid synthesis and storage,such as peroxisome proliferator-activated receptor y(PPARy),carnitine palmitoyltransferase 2,and lipoprotein lipase,by activating the PPAR signaling pathway during adipogenesis.Notably,the lipid composition of cultured bovine fats generated using P-OIL induction was similar to that of fats obtained from farmed cattle,but free of trans-fatty acids.This study provides valuable insights into the production of safe,healthy,and nutritious cultured fats.
基金financially supported by the National Key Research and Development Program of China(2023YFD1301303)the National Natural Science Foundation of China(No.32202715)+1 种基金the National Natural Science Foundation of China(No.23DAA00403)Double first-class discipline promotion project under grant(No.2023B10564001)。
文摘Intramuscular fat(IMF)content serves as the key determinants of meat quality.Emerging evidence indicates that gut microbiota and their metabolites significantly influence IMF deposition levels by modulating host lipid metabolism through multiple pathways,positioning microbial regulation as a pivotal target for meat quality improvement.However,existing studies remain fragmented,predominantly focusing on isolated mechanisms or correlations without a systematic view of the regulatory network.This review consolidates the core mechanisms through which microbiota-derived metabolites including short-chain fatty acids,bile acids,branched-chain amino acids,trimethylamine N-oxide,tryptophan derivatives,succinate,polyamines etc.,regulate IMF deposition and proposes a targeted intervention framework,the“gut microbiota/metabolites-IMF axis”.By integrating these insights,we provide a theoretical foundation and define practical research pathways to assess the potential of microbial-based strategies for improving meat quality in swine production.
基金supported by the Special Project of National Science and Technology Basic Resources Survey(Grant No.2017FY101100)。
文摘Objective The rising prevalence of childhood obesity is closely associated with suboptimal dietary patterns.To address this public health concern,we conducted a comprehensive study to examine the association between coarse cereals consumption and body fat percentage(BFP)in Chinese children and adolescents.Methods The study included 48,305 children aged 6–17 years from 28 districts/counties in 14 provinces across seven regions of China(24,152 girls and 24,153 boys).BFP was examined using bioelectrical impedance analysis in the early morning.Coarse cereals consumption was assessed using a Food Frequency Questionnaire and categorized into three groups:0 g/1,000 kcal per day,0–10 g/1,000kcal per day,and>10 g/1,000 kcal per day(daily consumption of coarse cereals×1,000/total energy consumption).Quantile regression model was used to analyze the association between coarse cereals and BFP,adjusting for potential confounders such as age,pubertal development stage,urban/rural and regional factors,total daily dietary energy consumption,sedentary time,moderate-to-high physical activity,household income,parental education,and consumption of other foods.Results Boys aged 6–10,11–14,and 15–17 years had median daily coarse cereals consumptions of6.6 g,7.1 g,and 5.7 g,with BFP of 19.6%,19.5%,and 17.5%(all P<0.05).Girls in the same age groups showed consumption of 7.1 g,8.4 g,and 6.7 g,with BFP of 20.3%,26.4%,and 31.0%(all P<0.05).The quantile regression results for boys showed that daily consumption of coarse cereals was significantly correlated with their BFP in the 0.15,0.25,and 0.50 quartiles,with regression coefficients of-0.257,-0.221,and-0.330,respectively,after adjusting for potential confounders(P<0.05).For girls,there was a significant correlation with PBF at the 0.05,0.15,0.25,0.50,0.75,and 0.85 quartiles,with regression coefficients of-0.258,-0.366,-0.372,-0.431,-0.472,and-0.503(P<0.05 for all).Conclusions Coarse cereals consumption among Chinese children and adolescents remains relatively low.Higher consumption was inversely associated with BFP in children aged 6–17 years.Future interventional studies should assess how increased coarse cereals consumption prevents childhood obesity.
基金funded by VLAIO(Flemish Innovation&Entrepreneurship),grant number HBC.2020.3165。
文摘Background Fast-growing broilers are poorly adapted to heat.Adjusting feed composition may mitigate heat stress(HS)effects in temperate climates,while maintaining performance and health during cooler days.Methods One thousand nine hundred and twenty Ross 308 male broilers were housed in 64 pens in 4 climate-controlled rooms,2 under cyclical HS(d 28–43;32±2℃;60%–70%RH;09:30–15:30)and 2 under thermoneutral(TN)conditions.In the finisher phase,broilers were allocated to 4 dietary treatments,analyzed values are given except for metabolizable energy(ME):low crude protein(CP)and control fat(LowCP-ConF;17.0%CP,5.9%crude fat(CF),2,925 kcal/kg ME),low CP and high fat(LowCP-HighF;17.2%CP,7.9%CF,3,019 kcal/kg ME),control CP and high fat(ConCP-HighF;18.1%CP,8.0%CF,2,992 kcal/kg ME)and a basal control(ConCP-ConF;18.7%CP,6.3%CF,2,913 kcal/kg ME).LowCP diets contained control levels of digestible amino acids.Results During the finisher phase,compared to control CP levels,LowCP increased average daily feed intake(ADFI)(+2.15%;P=0.020)and affected average daily gain(ADG)and feed conversion ratio(FCR)negatively under TN(-3.77%and+6.49%;P=0.003 and P<0.001,respectively),but not during HS.Compared to control CF,HighF decreased ADFI during TN and HS(-3.16%and-3.17%;P<0.001 and P=0.022)and reduced ADG in TN groups(-3.17%;P=0.010),but not during HS.Mortality was higher in broilers receiving HighF during HS(P=0.040).Slaughter weights were unaffected.LowCP decreased plasma uric acid and lactate dehydrogenase levels during TN,but increased plasma glucose during HS.LowCP increased breast meat redness(a*)during TN and HS(P<0.05).HighF decreased fat(-1.68%;P=0.017),but increased protein levels(+1.53%;P<0.001)in breast meat of HS-broilers.Conclusion LowCP and HighF impaired performance under TN but not under HS.HighF increased mortality under HS,yet improved breast meat composition.These findings highlight the challenge of designing an optimal diet for both conditions and underscore the need to better understand amino acid needs and energy-to-protein ratios during HS.
基金funded by the National Key Research&Development Program of China(2023YFD1301400 and 2023YFF1001900)the Program for Shaanxi Science&Technology(2022GD-TSLD-46-0302,2023KXJ-243,2023GXJS-02-01 and L2022-QCYZX-NY-004)。
文摘Background The role of bile acids in modulating the gut microbiota and their impact on host metabolism has garnered significant attention.Taurochenodeoxycholic acid(TCDCA)is the predominant bile acid within the chicken bile acid pool and is closely related to metabolic disorders.The current study aims to investigate the potential effects of TCDCA on abdominal fat deposition in broilers.From 14 to 28 days of age,the broilers in the CON group received an oral administration of 1 mL of saline,while those in the treatment groups were administered 1 mL of a solution containing 0.05 g,0.10 g,or 0.20 g of TCDCA.Results The results showed that TCDCA treatments from 14 to 28 d had no significant effects on BW,ADFI,ADG and FCR in broilers at the age of 28 days of age.However,the abdominal fat percentage in the 0.20 g TCDCA group significantly increased,accompanied by higher TBA and HDL-c levels,as well as a reduction in apolipoprotein B levels in serum.In addition,serum triglyceride levels tended to be higher in the 0.20 g TCDCA group(P=0.098).The 0.20 g TCDCA treatment increased the gene expressions of SREBP-1,C/EBP-α,and ELOVL6,while decreasing the mRNA abundance of ATGL and CPT-1 in the abdominal fat.Serum levels of TCDCA,TDCA,and THDCA were significantly higher after 0.20 g TCDCA administration,while TCA levels were significantly lower,as determined by the targeted bile acid metabolomics analysis.Conversely,hepatic mRNA levels of CYP7A1,CYP27A1,BAAT,and BSEP were increased in the 0.20 g TCDCA group.The oral administration of 0.20 g TCDCA also upregulated the expression of FXR,VDR,and FGF19 in abdominal fat.The 16S rRNA analysis of cecal microbiota revealed that a decrease in the Shannon and Simpson indexes in the 0.20 g TCDCA group,and an increase in the Firmicutes/Bacteroidetes ratio.LEfSe analysis revealed that the predominant bacteria in the CON group were Streptococcus and Oscillospira at the genus level,while Lactobacillus,Parabacteroides,Anaeroplasma,and Helicobacter were identified as the dominant genera in the 0.20 g TCDCA group.Functional predictions for the gut microbiota exhibited that lipid metabolism,replication and repair pathway were enhanced in the 0.20 g TCDCA group.Correlation analysis demonstrated that the abundance of Lactobacillus was positively correlated with serum levels of TCDCA,THDCA,and TDCA,while the abundance of Streptococcus and Oscillospira showed a positive correlation with serum TCA levels.Conclusion Overall,this study elucidates that the intervention of 0.20 g TCDCA may promote abdominal fat deposition by activating bile acid receptors in abdominal fat,and concurrent alterations in both the intestinal microbial community and bile acid profile.
文摘Purpose:This study examined potential differences in strength,muscle morphology,and motor unit(MU)behavior of the abductor digiti minimi(ADM)between normal-fat(NF)and over-fat(OF)males.Methods:Dual-energy X-ray absorptiometry assessed percent body fat(%BF).Ultrasonography determined muscle cross-sectional area(CSA),echo intensity(EI),and subcutaneous fat(s FAT).MU behavior was assessed during isometric muscle actions at 50%of maximal voluntary contraction(MVC)by analyzing the y-intercepts and slopes for the MU action potential amplitude(MUAPAMP)vs.recruitment threshold(RT)relationships,the A and B terms for the mean firing rate(MFR)vs.RT relationships,and normalized electromyographic amplitude(N-EMGRMS).MU firing times and waveforms were validated with reconstruct-and-test and spike trigger average procedures.Results:%BF was greater for OF(25.70%±5.40%)than NF(16.50%±2.20%;p<0.001).MVC was greater for NF(27.13±7.16)N than OF([19.89±4.96]N;p=0.014).CSA was greater for NF(2.48±0.39)cm^(2)than OF([1.95±0.47]cm^(2);p=0.011).The y-intercepts for the MUAPAMPvs.RT relationships were greater for NF(0.283±0.254)m V than OF([-0.221±0.659]m V;p=0.004).The B terms for the MFR vs.RT relationships were greater for NF(-0.024±0.003)pps/%MVC than OF([-0.031±0.009]pps/%MVC;p=0.038).N-EMGRMSwas similar between groups(p=0.463).Conclusion:Maximal strength,muscle size,and MU recruitment and firing rate patterns for a non-weight bearing muscle differed between normal-fat and over-fat males.
基金supported by the National Key Research and Development Program of China(2022YFF1000102)Xi’an Agricultural Technology Research General Project(24NYGG0025)the National Natural Science Foundation of China(31702098)。
文摘Background Goat milk is increasingly recognized for high digestibility and a distinctive compositional profile.Protein acetylation,an important post-translational modification,regulates biosynthetic and metabolic pathways.This study aimed to identify critical acetylated proteins and specific modification sites involved in milk production and component synthesis in dairy goats,thereby elucidating the molecular mechanisms of lactation.We performed a comparative TMT-based acetylomic and proteomic analysis of mammary tissues from Saanen dairy goats during peak lactation and the dry period using LC–MS/MS.A candidate acetylation site was further investigated in goat mammary epithelial cells(GMECs)through site-directed mutagenesis and lipid metabolic assays,establishing functional links between acetylation and mammary lipid metabolism and providing a foundation for molecular strategies to improve milk quality and yield.Results We established a comprehensive mammary acetylome,identifying 862 significantly acetylated proteins and 2,028 modification sites across the two physiological phases.Differentially acetylated proteins were predominantly localized to the cytoplasm(39.98%).From these,54 key acetylated proteins,including MTOR,BCAT2,QARS1,GOT1,GOT2,BDH1,ACSS1,STAT5B,FABP5,and GPAM were prioritized as candidates involved in milk protein synthesis,milk fat synthesis,lactose synthesis,and other lactation-related processes.Among them,β-hydroxybutyrate dehydrogenase 1(BDH1)acetylation was characterized in detail.Members of the HDAC family were identified as primary regulators mediating BDH1 deacetylation.BDH1 acetylation promoted lipid droplet formation and triglyceride synthesis in GMECs.At the transcriptional level,BDH1 acetylation upregulated LXRα,ACSL1 and SCD1,whereas deacetylation downregulated SCD1,FASN,and ACSL1.Notably,BDH1 acetylation/deacetylation significantly reduced SREBP1 expression,linking this modification to coordinated control of lipogenic gene networks.Conclusions This study established,for the first time,the comprehensive acetylome of mammary gland tissues in dairy goats,revealing a substantial number of differentially acetylated proteins and modification sites.We demonstrate that acetylation of BDH1 regulated by HDACs promotes lipid droplet biogenesis and triglyceride synthesis in GMECs through transcriptional modulation of key lipogenic genes and suppression of SREBP1.These findings provide mechanistic insights into the post-translational regulation of mammary lipid metabolism and offer molecular targets for future genetic and nutritional strategies aimed at enhancing milk quality and yield in dairy goats.
基金supported by the Yanzhao Gold Talent Project of Hebei Province(NO.HJZD202506)。
文摘Objective Previous studies link lower body mass index(BMI)with increased obsessive-compulsive disorder(OCD)risk,yet other body mass indicators may be more etioloically relevant.We dissected the causal association between body fat mass(FM)and OCD.Methods Summary statistics from genome-wide association studies of European ancestry were utilized to conduct two-sample Mendelian randomization analysis.Heterogeneity,horizontal pleiotropy,and sensitivity analyses were performed to assess the robustness.Results The inverse variance weighting method demonstrated that a genetically predicted decrease in FM was causally associated with an increased OCD risk[odds ratio(OR)=0.680,95%confidence interval(CI):0.528–0.875,P=0.003].Similar estimates were obtained using the weighted median approach(OR=0.633,95%CI:0.438–0.915,P=0.015).Each standard deviation increases in genetically predicted body fat percentage corresponded to a reduced OCD risk(OR=0.638,95%CI:0.455–0.896,P=0.009).The sensitivity analysis confirmed the robustness of these findings with no outlier instrument variables identified.Conclusion The negative causal association between FM and the risk of OCD suggests that the prevention or treatment of mental disorders should include not only the control of BMI but also fat distribution and body composition.
文摘Overweight and obesity has been a major public health problem globally.It was estimated that more than 2.1 billion adults were affected by overweight or obese in 2021 worldwide,about one fifth of whom lived in China^([1]).By 2050,the country is forecast to remain the one with the largest population of overweight and obese globally^([1]),if no effective strategies were applied on overweight/obesity control.
基金supported by the National Natural Science Foundation of China(32325024,32400981,32222024,32271224,32471228,and 82270891)the National Key Research and Development Program of China(2023YFA1800400)+3 种基金the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(23SG22)the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0507300)the ECNU public platform for Innovation(011)the instruments sharing platform of School of Life Sciences.
文摘Type 1 diabetes(T1D)is defined by autoimmune-mediated destruction of the insulin-producing pancreatic β-cells.Impaired insulin secretion due to β-cell apoptosis and islet massloss is the main feature of T1D[1].Current therapeutic strategies for T1D are mainly through subcutaneous administration of insulin or islet/pancreas transplantation.
基金supported by grants from the Major Projects of Health Science Research Foundation for Middle-Aged and Young Scientist of Fujian Province,China,No.2022ZQNZD01010010the National Natural Science Foundation of China,No.82371390Fujian Province Scientific Foundation,No.2023J01725(all to XC).
文摘The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiquitous in the immune response of the central nervous system.The fat mass and obesity-related protein catalyzes the demethylation of N^(6)-methyladenosine modifications on mRNA and is widely expressed in various tissues,participating in the regulation of multiple diseases’biological processes.However,the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear.In this study,we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model.After fat mass and obesity interference,BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b^(+)/CD86^(+)cells and the secretion of pro-inflammatory cytokines.Fat mass and obesity-mediated N^(6)-methyladenosine demethylation accelerated the degradation of ADAM17 mRNA,while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA.Therefore,down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia.These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N^(6)-methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.
基金Supported by National Natural Science Foundation of China,No.82170651and the Research Support Fund of Hubei Microcirculation Society,No.HBWXH2024(1)-1.
文摘Intrapancreatic fat deposition(IPFD)has garnered increasing attention in recent years.The prevalence of IPFD is relatively high and associated with factors such as obesity,age,and sex.However,the pathophysiological mechanisms underlying IPFD remain unclear,with several potential contributing factors,including oxida-tive stress,alterations in the gut microbiota,and hormonal imbalances.IPFD was found to be highly correlated with the occurrence and prognosis of exocrine pan-creatic diseases.Although imaging techniques remain the primary diagnostic approach for IPFD,an expanding array of biomarkers and clinical scoring systems have been identified for screening purposes.Currently,effective treatments for IPFD are not available;however,existing medications,such as glucagon-like peptide-1 receptor agonists,and new therapeutic approaches explored in animal models have shown considerable potential for managing this disease.This paper reviews the pathogenesis of IPFD,its association with exocrine pancreatic disea-ses,and recent advancements in its diagnosis and treatment,emphasizing the significant clinical relevance of IPFD.
基金funded by the National Natural Science Foundation of China(32172761)the Key Research and Development Program of Hunan Province,China(2023NK2018)+1 种基金“Huxiang Young Talents Plan”Project of Hunan Province,China(2022RC1157)the College of Animal Science and Technology,Hunan Agricultural University for support。
文摘Intramuscular fat(IMF)is an important economic trait for pork quality,affecting meat flavour,juiciness,and tenderness.Hence,the improvement of IMF content is one of the hotspots of animal science to provide better meat product.Here,we found that most IMF-related genes are enriched in lipid metabolism processes,including fatty acid transport and uptake,fatty acid beta oxidation,lipid synthesis,lipid storage,and lipolysis.PPAR and AMPK signalling pathways are identified to be responsible for IMF deposition.Genetics and nongenetic factors(i.e.,diets,gut microbiota,age,sex and management)also positively or negatively regulate the IMF content in pigs.Taken together,this review deepens our understanding of how these factors affect pig IMF deposition and provides valuable information for moderately increasing IMF content.
基金Supported by the Leap-forward Development Program for Beijing Biopharmaceutical Industry(G20),No.Z171100001717008the Fundamental Research Funds for the Central Universities and Research projects on biomedical transformation of China-Japan Friendship Hospital,No.PYBZ1815.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disea-se.The accuracy of noninvasive biomarkers for detecting hepatic steatosis is still limited.AIM To assess the diagnostic performance of noninvasive steatosis biomarkers in diag-nosing NAFLD using magnetic resonance imaging proton density fat fraction(MRI-PDFF)as the gold standard.METHODS A total of 131 suspected NAFLD patients(60%male,median age 36 years)under-going MRI-PDFF were consecutively recruited from a tertiary hospital.Steatosis grades determined by MRI-PDFF were classified as none(<5%),mild(5%-11%),moderate(11%-17%),and severe(≥17%).Six steatosis biomarkers were calculated according to clinical parameters and laboratory tests,including fatty liver index,hepatic steatosis index,ZJU index,Framingham steatosis index,triglycerides and glucose index,and visceral adiposity index.The accuracy of these biomarkers in detecting hepatic steatosis was evaluated using the area under the receiver operating characteristic curves(AUCs).The Youden index was used to determine the optimal cut-off for each biomarker.The linear trend analysis of each biomarker across the steatosis grades was conducted by Mantel-Haenszelχ2 test.Spearman's rank correlation assessed the relationship between steatosis biomarkers and MRI-PDFF.RESULTS Steatosis grades based on MRI-PDFF prevalence were:None 27%,mild 40%,moderate 15%and severe 18%.Six steatosis biomarkers showed a linear trend across the steatosis grades and a significant positive correlation with MRI-PDFF.The six steatosis biomarkers demonstrated AUCs near 0.90(range:0.857-0.912,all P<0.001)for diagnosing NAFLD by MRI-PDFF≥5%.The optimal cut-offs showed sensitivity between 84.4%-91.7%and specificity between 71.4%-85.7%.The diagnostic performance of these biomarkers in detecting moderate-to-severe and severe steatosis was relatively weaker.CONCLUSION These noninvasive steatosis biomarkers accurately diagnosed NAFLD and correlated well with MRI-PDFF for detecting NAFLD,but they did not effectively detect moderate or severe steatosis.
基金Supported by the Postdoctoral Scholarship Grant,No.5552/2024 PROPG/PROPE N°06/2024.
文摘In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract,influenced by genetic predisposition,gut microbiota dysbiosis,and environmental factors.Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD.Further,visceral adipose tissue,particularly creeping fat,a mesenteric adipose tissue characterized by hypertrophy and fibrosis,has been implicated in CD pathogenesis,inflammation,and fibrosis.The bacteria from the gut microbiota may translocate into mesenteric adipose tissue,contributing to the formation of creeping fat and influencing CD progression.Although creeping fat may be a protective barrier against bacterial invasion,its expansion can damage adjacent tissues,leading to complications.Modulating gut microbiota through interventions such as fecal microbiota transplantation,probiotics,and prebiotics has shown potential in managing CD.However,more research is needed to clarify the mechanisms linking gut dysbiosis,creeping fat,and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.
基金supported by the Biological Breeding-Major Projects in National Science and Technology[grant numbers 2023ZD04044]the Natural Science Foundation of China Program[grant numbers 32072714].
文摘Background Intramuscular fat is an important factor in evaluating pork quality and varies widely among different pig breeds.However,the regulatory mechanism of circular RNAs(circRNAs)in lipid metabolism remains largely unexplored.Results We combined circRNA-seq and Ribo-seq data to screen a total of 18 circRNA candidates with coding potential,and circANKRD17 was found to be significantly elevated in the longissimus dorsi muscle of Lantang piglets,with a length of 1,844 nucleotides.Using single-cell sequencing,we identified 477 differentially expressed genes in IMF cells between Lantang and Landrace piglets,with enrichment in the PPAR signaling pathway.These genes included FABP4,FABP5,CPT1A,and UBC,consistent with the high levels of acylcarnitines observed in the longissimus dorsi muscles of the Lantang breed,as determined by lipidomic analysis.Further in vitro and in vivo experiments indicated that circANKRD17 can regulate lipid metabolism through various mechanisms involving the PPAR pathway,including promoting adipocyte differentiation,fatty acid transport and metabolism,triglyceride synthesis,and lipid droplet formation and maturation.In addition,we discovered that circANKRD17 has an open reading frame and can be translated into a novel 571-amino-acid protein that promotes lipid metabolism.Conclusions Our research provides new insights into the role of protein-coding circANKRD17,especially concerning the metabolic characteristics of pig breeds with higher intramuscular fat content.
基金Supported by Guangdong Provincial Clinical Research Center for Orthopedic Diseases,No.2023B110001the Excellent Medical Innovation Talent Program of the Eighth Affiliated Hospital of Sun Yat-sen University,No.YXYXCXRC202101+3 种基金the National Natural Science Foundation of China,No.82172349,No.82372372,No.22105229,No.32170708,No.82102530,No.82102541,No.82103098,No.82103909,No.82104182,No.82104350,No.82170427,No.82171291,No.82172215,No.82172385,and No.82302661Guangdong Natural Science Foundation,No.2023A1515010568 and No.2021A1515111057Shenzhen Science and Technology Program,No.JCYJ20220530144201004 and No.RCBS20210609104445097Futian Healthcare Research Project,No.FTWS2022022,No.FTWS2021013,No.FTWS2023072,and No.FTWS2022047.
文摘BACKGROUND Ankylosing spondylitis(AS)is recognized as a long-term inflammatory disorder that leads to inflammation in the spine and joints,alongside abnormal bone growth.In previous studies,we reported that mesenchymal stem cells(MSCs)derived from individuals with AS demonstrated a remarkable inhibition in the formation of osteoclasts compared to those obtained from healthy donors.The mechanism through which MSCs from AS patients achieve this inhibition remains unclear.AIM To investigate the potential underlying mechanism by which MSCs from individuals with ankylosing spondylitis(AS-MSCs)inhibit osteoclastogenesis.METHODS We analysed fat mass and obesity-associated(FTO)protein levels in AS-MSCs and MSCs from healthy donors and investigated the effects and mechanism by which FTO in MSCs inhibits osteoclastogenesis by coculturing and measuring the levels of tartrate-resistant acid phosphatase,nuclear factor of activated T cells 1 and cathepsin K.RESULTS We found that FTO,an enzyme responsible for removing methyl groups from RNA,was more abundantly expressed in MSCs from AS patients than in those from healthy donors.Reducing FTO levels was shown to diminish the capacity of MSCs to inhibit osteoclast development.Further experimental results revealed that FTO affects the stability of the long non-coding RNA activated by DNA damage(NORAD)by altering its N6-methyladenosine methylation status.Deactivating NORAD in MSCs significantly increased osteoclast formation by affecting miR-4284,which could regulate the MSC-mediated inhibition of osteoclastogenesis reported in our previous research.CONCLUSION This study revealed elevated FTO levels in AS-MSCs and found that FTO regulated the ability of AS-MSCs to inhibit osteoclast formation through the long noncoding RNA NORAD/miR-4284 axis.
