Intracellular Retention of Human Melanocortin-4 Receptor:A Molecular Mechanism Underlying Early-onset Obesity in F261S Pedigree of Chinese

Objective To investigate how F261S mutation identified from Chinese obese patients affects the function of melanocorfin 4 receptor (MC4R) and to analyze the obesity-related phenotypes in subjects carrying the F261S mutation. Methods F261S mutant of MC4R was generated by site-directed mutagenesis. Plasmids encoding wild-type or F261S mutant of MC4R were transfected into HEK293 and COS-7 cells to examine their functional characteristics. Signaling properties of F261S MC4R were assessed by measuring intracellular cAMP levels in response to α-MSH stimulation. Cell surface expression of F261S MC4R was compared with that of wild-type MC4R. Clinical examinations were performed in subjects carrying F261S mutation and in non-mutated controls. Results The a-MSH-stimulated reporter gene activity was significantly reduced in cells expressing F261S MC4R, with a maximal response equal to 57% of wild-type MC4R. The F261S mutation also led to a significant change in the EC50 value compared with the wild-type receptor (P〈0.01). Immunofluorescent assay revealed a marked reduction in plasma membrane localization of the MC4R in cells expressing the F261S mutant receptor. The resting metabolic rate and fat composition of the mutant carriers were not significantly different from those of the non-mutated obese controls. Conclusions The decreased response to α-MSH due to the intracellular retention of MC4R may cause early-onset obesity in the F261S pedigree of Chinese.

Microbial phenolic metabolites 3-(3',4'-dihydroxyphenyl)propanoic acid and 3',4'-dihydroxyphenylacetic acid prevent obesity in mice fed high-fat diet

Obesity is associated with numerous metabolic disorders,and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity.However,the effect of 3-(3’,4’-dihydroxyphenyl)propanoic acid(DHPA)and 3’,4’-dihydroxyphenylacetic acid(DHAA),two main metabolites of dietary polyphenols,on obesity remains poorly understood.In this study,DHPA and DHAA were found to alleviate obesity,as well as regulate insulin resistance,lipid metabolism,and oxidative stress response in high-fat diet(HFD)mice.Surprisingly,the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome,but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion,tyrosine metabolism,pentose phosphate and tricarboxylic acid(TCA)cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Correlation analysis revealed that the differential metabolites are strongly associated with body weight,blood glucose,insulin level,and superoxide dismutase(SOD)enzyme activity.Our results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose,lipid and tyrosine metabolism pathways.

Effect of bariatric surgery on metabolism in diabetes and obesity comorbidity:Insight from recent research

Obesity is a prevalent cause of diabetes mellitus(DM)and is a serious danger to human health.Type 2 DM(T2DM)mostly occurs along with obesity.Foodborne obesity-induced DM is caused by an excessive long-term diet and surplus energy.Bariatric surgery can improve the symptoms of T2DM in some obese patients.But different types of bariatric surgery may have different effects.There are some models built by researchers to discuss the surgical procedures’effects on me-tabolism in diabetes animal models and diabetes patients.It is high time to conclude all this effects and recommend procedures that can better improve metabolism.

Association between childhood obesity and gut microbiota:16S rRNA gene sequencing-based cohort study

BACKGROUND This study aimed to identify characteristic gut genera in obese and normal-weight children(8-12 years old)using 16S rDNA sequencing.The research aimed to provide insights for mechanistic studies and prevention strategies for childhood obesity.Thirty normal-weight and thirty age-and sex-matched obese children were included.Questionnaires and body measurements were collected,and fecal samples underwent 16S rDNA sequencing.Significant differences in body mass index(BMI)and body-fat percentage were observed between the groups.Analysis of gut microbiota diversity revealed lowerα-diversity in obese children.Differences in gut microbiota composition were found between the two groups.Prevotella and Firmicutes were more abundant in the obese group,while Bacteroides and Sanguibacteroides were more prevalent in the control group.AIM To identify the characteristic gut genera in obese and normal-weight children(8-12-year-old)using 16S rDNA sequencing,and provide a basis for subsequent mechanistic studies and prevention strategies for childhood obesity.METHODS Thirty each normal-weight,1:1 matched for age and sex,and obese children,with an obese status from 2020 to 2022,were included in the control and obese groups,respectively.Basic information was collected through questionnaires and body measurements were obtained from both obese and normal-weight children.Fecal samples were collected from both groups and subjected to 16S rDNA sequencing using an Illumina MiSeq sequencing platform for gut microbiota diversity analysis.RESULTS Significant differences in BMI and body-fat percentage were observed between the two groups.The Ace and Chao1 indices were significantly lower in the obese group than those in the control group,whereas differences were not significant in the Shannon and Simpson indices.Kruskal-Wallis tests indicated significant differences in unweighted and weighted UniFrac distances between the gut microbiota of normal-weight and obese children(P<0.01),suggesting substantial disparities in both the species and quantity of gut microbiota between the two groups.Prevotella,Firmicutes,Bacteroides,and Sanguibacteroides were more abundant in the obese and control groups,respectively.Heatmap results demonstrated significant differences in the gut microbiota composition between obese and normal-weight children.CONCLUSION Obese children exhibited lowerα-diversity in their gut microbiota than did the normal-weight children.Significant differences were observed in the composition of gut microbiota between obese and normal-weight children.

Combating obesity in Southeast Asia countries:current status and the way forward

Obesity is gaining prominence as a serious public health challenge in the Southeast Asia(SEA)region,with an alarming rate of increase in its prevalence.Countries in the region have shown commitment to curbing the rise of obesity by establishing policies,strategies,and action plans.This paper summarises the current situation and strategies undertaken to combat obesity and related chronic diseases.Although a range of policies and strate-gies have been developed,including national nutrition action plans,community intervention programmes,fiscal measures,nutrition labelling to promote healthier choices,countries in the region are struggling to make signifi-cant progress toward halting the scourge of obesity.It is imperative to strengthen existing health systems with a paradigm shift from a focus on"sick care"to and enhancing nutrition initiatives to support obesity prevention.A comprehensive and coordinated approach is essential,one that emphasises high-level coordination across all lev-els of government and multiple sectors,and a unified plan rather than fragmented initiatives.For strategies to be effective and sustainable,they must address the fundamental environmental determinants of poor dietary choices and nutritional inequalities.A more holistic approach is clearly needed to improve the entire food environment,which in SEA countries must include the multitude of eating places where large segments of the population"eat out"everyday to meet their energy and nutrient needs.There is a recognised need for more comprehensive measures to promote healthy eating among school children and ensure a supportive environment for lifelong healthy habits.This paper calls for a whole-of-government,whole-of-society approach that combines changes to the fundamental food environment and accompanied by systematic monitoring and surveillance systems to achieve long-lasting health outcomes.

The 10th China Obesity Science Conference Held in Beijing

The 10th China Obesity Science Conference was held in Beijing from May 10th to 11th, 2024. Experts from authoritative institutions such as the National Health Commission, the Chinese Center for Disease Control and Prevention, and the China Institute of Sports Science gathered to discuss on the topics including obesity prevalence trends.

Epidemiological Aspects of Obesity, Overweight and Cardiovascular Risk Factors at Associes in Semi-Urban Areas (Case of Sébikotane)

Introduction: Obesity and overweight are a public health problem. The general objective was to determine the epidemiological aspects of obesity, overweight and associated risk factors in a semi-urban environment. Patients and Methods: This was a cross-sectional, descriptive study conducted on November 28 and 29, 2023 in Sébikotane. It focused on volunteers for screening for chronic non-communicable diseases. Epidemiological and clinical data were evaluated. Results: One hundred and twenty-nine cases of obesity were recorded (28%). Two hundred and eighty-two cases were overweight or obese (61.3%). The mean age was 49.55 years, with a standard deviation of 12.41 years. The age group [40 - 49 years] was the most representative, with 85 cases (30.1%), and the majority were female, with 264 cases (93.6%). Primary education was the most common, with 75 cases (46.3%). Grade 1 obesity concerned ninety-seven cases (75.2%), and diabetes was present in thirty cases (23%). Hypertension was present in ninety-five cases (33.7%). Obesity was more marked in the age group [40 - 49 years] with 45 cases (36%). Conclusion: Obesity and overweight are a major cause of morbidity and mortality. The development and implementation of a prevention and management program is essential.

Time trends and disparities of obesity and related national policies and programs in Nepal:a systematic review

Objective Overweight and obesity prevalence has increased in low-income countries.This study systematically reviewed the obesity trend,disparities,and prevention and control efforts in Nepal.Methods We searched PubMed and Google Scholar for articles and reports published between January 1,2004 and December 31,2022.Additional information on National policies and programs related to obesity prevention was retrieved from governmental websites and consultation with relevant experts.Overweight and obesity were defined using the World Health Organization body mass index cut points.Thirty-two studies and reports were included.Results Overall,overweight and obesity rates increased in all groups in Nepal although nationally representative data remained limited.The combined overweight and obesity(OW/OB)and obesity rates in women aged 15-49 years increased from 8.5%to 22.2%and from 0.9%to 5.1%between 2006 and 2016,respectively.OW/OB and obesity rates in men were 17.1%and 2.5%based on data from the 2016 Demographic and Health Survey.OW/OB rate in under-five children increased from 0.6%to 2.8%between 2006 and 2016.Obesity rates for school-age(5-9 years)boys and girls in 2016 were 2.4%and 2.8%,respectively,and were 1.1%and 1.4%for male and female adolescents aged 10-19 years,respectively.OW/OB prevalence was much higher among women,residents in urban areas and central provinces,and in higher socioeconomic status groups.Projected prevalence of OW/OB and obesity for 2030 in adults aged 15-49 was 44.7%and 8.3%,respectively,while it was 2.2%for OW/OB in preschool children.Policies and direct interventions that specifically focused on obesity prevention and control are limited.Conclusions OW/OB prevalence in Nepal has increased during the past 1.8 decades,disproportionately affecting population groups.Existing interventions mostly focused on undernutrition with some indirect implications for obesity prevention.In the future,Nepal needs to develop population-based programs for obesity prevention.

New advances of adiponectin in regulating obesity and related metabolic syndromes

Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.

The Prevalence of Overweight/Obesity and Related Comorbidities among HIV-Positive and HIV-Negative Patients Attending the Same Clinics in Gaborone, Botswana

Context: Antiretroviral therapy (ART) helps restore the health status of people living with HIV (PLHIV). Likewise, it increases the risk of overweight/obesity and related comorbidities among the recipients. In countries like Botswana where ±84% of PLHIV is on ART, the paucity of data comparing overweight/obesity between HIV-positive on ART and HIV-negative patients may impede clinical and policy decision-making. This study sought to estimate and compare: i) the prevalence of overweight/obesity between HIV-positive on ART and HIV-negative patients;ii) the prevalence of hypertension (HTN), diabetes mellitus (DM)/coronary heart disease (CHD) between HIV-positive patients on ART and HIV-negative patients attending same outpatient departments of general clinics in Gaborone, Botswana. Patients and Methods: Five hundred eighty-one (581) outpatients were recruited in four major clinics of Gaborone, Botswana, between June and July 2019;294 or 51% of them were HIV-negative and 287 or 49% were HIV-positive on ART. The prevalence of overweight/obesity and of HTN and DM/CHD were calculated and examined using stratified analysis. Subgroups were compared using Chi-square analysis with Yates correction or Fisher exact test and t-student test for continuous data. Results: Major findings after stratification of the study population by HIV status were: i) the prevalence of all categories of (BMI), including overweight/obesity, were comparable between HIV-negative-patients and HIV-positive. In fact, there were 24 (8.0%) cases of underweight among HIV-negative-Patients and 15(5%) cases among HIV-positive patients, p = 0.2;145 (49%) HIV-negative-patients and 128 (45%) HIV-positive, p = 0.07 cases of normal weight;72 (25%) HIV-negative-patients and 87 (30%) HIV-positive, p = 0.08, were overweight;53 (18%) HIV-negative-patients and 57 (20%) HIV-positive, p = 0.12, were obese;125 (43%) HIV-negative patients and 144 (50%) HIV-positive, p=0.06 were overweight/obese;ii) the prevalence of HTN and DM/CHD among HIV-positive-patients were significantly lower (p < 0.05) compared to HIV-negative patients: There were 32 (10.9%) cases of HTN among HIV-negative patients compared to 18 (6.3%) cases of HTN among HIV-positive patients, p = 0.001;32 (11%) cases of DM/CHD HIV-negative patients compared to 4 (1.4%) cases of DM/CHD among HIV-positive patients, p = 0.001. Conclusion: the prevalence of overweight/obesity observed between HIV-negative and HIV-positive patients may suggest that the two groups shared the same exposure factors. That HTN and DM/CHD prevalence was lower among HIV-positive compared to HIV-negative patients, is possibly due to interplay factors of ART, HIV or the host population. Further studies are, however, recommended for clarifications.

Prevalence and Factors Associated with Overweight and Obesity among Public Secondary School Teachers in Parakou, Benin, in 2021

Introduction: Overweight and obesity represent a public health problem in Africa due to the epidemiological transition. The objectives of this work were to determine the prevalence of overweight and obesity and to identify associated factors among public secondary school teachers in Parakou, Benin in 2021. Methods: We conducted a descriptive and analytical cross-sectional study. Teachers working in public secondary schools in Parakou during the 2020-2021 academic year, present at work and who gave their written informed consent, were included. A two-stage random sampling was carried out. Data were collected during an individual interview using a questionnaire followed by the measurement of anthropometric parameters and blood pressure. Overweight and obesity were defined by a body mass index ≥ 25 kg/m2. Multivariable logistic regression was performed to identify associated factors. Results: A sample of 325 teachers, including 88.6% of men, was recruited with an average age of 36.2 ± 6.8 years. The prevalence of overweight and obesity was 43.7% (95% CI [38.1%-44.8%]). It increased significantly with income (p Conclusion: The results show a high prevalence of overweight and obesity. Actions are necessary to prevent overweight and obesity among secondary school teachers in Parakou, in Benin.

Association of Serum Folate and Vitamin B_(12) Concentrations with Obesity in Chinese Children and Adolescents

Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and adolescents.Methods A cross-sectional study was conducted including 3,079 Chinese children and adolescents,aged 6 to 17 years,from Jiangsu,China.Anthropometric indices,such as,children's body mass index(BMI),BMI z-scores,waist circumference,and waist-to-height ratio were utilized.Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B12 levels with anthropometric indices and odds of obesity.Results We observed that serum vitamin B12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity[odds ratio(OR)=0.68;95%confidence interval(CI)=0.59,0.78]and abdominal obesity(OR=0.68;95%CI=0.60,0.77).When compared to participants with both serum vitamin levels in the two middle quartiles,those with both serum folate and vitamin B12 levels in the highest quartile were less prone to general(OR=0.31,95%CI=0.19,0.50)or abdominal obesity(OR=0.46,95%CI=0.31,0.67).Conversely,participants with vitamin B12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity(OR=2.06,95%CI=1.09,3.91).Conclusion Higher serum vitamin B12 concentrations,but not serum folate concentrations,were associated with lower odds of childhood obesity.Children and adolescents with high levels of vitamin B12 and folate were less likely to be obese.

Carbonic anhydrase 2 mediates anti-obesity effects of black tea as thermogenic activator

Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strategy of anti-obesity by dissipating energy as heat.However,drugs based on adipose tissue thermogenesis have not been successfully approved yet.In current study,we found that black tea extract(BTE)obtained by patentauthorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity,improvement of adipose distribution,and glucose metabolism improvement in diet-induced obesity mice.Mechanismly,anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1(UCP1),especially visceral adipose tissue(VAT)with browning resistance.Specifically,utilizing in silico approach of network pharmacology and molecular docking,we identified carbonic anhydrase 2(CA2)in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B(AKT)signaling pathway linked CA2 and UCP1.Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation.Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway,which could be developed as promising anti-obesity agent with good safety and efficacy.

Transcriptome analysis suggests broad jejunal alterations in Linghu’s obesity-diarrhea syndrome:A pilot study

BACKGROUND Obesity is associated with a significantly increased risk for chronic diarrhea,which has been proposed as Linghu’s obesity-diarrhea syndrome(ODS);however,its molecular mechanisms are largely unknown.AIM To reveal the transcriptomic changes in the jejunum involved in ODS.METHODS In a cohort of 6 ODS patients(JOD group),6 obese people without diarrhea(JO group),and 6 healthy controls(JC group),high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological processes.In another cohort of 16 ODS patients(SOD group),16 obese people without diarrhea(SO group),and 16 healthy controls(SC group),serum diamine oxidase(DAO)and D-lactate(DLA)concentrations were detected to assess changes in intestinal barrier function.RESULTS The gene expression profiles of jejunal mucosa in the JO and JC groups were similar,with only 1 differentially expressed gene(DEG).The gene expression profile of the JOD group was significantly changed,with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group,129 of which overlapped.The enrichment analysis of these DEGs showed that the biological processes such as digestion,absorption,and transport of nutrients(especially lipids)tended to be up-regulated in the JOD group,while the biological processes such as rRNA processing,mitochondrial translation,antimicrobial humoral response,DNA replication,and DNA repair tended to be down-regulated in the JOD group.Eight DEGs(CDT1,NHP2,EXOSC5,EPN3,NME1,REG3A,PLA2G2A,and PRSS2)may play a key regulatory role in the pathological process of ODS,and their expression levels were significantly decreased in ODS patients(P<0.001).In the second cohort,compared with healthy controls,the levels of serum intestinal barrier function markers(DAO and D-LA)were significantly increased in all obese individuals(P<0.01),but were higher in the SOD group than in the SO group(P<0.001).CONCLUSION Compared with healthy controls and obese individuals without diarrhea,patients with Linghu’s ODS had extensive transcriptomic changes in the jejunal mucosa,likely affecting intestinal barrier function and thus contributing to the obesity and chronic diarrhea phenotypes.

Female Infertility and Obesity across the United States—A Geographic Cross-Sectional Analysis

This cross-sectional study investigates a connection between female infertility and obesity across various regions of the United States, utilizing data from the NIH’s “All of Us” Researcher Workbench. Analysis suggested that the Southern region exhibited the highest percentage of concurrently infertile and obese females at 32.3%, in contrast to the lowest in the Western region at 28.7%. The findings underscore the significant regional disparities in obesity-related infertility, particularly in medically underserved areas where healthcare access is limited. The study highlights the urgent need for targeted public health interventions, particularly in the Southern United States, to address the rising prevalence of obesity and its impact on infertility. Further, these results advocate for enhanced public health education and policies aimed at improving healthcare accessibility, with the goal of mitigating the adverse effects of obesity on reproductive health.

Insights into the interplay between gut microbiota and lipid metabolism in the obesity management of canines and felines

Obesity is a prevalent chronic disease that has significant negative impacts on humans and our companion animals,including dogs and cats.Obesity occurs with multiple comorbidities,such as diabetes,hypertension,heart disease and osteoarthritis in dogs and cats.A direct link between lipid metabolism dysregulation and obesity-associated diseases has been implicated.However,the understanding of such pathophysiology in companion animals is lim-ited.This review aims to address the role of lipid metabolism in various metabolic disorders associated with obesity,emphasizing the involvement of the gut microbiota.Furthermore,we also discuss the management of obesity,including approaches like nutritional interventions,thus providing novel insights into obesity prevention and treatment for canines and felines.

Akkermansia muciniphila-directed polyphenol chlorogenic acid intervention for obesity in mice

Akkermansia muciniphila play an important in ameliorating obesity but is not allowed for direct consumption in most countries.To date,microbiota-directed foods selectively promote the targeted human gut microbes,providing a strategy for A.muciniphila enhancement.Multiple studies have indicated the potential regulation of the polyphenol on A.muciniphila.Therefore,a polyphenol screening based on A.muciniphila upregulation was performed in mice.Chlorogenic acid(CGA)exhibited a greater response to A.muciniphila upregulation.Furthermore,we found that CGA did not directly promote A.muciniphila growth or mucin secretion.Microbiome and metabolomics revealed that the increased abundance of A.muciniphila resulted from the inhibition of CGA on Desulfovibrio and Alistipes and the influence of docosahexaenoic acid,β-hydroxybutyrate,and N-acetyl-lactosamine.Finally,to confirm the regulation of CGA on A.muciniphila under disease conditions,high-fat diet-fed mice were established.The results showed CGA promoted A.muciniphila growth,and we expectedly found that CGA suppressed the augment in body weight of mice,significantly attenuated adipose tissue abnormality,provided liver protection and improved gut barrier integrity.These results suggest that CGA inhibits the development of obesity.Overall,our results indicate that microbiota-directed food is a promising approach for the treatment of obesity.

Polysaccharides of Aspergillus cristatus attenuate obesity by regulating gut microbiota and gut microbiota-related metabolites

Golden-flower fungus,the only dominant microorganism determining the Fu-brick tea quality through fermentation and the important microbe in Liupao tea,is considered a potential probiotic fungus based on its anti-obesity effect.However,the classification of golden-flower fungi is still controversial;the anti-obesity effect of golden-flower fungus polysaccharides remains unknown.In this study,we identify a golden-flower strain as Aspergillus cristatus based on morphological characteristics and multigene phylogeny analysis,which resolves the controversy of classification.Moreover,we find A.cristatus polysaccharides(ACPS)attenuate obesity in rats.ACPS modulate gut bacterial composition.in which Akkermansia,Akkermansia muciniphila,Bacteroides,Romboutsia,Blautia,and Desulfovibrio are considered the core microbes regulated by ACPS.ACPS increase fecal total short-chain fatty acid content and serum,hepatic,and fecal total bile acid content.Furthermore,ACPS-induced gut microbiota alteration plays a causal role in the protection from obesity,according to a fecal transplantation experiment.Thus,ACPS ameliorate obesity by regulating gut microbiota and gut microbiota-related metabolites.

Overweight/Obesity in University Students from Mexico: Comparison Using Different Indices

The goal was to compare body mass index (BMI), waist circumference (WC), waist to height ratio (WHtR), and relative fat mas (RFM), to identify the best predictor of overweight and obesity in university students from Mexico. This is a cross-sectional survey with 697 university students from northern and central Mexico (448 women, and 249 men aged 18 - 19 years). Data was collected during 2018. Overweight and obesity were calculated from those indices and for both, female and male students, the order of correlation between a pair of indices were WHtR vs. RFM > WHtR vs. WC > RFM vs. WC > WHtR vs. BMI > BMI vs. WC > RFM vs. BMI. It is concluded to use the WHtR and the RFM to better predict overweight and obesity in young Mexican university students.

Mechanism of Wendan decoction in preventing obesity by regulating multiple signal pathway networks based on gene promoter methylation

Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promoter methylation.Methods:The methylation degree of Itgad,Col8a1,Adra2b,Jund,Rab2a,Wnt8b,Fzd9,B4galt7,Pik3cd,Creb1,Stard8,and Mmp1 in the abdominal adipose tissue of obese rats was determined using the Agena MassARRAY system.Western blot was performed to assess protein expression levels.Target genes were identified based on the methylation degree in the promoter region and protein expression.Enrichment analysis of signaling pathways was conducted to identify relevant target genes and obtain a multiple signaling pathway network associated with obesity.Core and terminal effector molecules in the pathway networks were selected as research targets for reverse transcription-polymerase chain reaction(RT-PCR)analysis.Results:Four genes(Adra2b,Creb1,Itgad,and Pik3cd)showed a degree of promoter methylation consistent with their respective protein expression levels.Among them,Adra2b,Creb1,and Pik3cd expression increased,while that of Itgad decreased.Enrichment analysis revealed that Creb1 and Pik3cd were involved in 6 signaling pathways related to obesity:tumor necrosis factor(TNF)signaling pathway,growth hormone synthesis/secretion and action,adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,relaxin signaling pathway,cyclic nucleotide(cAMP)signaling pathway,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Subsequently,a multiple signaling pathways network was constructed based on promoter methylation.Key molecules including protein kinase B(AKT),mechanistic target of rapamycin complex 1(mTORC1),and unc-51 like autophagy activating kinase 1(ULK1),as well as terminal effector molecules interleukin-1β(IL-1β),interleukin-6(IL-6),and chemokine(C-X-C motif)ligand 2(CXCL2)were selected as research targets.Wendan decoction decreased the expressions of AKT,mTORC1,IL-1β,IL-6,and CXCL2 while up-regulating ULK1 expression.Conclusion:The mechanism of Wendan decoction in preventing obesity involves the regulation of multiple signaling pathways through the control of Creb1 and Pik3cd gene promoter methylation.However,the associated multi-path gene regulation mechanism in preventing obesity is complex.Thus,further exploration is needed to elucidate the role of methylation changes in this mechanism.