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
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
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
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
BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essenti...BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essential to explore novel therapeutic strategies.Curcumol,a sesquiterpenoid derived from traditional Chinese medicine,has shown anti-inflammatory and anti-cancer properties,but its potential role in DR remains unclear.AIM To investigate the therapeutic effects of curcumol on the progression of DR and to elucidate the underlying molecular mechanisms,particularly its impact on the fat mass and obesity-associated(FTO)protein and the long non-coding RNA(lncRNA)MAF transcription factor G antisense RNA 1(MAFG-AS1).METHODS A streptozotocin-induced mouse model of DR was established,followed by treatment with curcumol.Retinal damage and inflammation were evaluated through histological analysis and molecular assays.Human retinal vascular endothelial cells were exposed to high glucose conditions to simulate diabetic environments in vitro.Cell proliferation,migration,and inflammation markers were assessed in curcumoltreated cells.LncRNA microarray analysis identified key molecules regulated by curcumol,and further experiments were conducted to confirm the involvement of FTO and MAFG-AS1 in the progression of DR.RESULTS Curcumol treatment significantly reduced blood glucose levels and alleviated retinal damage in streptozotocininduced DR mouse models.In high-glucose-treated human retinal vascular endothelial cells,curcumol inhibited cell proliferation,migration,and inflammatory responses.LncRNA microarray analysis identified MAFG-AS1 as the most upregulated lncRNA following curcumol treatment.Mechanistically,FTO demethylated MAFG-AS1,stabilizing its expression.Rescue experiments demonstrated that the protective effects of curcumol against DR were mediated through the FTO/MAFG-AS1 signaling pathway.CONCLUSION Curcumol ameliorates the progression of DR by modulating the FTO/MAFG-AS1 axis,providing a novel therapeutic pathway for the treatment of DR.These findings suggest that curcumol-based therapies could offer a promising alternative for managing this debilitating complication of diabetes.展开更多
To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic an...To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors （P 〈 0.001） with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA （cross-section area）, W （sub-periosteal diameter）, Z （section modulus） and CT （cortical thickness） except between TBFM and BR （buckling ratio）. The peak bivariate LOD scores were 3.23 （20q12）, 2.47 （20p11）, 3.19 （6q27）, 1.68 （20p12）, and 2.47 （7q11） for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM ＆ Z in the female sub-population, and 6q27 and 17q11 had coincident link- ages for TBFM ＆ CSA and TBFM ＆ Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.展开更多
Breast cancer is one of the most commonly diagnosed cancers and one of the most significant sources of cancer mortality. Triple negative breast cancer (TNBC) is a particularly aggressive subtype that has proven diffic...Breast cancer is one of the most commonly diagnosed cancers and one of the most significant sources of cancer mortality. Triple negative breast cancer (TNBC) is a particularly aggressive subtype that has proven difficult to treat with standard chemotherapies. Obesity has also been shown to exacerbate breast cancer, and diagnoses of these two diseases frequently overlap. Both conditions are regulated in part by the fat mass and obesity-associated (FTO) demethylase, an RNA demethylase which may drive breast cancers through epigenetic alterations to gene expression. Methods of inhibiting FTO have been researched in vitro and in vivo as an alternative or adjunct to chemotherapies in multiple cancers, including breast cancer. Translating knowledge of the role of FTO in breast cancer and the development of novel agents may allow for improvements in the treatment of this refractory cancer. This review therefore aims to provide an overview of existing and developing chemical inhibitors of FTO that could be innovatively studied for the treatment of TNBC and associated comorbidity.展开更多
Background Non-alcoholic fatty liver disease （NAFLD） is a complex disorder and has been closely linked to obesity.The fat mass and obesity-associated （FTO） gene is a newly discovered gene related to obesity,which ...Background Non-alcoholic fatty liver disease （NAFLD） is a complex disorder and has been closely linked to obesity.The fat mass and obesity-associated （FTO） gene is a newly discovered gene related to obesity,which enhances oxidative stress and tipogenesis in NAFLD.The forkhead transcription factor O1 （FoxO1） is another important gene involved in NAFLD,which causes lipid disorders when insulin resistance appears in the liver.However,the interactions between FTO and FoxO1 during the pathogenesis of NAFLD have not been fully elucidated.This study was designed to identify the relationship between these two factors that are involved in the development of NAFLD.Methods This study includes two parts referred to as animal and cell experiments.Twelve female SPF C57BL/6 mice were fed a high-fat diet to serve as an NAFLD animal model.Aspartate aminotransferase （AST）,alanine aminotransferase （ALT）,total triglyceride （TG）,total cholesterol （TC）,alkaline phosphatase （ALP）,high-density lipoprotein （HDL）,and low-density lipoprotein （LDL） were measured.Immunohistochemical analysis was used to detect the expression and histological localization of FTO,FoxO1,and adenosine monophosphate （AMP）-activated protein kinase （AMPK）.The L02 cells were exposed to high fat for 24,48,or 72 hours.Oil red O staining was used to detect intracellular lipid droplets.Reverse transcription-polymerase chain reaction was used for analyzing the levels of FTO and FoxO1 mRNA.Results At the end of 10 weeks,ALP,ALT,AST,and LDL were significantly increased （P ＜0.01）,while TC and TG were also significantly higher （P ＜0.05）.In addition,HDL was significantly decreased （P ＜0.05）.The FTO and FoxO1 proteins were weakly expressed in the control group,but both FTO and FoxO1 were expressed significantly higher （P ＜0.01） in the experimental group,and the expression of the two factors was significantly correlated.AMPK in the high-fat group showed a low level of correlation with FTO,but not with FoxO1.Oil Red O staining results showed that the cells cultured in 50％ fetal bovine serum for 24,48,or 72 hours exhibited steatosis.FTO and FoxO1 mRNA were increased in the high-fat group compared with the normal group （P ＜0.01）.The expression levels of FTO and FoxO1 mRNA were the highest at 48 hours （P ＜0.05）.Conclusions A high-fat diet leads to higher expression of FTO,phosphorylation of FoxO1,and decreased phosphorylation of AMPK.These results suggest that the interactions between FTO and FoxO1 are closely related to the pathogenesis of NAFLD.展开更多
BACKGROUND: It is well established that the human aging process is associated with a significant decline in neuromuscular function and performance. Twin studies demonstrate that genetic factors partially explain the i...BACKGROUND: It is well established that the human aging process is associated with a significant decline in neuromuscular function and performance. Twin studies demonstrate that genetic factors partially explain the inter-individual variation of fat-free mass (FFM) and muscle strength. PURPOSE: To examine the association between the polymorphism of the gene IGF-2 with phenotypes strength and muscle mass of elderly women pre and post resistance training. METHODS: 76 elderly women participated in this analysis. These volunteers, who should be sedentary for at least 6 months before the study, were assigned four groups in relation to allele GAGG, AA, GAAA and GG. The first analysis compared 60 elderly women with GG and GA allele (GAGG) versus 16 elderly women with AA allele. The second analysis compared 54 elderly women with GA and AA (GAAA) versus 22 elderly women GG allele. The Body mass index, fat free mass, fat mass and Isokinetic Muscle Peak Torque were measured. All volunteers were participating in the Resistance Training program. The DNA was extracted from peripheral venous blood leukocytes using a salting out protocol. The primer for IGF-II gene exon 9 was 5’-GTCCCTGAACCAGCAAAGAG-3’ 0.5 μM (0.625 μl) Primer R-5’-TGATGGAAAAGGGAGTGAGG-3’ 0.5 μM (0.625 μl), Taq DNA Polimerase enzime 0.5 U (0.1 μl), água milli-Q (3.8 μl) 5 hg de DNA (3 μl). PCR amplification was performed in a programmable thermal cycler GeneAmp? PCR System 9700. RESULTS: The results of the first analysis GAGG × AA versus the group AA showed the relative increase in knee extensor peak torque relative and also in the fat-free mass and showed a decrease in the fat mass percentage in the GAGG group. The second analysis considered the group GAAA versus group GG showed decreases in the fat-free mass percentage in the GAAA group, also showed the relative increase in the fat-free mass in the GG group and decrease in the fat mass percentage in the GG group. CONCLUSIONS: The results of this study show that 24 weeks of the resistance training improved strength and muscle mass and decreased the fat mass. The results confirm this assertion and suggest the G allele presents more influence over the A allele, in relation to phenotypes strength and muscle mass in elderly women after resistance training.展开更多
An intramuscular injection (IMI) is an injection given directly into the central area of a specific muscle. Certain medicines need to be administered by the gluteal route for these to be effective. The aim of this stu...An intramuscular injection (IMI) is an injection given directly into the central area of a specific muscle. Certain medicines need to be administered by the gluteal route for these to be effective. The aim of this study was to determine the influence of body mass index (BMI), subcutaneous fat, and muscular thickness of the dorsogluteal IMI site among healthy Japanese women. There were 39 healthy female subjects who volunteered and met the criteria. Their ages ranged from 40s to 60s (50.82 ± 6.04). With the data collected using the B-mode ultrasound images of the dorsogluteal site, it was found that the distance from the epidermis to the under-fascia (DEUF) of the gluteus maximus was dissimilar between the subject’s right and left buttocks. It was found that the distance from the epidermis to the iliac bone (DEI) was significantly more on the right than on the left buttocks. In the case of an adult Japanese woman with a BMI of 21 or more, the DEUF of the gluteus medius was found to be about 30 mm, and the DEI was approximately 50 mm or more. Based on these findings, it is recommended that a needle length of 38 mm (1.5 inches) can be safely used to administer IMIs to the gluteus medius muscle to effectively and efficiently deliver medications through the IMI route.展开更多
Objective To assess the obesity prevalence in body mass index （BMI） and body fat percentage Saudi adults according to the international standards of （BF%）. Methods Five hundred and thirty healthy Saudi adults aged...Objective To assess the obesity prevalence in body mass index （BMI） and body fat percentage Saudi adults according to the international standards of （BF%）. Methods Five hundred and thirty healthy Saudi adults aged 18-72 years （mean 36.91＋15.22 years） were enrolled in this study. Their body composition was assessed by bioelectrical impendence analysis with a commercially available body composition analyzer. Standard BMI and BF% values were used to define obesity. Results The prevalence of underweight, normal underweight, overweight and obesity in Saudi adults according to the BMI criteria （〈18.5 kg/mz, 18.5-24.4 kg/m2, 25-29.9 kg/m2, 30 k＆/m2 and above, respectively） was 2.5%, 30.2%, 33.6%, and 33.8%, respectively, whereas the obesity prevalence was 60% （n=31g） in Saudi adults according to the BF% criteria （25% for males and 30% for females）, which was significantly higher than that according to BMI criteria. However, it was 50.6% （n=268） when the BMI cutoff point was 27.5 kg/m2, proposed by WHO for the Asian population. Kappa analysis showed that the obesity prevalence defined by BMI and BF% was higher in females than in males （k=0.530 vs k=0.418, P〈O.O001）. The sensitivity and specificity of BMI （30 kg/m2 and 27.5 kg/m2） were 54.1% and 96.7% and 76.4% and 88.2%, respectively, for obesity. A lower BMI cutoff point （26.60 kg/m2） was proposed in this study, which gave the maximum sensitivity （84.3%） and specificity （85.4%）, with a moderate kappa agreement （k=0.686）. Moreover, the obesity prevalence at this cutoff point （56.4%） was significantly higher than that recommended by WHO. Conclusion The specificity of BMI for obesity is high and its sensitivity is low in both sexes. Its sensitivity can be increased by changing BMI cutoff to a lower value. The choice of BF% reference is of great influence for the assessment of obesity prevalence according to the BMI.展开更多
Background: The lifestyle modification remains the fundamental approach for the obesity treatment. The aim of this study is to demonstrate the effect of the multimodal lifestyle intervention on the estimated visceral ...Background: The lifestyle modification remains the fundamental approach for the obesity treatment. The aim of this study is to demonstrate the effect of the multimodal lifestyle intervention on the estimated visceral fat area versus changes in musculoskeletal mass in a cohort of adult men with obesity. Subjects and Methods: A retrospective cohort study in which the file of eighty-two male subjects, aged 20 - 60 years, was studied for three months. Patients had been instructed to follow a balanced-hypocaloric diet, physical activity plan and general advice for combating the unhealthy lifestyle habits through the study period. Those who succeeded to loss > 5% of their body weight were classified as weight loser (WL) group, while others as weight resistant (WR) group. The results of In Body-720 bioelectric impedance analysis were used to report the fat mass (FM), visceral fat area (VFA), skeletal muscle mass (SMM), SMM/VFA ratio, osseous mass (OM), and basal metabolic rate (BMR) before and after the study period. Anthropometric measures, glucose, and lipid profile were also analyzed. Paired t-test was used to detect the significance of change between before and after measures, independent sample t-test was used to compare WL vs. WR groups. Results: There were significant decreases in weight, FM (p 0.05) and VFA (p 0.001), in addition to a significant rise of SMM/VFA ratio (p 0.05), together with insignificant changes of osseous mass, SMM and BMR after 3 months. Additionally, total cholesterol, low-density lipoprotein, and triglycerides were significantly reduced (P 0.05). The percentages of reduction in weight, FM and VFA in WL vs. WR groups were highly significant (p 0.001), while the percentages of change in SMM, SMM/VFA ratio and BMR were significant (p 0.05). Conclusion: Lifestyle modification might be effective in production of positive changes in the body composition of patients with obesity. These changes were more significant in weight losers.展开更多
Background: Obesity is a risk factor for cardiovascular disease and mortality. Significant weight loss has beneficial effects on left ventricular structure, in particular on regression of left ventricular hypertrophy ...Background: Obesity is a risk factor for cardiovascular disease and mortality. Significant weight loss has beneficial effects on left ventricular structure, in particular on regression of left ventricular hypertrophy (LVH). We therefore evaluated the consequences of significant weight loss on left ventricular morphology, hemodynamics and pericardial fat. Methods: We performed volumetric cardiac magnetic resonance (CMR) imaging before and after significant weight loss due to laparoscopic adjustable gastric banding (LAGB). CMR was used to measure cardiac mass, volume and function, as well as to quantify pericardial fat. Results: Eleven patients (age 40.5 ± 10 yrs, body mass index 42.5 ± 3.9 kg/m2) underwent CMR imaging before and a median 15.4 months after gastric banding. The BMI declined by 9.3 ± 3.3 kg/m2 (p Discussion: Significant weight loss in obesity is accompanied by a marked regression of LVH, with no apparent change in cardiac volume or function. The local effect of a diminished amount of pericardiac fat tissue may be more important than absolute weight loss with respect to the regression of LVH in obesity.展开更多
Body Mass Index (BMI) and Percentage Body Fat (%BF) values have been determined in cancer patients. In the study, 83 adult cancer patients were assessed of which 15 (18.1%) were males and 68 (81.9%) females. Body weig...Body Mass Index (BMI) and Percentage Body Fat (%BF) values have been determined in cancer patients. In the study, 83 adult cancer patients were assessed of which 15 (18.1%) were males and 68 (81.9%) females. Body weight and height of individual patients were used in calculating their respective BMI values. The respective %BF values were determined taking into consideration of the age, gender and BMI. Maximum values of BMI (34.71 kg/m2) and %BF (46.37%) were obtained, for which they were females and the minimum values of BMI (12.08 kg/m2) and %BF (12.35%) respectively. The patient with the minimum %BF value was male and that of BMI was female. It was observed from the results that females have higher values of both BMI and %BF than their male counterparts. The study reveals higher rate of female cancer incidence than males.展开更多
Obesity is included in the definition of metabolic syndrome. However, there are many controversies surrounding the evaluation of obesity such as body mass index (BMI) and waist circumference (WC) in the definition of ...Obesity is included in the definition of metabolic syndrome. However, there are many controversies surrounding the evaluation of obesity such as body mass index (BMI) and waist circumference (WC) in the definition of metabolic syndrome among various populations. To understand precisely how various anthropometric indices of obesity influence metabolic parameters, we studied the correlations of BMI, WC (Japanese criteria), WC (IDF criteria), visceral fat area (VFA), subcutaneous fat area (SFA) and the VFA/SFA ratio with metabolic parameters in patients with type 2 diabetes. The influences of BMI and WC on diastolic blood pressure and HDL-cholesterol were larger than VFA, whereas the influences of visceral fat area on triglyceride, very low-density lipoprotein-cholesterol, C-peptide and high-sensitivity C-reactive protein were larger than BMI and WC. WC (IDF) was the strongest determinant of adiponectin among anthropometric indices. Present study showed significant different associations of BMI, Japan- and IDF-defined WC, VFA, SFA and the VFA/SFA ratio with blood pressure, glucose and lipid metabolism, and adipocytokines in Japanese patients with type 2 diabetes.展开更多
Purpose:This study was aimed to analyze the mediation role of cardiorespiratory fitness(CRF)on the association between fatness and cardiometabolic risk scores(CMRs)in European adolescents.Methods:A cross-sectional stu...Purpose:This study was aimed to analyze the mediation role of cardiorespiratory fitness(CRF)on the association between fatness and cardiometabolic risk scores(CMRs)in European adolescents.Methods:A cross-sectional study was conducted in adolescents(n=525;46%boys;14.1±1.1 years old,mean ±SD)from 10 European cities involved in the Healthy Lifestyle in Europe by Nutrition in Adolescence study.CRF was measured by means of the shuttle run test,while fatness measures included body mass index(BMI),waist to height ratio,and fat mass index estimated from skinfold thicknesses.A clustered CMRs was computed by summing the standardized values of homeostasis model assessment,systolic blood pressure,triglycerides,total cholesterol/highdensity lipoprotein cholesterol ratio,and leptin.Results:Linear regression models indicated that CRF acted as an important and partial mediator in the association between fatness and CMRs in 1217-year-old adolescents(for BMI:coefficients of the indirect role b=0.058(95%confidence interval(95%CI):0.023-0.101),Sobel test z=3.11(10.0%mediation);for waist to height ratio:b=4.279(95%CI:2.242-7.059),z=3.86(11.5%mediation);and for fat mass index:b=0.060(95%CI:0.020-0.106),z=2.85(9.4%mediation);all p<0.01).Conclusion:In adolescents,the association between fatness and CMRs could be partially decreased with improvements to fitness levels;therefore,CRF contribution both in the clinical field and public health could be important to consider and promote in adolescents independently of their fatness levels.展开更多
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 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 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.
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.
文摘BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essential to explore novel therapeutic strategies.Curcumol,a sesquiterpenoid derived from traditional Chinese medicine,has shown anti-inflammatory and anti-cancer properties,but its potential role in DR remains unclear.AIM To investigate the therapeutic effects of curcumol on the progression of DR and to elucidate the underlying molecular mechanisms,particularly its impact on the fat mass and obesity-associated(FTO)protein and the long non-coding RNA(lncRNA)MAF transcription factor G antisense RNA 1(MAFG-AS1).METHODS A streptozotocin-induced mouse model of DR was established,followed by treatment with curcumol.Retinal damage and inflammation were evaluated through histological analysis and molecular assays.Human retinal vascular endothelial cells were exposed to high glucose conditions to simulate diabetic environments in vitro.Cell proliferation,migration,and inflammation markers were assessed in curcumoltreated cells.LncRNA microarray analysis identified key molecules regulated by curcumol,and further experiments were conducted to confirm the involvement of FTO and MAFG-AS1 in the progression of DR.RESULTS Curcumol treatment significantly reduced blood glucose levels and alleviated retinal damage in streptozotocininduced DR mouse models.In high-glucose-treated human retinal vascular endothelial cells,curcumol inhibited cell proliferation,migration,and inflammatory responses.LncRNA microarray analysis identified MAFG-AS1 as the most upregulated lncRNA following curcumol treatment.Mechanistically,FTO demethylated MAFG-AS1,stabilizing its expression.Rescue experiments demonstrated that the protective effects of curcumol against DR were mediated through the FTO/MAFG-AS1 signaling pathway.CONCLUSION Curcumol ameliorates the progression of DR by modulating the FTO/MAFG-AS1 axis,providing a novel therapeutic pathway for the treatment of DR.These findings suggest that curcumol-based therapies could offer a promising alternative for managing this debilitating complication of diabetes.
基金supported by grants from NIH in USA (No. K01 AR02170-01, R01 AR45349-01, R01 GM60402-01 A1, R01 AG026564-01A2, and R21 AG027110-01A1)the Natural Science Foundation o China (NSFC) (No. 30600364)The genotyping experiment was performed by Marshfield Center for Medical Genetics and supported by NHLB Mammalian Genotyping Service (Contract No. HV48141)
文摘To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors （P 〈 0.001） with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA （cross-section area）, W （sub-periosteal diameter）, Z （section modulus） and CT （cortical thickness） except between TBFM and BR （buckling ratio）. The peak bivariate LOD scores were 3.23 （20q12）, 2.47 （20p11）, 3.19 （6q27）, 1.68 （20p12）, and 2.47 （7q11） for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM ＆ Z in the female sub-population, and 6q27 and 17q11 had coincident link- ages for TBFM ＆ CSA and TBFM ＆ Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.
文摘Breast cancer is one of the most commonly diagnosed cancers and one of the most significant sources of cancer mortality. Triple negative breast cancer (TNBC) is a particularly aggressive subtype that has proven difficult to treat with standard chemotherapies. Obesity has also been shown to exacerbate breast cancer, and diagnoses of these two diseases frequently overlap. Both conditions are regulated in part by the fat mass and obesity-associated (FTO) demethylase, an RNA demethylase which may drive breast cancers through epigenetic alterations to gene expression. Methods of inhibiting FTO have been researched in vitro and in vivo as an alternative or adjunct to chemotherapies in multiple cancers, including breast cancer. Translating knowledge of the role of FTO in breast cancer and the development of novel agents may allow for improvements in the treatment of this refractory cancer. This review therefore aims to provide an overview of existing and developing chemical inhibitors of FTO that could be innovatively studied for the treatment of TNBC and associated comorbidity.
文摘Background Non-alcoholic fatty liver disease （NAFLD） is a complex disorder and has been closely linked to obesity.The fat mass and obesity-associated （FTO） gene is a newly discovered gene related to obesity,which enhances oxidative stress and tipogenesis in NAFLD.The forkhead transcription factor O1 （FoxO1） is another important gene involved in NAFLD,which causes lipid disorders when insulin resistance appears in the liver.However,the interactions between FTO and FoxO1 during the pathogenesis of NAFLD have not been fully elucidated.This study was designed to identify the relationship between these two factors that are involved in the development of NAFLD.Methods This study includes two parts referred to as animal and cell experiments.Twelve female SPF C57BL/6 mice were fed a high-fat diet to serve as an NAFLD animal model.Aspartate aminotransferase （AST）,alanine aminotransferase （ALT）,total triglyceride （TG）,total cholesterol （TC）,alkaline phosphatase （ALP）,high-density lipoprotein （HDL）,and low-density lipoprotein （LDL） were measured.Immunohistochemical analysis was used to detect the expression and histological localization of FTO,FoxO1,and adenosine monophosphate （AMP）-activated protein kinase （AMPK）.The L02 cells were exposed to high fat for 24,48,or 72 hours.Oil red O staining was used to detect intracellular lipid droplets.Reverse transcription-polymerase chain reaction was used for analyzing the levels of FTO and FoxO1 mRNA.Results At the end of 10 weeks,ALP,ALT,AST,and LDL were significantly increased （P ＜0.01）,while TC and TG were also significantly higher （P ＜0.05）.In addition,HDL was significantly decreased （P ＜0.05）.The FTO and FoxO1 proteins were weakly expressed in the control group,but both FTO and FoxO1 were expressed significantly higher （P ＜0.01） in the experimental group,and the expression of the two factors was significantly correlated.AMPK in the high-fat group showed a low level of correlation with FTO,but not with FoxO1.Oil Red O staining results showed that the cells cultured in 50％ fetal bovine serum for 24,48,or 72 hours exhibited steatosis.FTO and FoxO1 mRNA were increased in the high-fat group compared with the normal group （P ＜0.01）.The expression levels of FTO and FoxO1 mRNA were the highest at 48 hours （P ＜0.05）.Conclusions A high-fat diet leads to higher expression of FTO,phosphorylation of FoxO1,and decreased phosphorylation of AMPK.These results suggest that the interactions between FTO and FoxO1 are closely related to the pathogenesis of NAFLD.
基金National Council for Scientific and Technological Development (CNPq)Catholic University
文摘BACKGROUND: It is well established that the human aging process is associated with a significant decline in neuromuscular function and performance. Twin studies demonstrate that genetic factors partially explain the inter-individual variation of fat-free mass (FFM) and muscle strength. PURPOSE: To examine the association between the polymorphism of the gene IGF-2 with phenotypes strength and muscle mass of elderly women pre and post resistance training. METHODS: 76 elderly women participated in this analysis. These volunteers, who should be sedentary for at least 6 months before the study, were assigned four groups in relation to allele GAGG, AA, GAAA and GG. The first analysis compared 60 elderly women with GG and GA allele (GAGG) versus 16 elderly women with AA allele. The second analysis compared 54 elderly women with GA and AA (GAAA) versus 22 elderly women GG allele. The Body mass index, fat free mass, fat mass and Isokinetic Muscle Peak Torque were measured. All volunteers were participating in the Resistance Training program. The DNA was extracted from peripheral venous blood leukocytes using a salting out protocol. The primer for IGF-II gene exon 9 was 5’-GTCCCTGAACCAGCAAAGAG-3’ 0.5 μM (0.625 μl) Primer R-5’-TGATGGAAAAGGGAGTGAGG-3’ 0.5 μM (0.625 μl), Taq DNA Polimerase enzime 0.5 U (0.1 μl), água milli-Q (3.8 μl) 5 hg de DNA (3 μl). PCR amplification was performed in a programmable thermal cycler GeneAmp? PCR System 9700. RESULTS: The results of the first analysis GAGG × AA versus the group AA showed the relative increase in knee extensor peak torque relative and also in the fat-free mass and showed a decrease in the fat mass percentage in the GAGG group. The second analysis considered the group GAAA versus group GG showed decreases in the fat-free mass percentage in the GAAA group, also showed the relative increase in the fat-free mass in the GG group and decrease in the fat mass percentage in the GG group. CONCLUSIONS: The results of this study show that 24 weeks of the resistance training improved strength and muscle mass and decreased the fat mass. The results confirm this assertion and suggest the G allele presents more influence over the A allele, in relation to phenotypes strength and muscle mass in elderly women after resistance training.
文摘An intramuscular injection (IMI) is an injection given directly into the central area of a specific muscle. Certain medicines need to be administered by the gluteal route for these to be effective. The aim of this study was to determine the influence of body mass index (BMI), subcutaneous fat, and muscular thickness of the dorsogluteal IMI site among healthy Japanese women. There were 39 healthy female subjects who volunteered and met the criteria. Their ages ranged from 40s to 60s (50.82 ± 6.04). With the data collected using the B-mode ultrasound images of the dorsogluteal site, it was found that the distance from the epidermis to the under-fascia (DEUF) of the gluteus maximus was dissimilar between the subject’s right and left buttocks. It was found that the distance from the epidermis to the iliac bone (DEI) was significantly more on the right than on the left buttocks. In the case of an adult Japanese woman with a BMI of 21 or more, the DEUF of the gluteus medius was found to be about 30 mm, and the DEI was approximately 50 mm or more. Based on these findings, it is recommended that a needle length of 38 mm (1.5 inches) can be safely used to administer IMIs to the gluteus medius muscle to effectively and efficiently deliver medications through the IMI route.
文摘Objective To assess the obesity prevalence in body mass index （BMI） and body fat percentage Saudi adults according to the international standards of （BF%）. Methods Five hundred and thirty healthy Saudi adults aged 18-72 years （mean 36.91＋15.22 years） were enrolled in this study. Their body composition was assessed by bioelectrical impendence analysis with a commercially available body composition analyzer. Standard BMI and BF% values were used to define obesity. Results The prevalence of underweight, normal underweight, overweight and obesity in Saudi adults according to the BMI criteria （〈18.5 kg/mz, 18.5-24.4 kg/m2, 25-29.9 kg/m2, 30 k＆/m2 and above, respectively） was 2.5%, 30.2%, 33.6%, and 33.8%, respectively, whereas the obesity prevalence was 60% （n=31g） in Saudi adults according to the BF% criteria （25% for males and 30% for females）, which was significantly higher than that according to BMI criteria. However, it was 50.6% （n=268） when the BMI cutoff point was 27.5 kg/m2, proposed by WHO for the Asian population. Kappa analysis showed that the obesity prevalence defined by BMI and BF% was higher in females than in males （k=0.530 vs k=0.418, P〈O.O001）. The sensitivity and specificity of BMI （30 kg/m2 and 27.5 kg/m2） were 54.1% and 96.7% and 76.4% and 88.2%, respectively, for obesity. A lower BMI cutoff point （26.60 kg/m2） was proposed in this study, which gave the maximum sensitivity （84.3%） and specificity （85.4%）, with a moderate kappa agreement （k=0.686）. Moreover, the obesity prevalence at this cutoff point （56.4%） was significantly higher than that recommended by WHO. Conclusion The specificity of BMI for obesity is high and its sensitivity is low in both sexes. Its sensitivity can be increased by changing BMI cutoff to a lower value. The choice of BF% reference is of great influence for the assessment of obesity prevalence according to the BMI.
文摘Background: The lifestyle modification remains the fundamental approach for the obesity treatment. The aim of this study is to demonstrate the effect of the multimodal lifestyle intervention on the estimated visceral fat area versus changes in musculoskeletal mass in a cohort of adult men with obesity. Subjects and Methods: A retrospective cohort study in which the file of eighty-two male subjects, aged 20 - 60 years, was studied for three months. Patients had been instructed to follow a balanced-hypocaloric diet, physical activity plan and general advice for combating the unhealthy lifestyle habits through the study period. Those who succeeded to loss > 5% of their body weight were classified as weight loser (WL) group, while others as weight resistant (WR) group. The results of In Body-720 bioelectric impedance analysis were used to report the fat mass (FM), visceral fat area (VFA), skeletal muscle mass (SMM), SMM/VFA ratio, osseous mass (OM), and basal metabolic rate (BMR) before and after the study period. Anthropometric measures, glucose, and lipid profile were also analyzed. Paired t-test was used to detect the significance of change between before and after measures, independent sample t-test was used to compare WL vs. WR groups. Results: There were significant decreases in weight, FM (p 0.05) and VFA (p 0.001), in addition to a significant rise of SMM/VFA ratio (p 0.05), together with insignificant changes of osseous mass, SMM and BMR after 3 months. Additionally, total cholesterol, low-density lipoprotein, and triglycerides were significantly reduced (P 0.05). The percentages of reduction in weight, FM and VFA in WL vs. WR groups were highly significant (p 0.001), while the percentages of change in SMM, SMM/VFA ratio and BMR were significant (p 0.05). Conclusion: Lifestyle modification might be effective in production of positive changes in the body composition of patients with obesity. These changes were more significant in weight losers.
文摘Background: Obesity is a risk factor for cardiovascular disease and mortality. Significant weight loss has beneficial effects on left ventricular structure, in particular on regression of left ventricular hypertrophy (LVH). We therefore evaluated the consequences of significant weight loss on left ventricular morphology, hemodynamics and pericardial fat. Methods: We performed volumetric cardiac magnetic resonance (CMR) imaging before and after significant weight loss due to laparoscopic adjustable gastric banding (LAGB). CMR was used to measure cardiac mass, volume and function, as well as to quantify pericardial fat. Results: Eleven patients (age 40.5 ± 10 yrs, body mass index 42.5 ± 3.9 kg/m2) underwent CMR imaging before and a median 15.4 months after gastric banding. The BMI declined by 9.3 ± 3.3 kg/m2 (p Discussion: Significant weight loss in obesity is accompanied by a marked regression of LVH, with no apparent change in cardiac volume or function. The local effect of a diminished amount of pericardiac fat tissue may be more important than absolute weight loss with respect to the regression of LVH in obesity.
文摘Body Mass Index (BMI) and Percentage Body Fat (%BF) values have been determined in cancer patients. In the study, 83 adult cancer patients were assessed of which 15 (18.1%) were males and 68 (81.9%) females. Body weight and height of individual patients were used in calculating their respective BMI values. The respective %BF values were determined taking into consideration of the age, gender and BMI. Maximum values of BMI (34.71 kg/m2) and %BF (46.37%) were obtained, for which they were females and the minimum values of BMI (12.08 kg/m2) and %BF (12.35%) respectively. The patient with the minimum %BF value was male and that of BMI was female. It was observed from the results that females have higher values of both BMI and %BF than their male counterparts. The study reveals higher rate of female cancer incidence than males.
文摘Obesity is included in the definition of metabolic syndrome. However, there are many controversies surrounding the evaluation of obesity such as body mass index (BMI) and waist circumference (WC) in the definition of metabolic syndrome among various populations. To understand precisely how various anthropometric indices of obesity influence metabolic parameters, we studied the correlations of BMI, WC (Japanese criteria), WC (IDF criteria), visceral fat area (VFA), subcutaneous fat area (SFA) and the VFA/SFA ratio with metabolic parameters in patients with type 2 diabetes. The influences of BMI and WC on diastolic blood pressure and HDL-cholesterol were larger than VFA, whereas the influences of visceral fat area on triglyceride, very low-density lipoprotein-cholesterol, C-peptide and high-sensitivity C-reactive protein were larger than BMI and WC. WC (IDF) was the strongest determinant of adiponectin among anthropometric indices. Present study showed significant different associations of BMI, Japan- and IDF-defined WC, VFA, SFA and the VFA/SFA ratio with blood pressure, glucose and lipid metabolism, and adipocytokines in Japanese patients with type 2 diabetes.
文摘Purpose:This study was aimed to analyze the mediation role of cardiorespiratory fitness(CRF)on the association between fatness and cardiometabolic risk scores(CMRs)in European adolescents.Methods:A cross-sectional study was conducted in adolescents(n=525;46%boys;14.1±1.1 years old,mean ±SD)from 10 European cities involved in the Healthy Lifestyle in Europe by Nutrition in Adolescence study.CRF was measured by means of the shuttle run test,while fatness measures included body mass index(BMI),waist to height ratio,and fat mass index estimated from skinfold thicknesses.A clustered CMRs was computed by summing the standardized values of homeostasis model assessment,systolic blood pressure,triglycerides,total cholesterol/highdensity lipoprotein cholesterol ratio,and leptin.Results:Linear regression models indicated that CRF acted as an important and partial mediator in the association between fatness and CMRs in 1217-year-old adolescents(for BMI:coefficients of the indirect role b=0.058(95%confidence interval(95%CI):0.023-0.101),Sobel test z=3.11(10.0%mediation);for waist to height ratio:b=4.279(95%CI:2.242-7.059),z=3.86(11.5%mediation);and for fat mass index:b=0.060(95%CI:0.020-0.106),z=2.85(9.4%mediation);all p<0.01).Conclusion:In adolescents,the association between fatness and CMRs could be partially decreased with improvements to fitness levels;therefore,CRF contribution both in the clinical field and public health could be important to consider and promote in adolescents independently of their fatness levels.
