Dataset Information

Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population.

ABSTRACT: Genome-wide association studies (GWAS) have uncovered numerous variants associated with body mass index (BMI), waist circumference, and waist-to-hip ratio. Our study aims to investigate how these variants are linked to fat distribution. We genotyped 56 validated variants of BMI, waist circumference, and waist-to-hip ratio in 2958 subjects from Chinese community-based populations and performed linear regression analyses to determine the association with visceral fat area (VFA) and subcutaneous fat area (SFA) imaged by magnetic resonance imaging (MRI). We found rs671 in ALDH2 exhibited the significant associations with VFA and the VFA-SFA ratio in all subjects (P?=?9.64?×?10(-5) and 6.54?×?10(-4)). rs17782313 near MC4R for VFA and rs4846567 near LYPLAL1 for SFA were found in females only (P?=?2.93?×?10(-4) and 0.0015), whereas rs671 in ALDH2 for VFA and the VFA-SFA ratio was restricted to males (P?=?1.75?×?10(-8) and 4.43?×?10(-8)). Given the robust association of rs671 with alcohol consumption, we next demonstrated the primary effects of rs671 on VFA and the VFA-SFA ratio were restricted to drinkers (P?=?1.45?×?10(-4) and 4.65?×?10(-3)). Our data implied that variants of MC4R and LYPLAL1 modulated body fat distribution with sexual dimorphism and that alcohol consumption may mediate the impact of the ALDH2 locus on visceral fat in a Chinese population.

SUBMITTER: Wang T

PROVIDER: S-EPMC4742921 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population.

Wang Tao T Ma Xiaojing X Peng Danfeng D Zhang Rong R Sun Xue X Chen Miao M Yan Jing J Wang Shiyun S Yan Dandan D He Zhen Z Jiang Feng F Bao Yuqian Y Hu Cheng C Jia Weiping W

Scientific reports 20160205

Genome-wide association studies (GWAS) have uncovered numerous variants associated with body mass index (BMI), waist circumference, and waist-to-hip ratio. Our study aims to investigate how these variants are linked to fat distribution. We genotyped 56 validated variants of BMI, waist circumference, and waist-to-hip ratio in 2958 subjects from Chinese community-based populations and performed linear regression analyses to determine the association with visceral fat area (VFA) and subcutaneous fa ...[more]

PMID: 26848030

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Project description:As a serious public health problem nowadays, obesity and its complications are receiving gradually more attention, especially on how food-induced obesity causes the expansion of adipose tissue and leads to the occurrence of metabolic inflammation and infiltration of immune cells. It's still worth mentioning that numerous genes in adipose tissue which differ between obese and normal individuals in food-induced obesity were not insufficiently studied. Applying machine learning methods and natural language processing methods on transcriptome datasets and PubMed abstracts, we investigated 8 genes with differential expression and high association with macrophages in the visceral and subcutaneous adipose tissue between obese and normal individuals, and meanwhile low correlation with leptin. Compared with normal group, Quantitative Real-time Polymerase Chain Reaction, Western Blot, immunohistochemistry, immunofluorescence and other subsequent animal experiments on the 8 filtered genes were applied in the adipose tissue of C57BL/6J and OB/OB mice, we found that the expression of glycoprotein IX (GP9), MHC class I polypeptide related sequence B (MICB), CDGSH iron sulfur domain 1 (CISD1) and Pre-mRNA-processing factor 19 (PRPF19) in protein level were down-regulated in visceral fat of obese mice induced by high-fat diet. And these obese mice showed decreased levels of mannosidase alpha class 2B member 1 (MAN2B1) and TYRO protein tyrosine kinase binding protein (TYROBP) in their subcutaneous adipose tissue, while phosphate and tension homology deleted on chromosome pten (PTEN) and eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) had been sufficiently studied. The pattern in OB/OB mouse was dramatically different with these patterns. Through double immunofluorescence staining, it was found that all genes were co-localized with CD206, which was the marker of M1 and M2 macrophage in adipose tissue. Further interacting drugs for the genes were calculated and subsequently circumin and beta-catonin were proved to be interacting with these genes and functioned in inhibiting food-induced obesity. Further knowledge gragh was constructed to illustrate the relationship between obesity, filtered genes, drugs and related concepts. To summarize our findings, we discovered some new differential genes in adipose tissue which could potentially establish a new connection between adipose tissue macrophages and food-induced obesity. Furthermore, they offered unique insights into exploring the mechanism of adipose tissue genes related to food-induced obesity and related diseases.

Project description:Adipose tissue plays a critical role in energy homeostasis and metabolism. There is sparse understanding of the molecular regulation at the protein level of bovine adipose tissues, especially within different fat depots under different nutritional regimes. The objective of this study was to analyze the differences in protein expression between bovine subcutaneous and visceral fat depots in steers fed different diets and to identify the potential regulatory molecular mechanisms of protein expression. Subcutaneous and visceral fat tissues were collected from 16 British-continental steers (15.5 month old) fed a high-fat diet (7.1% fat, n=8) or a control diet (2.7% fat, n=8). Protein expression was profiled using label free quantification LC-MS/MS and expression of selected transcripts was evaluated using qRT-PCR. A total of 682 proteins were characterized and quantified with fat depot having more impact on protein expression, altering the level of 51.0% of the detected proteins, whereas diet affected only 5.3%. Functional analysis revealed that energy production and lipid metabolism were among the main functions associated with differentially expressed proteins between fat depots, with visceral fat being more metabolically active than subcutaneous fat as proteins associated with lipid and energy metabolism were upregulated. The expression of several proteins was significantly correlated to subcutaneous fat thickness and adipocyte size, indicating their potential as adiposity markers. A poor correlation (r=0.245) was observed between mRNA and protein levels for 9 genes, indicating that many proteins may be subjected to post-transcriptional regulation. A total of 8 miRNAs were predicted to regulate more than 20% of lipid metabolism proteins differentially expressed between fat depots, suggesting that miRNAs play a role in adipose tissue regulation. Our results show that proteomic changes support the distinct metabolic and physiological characteristics observed between subcutaneous and visceral adipose tissue depots in cattle.

Dataset Information

Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population.

Publications

Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population.

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