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MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix composition.

ABSTRACT: BACKGROUND:Abdominal fat mass is associated with metabolic risk whilst gluteal femoral fat is paradoxically protective. MicroRNAs are known to be necessary for adipose tissue formation and function but their role in regulating human fat distribution remains largely unexplored. METHODS:An initial microarray screen of abdominal subcutaneous and gluteal adipose tissue, with validatory qPCR, identified microRNA-196a as being strongly differentially expressed between gluteal and abdominal subcutaneous adipose tissue. FINDINGS:We found that rs11614913, a SNP within pre-miR-196a-2 at the HOXC locus, is an eQTL for miR-196a expression in abdominal subcutaneous adipose tissue (ASAT). Observations in large cohorts showed that rs11614913 increased waist-to-hip ratio, which was driven specifically by an expansion in ASAT. In further experiments, rs11614913 was associated with adipocyte size. Functional studies and transcriptomic profiling of miR-196a knock-down pre-adipocytes revealed a role for miR-196a in regulating pre-adipocyte proliferation and extracellular matrix pathways. INTERPRETATION:These data identify a role for miR-196a in regulating human body fat distribution. FUND: This work was supported by the Medical Research Council and Novo Nordisk UK Research Foundation (G1001959) and Swedish Research Council. We acknowledge the OBB-NIHR Oxford Biomedical Research Centre and the British Heart Foundation (BHF) (RG/17/1/32663). Work performed at the MRC Epidemiology Unit was funded by the United Kingdom's Medical Research Council through grants MC_UU_12015/1, MC_PC_13046, MC_PC_13048 and MR/L00002/1.

SUBMITTER: Hilton C

PROVIDER: S-EPMC6607082 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix composition.

Hilton Catriona C Neville Matt J MJ Wittemans Laura B L LBL Todorcevic Marijana M Pinnick Katherine E KE Pulit Sara L SL Luan Jian'an J Kulyté Agné A Dahlman Ingrid I Wareham Nicholas J NJ Lotta Luca A LA Arner Peter P Lindgren Cecilia M CM Langenberg Claudia C Karpe Fredrik F

EBioMedicine 20190528

<h4>Background</h4>Abdominal fat mass is associated with metabolic risk whilst gluteal femoral fat is paradoxically protective. MicroRNAs are known to be necessary for adipose tissue formation and function but their role in regulating human fat distribution remains largely unexplored.<h4>Methods</h4>An initial microarray screen of abdominal subcutaneous and gluteal adipose tissue, with validatory qPCR, identified microRNA-196a as being strongly differentially expressed between gluteal and abdomi ...[more]

PMID: 31151930

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Project description:BackgroundAdipose tissue may have different metabolic and endocrine functions depending on the region of the body in which it is located. While visceral or intra-abdominal fat has been found to contribute to leptin concentrations, insulin resistance and obesity-related diseases, there are only a few imaging studies documenting the preferential distribution of body fat to either the intra-abdominal or subcutaneous compartments in dogs. This study aimed to determine if CT-measured abdominal fat distributed preferentially to the visceral space (V) relative to the subcutaneous space (SQ), with increasing DXA-determined total body fat percentage; and if ultrasound measurements of the ventral midline subcutaneous (SAT) and visceral adipose thickness (VAT) can be used to estimate the distribution of fat to the subcutaneous and visceral abdominal spaces, in a sample of 22 dogs with variable body condition.ResultsMultivariate analysis showed no statistically significant correlation between visceral to subcutaneous fat ratio (V/SQ) and increasing total body fat percentage (??=???0.07, p?=?0.733), but strong correlation with age (??=?0.71 p?=?0.002). A substantial amount of variation for the ultrasound visceral adipose thickness to subcutaneous fat thickness (VAT/SAT) could be explained by both CT V/SQ and sex (R2Adjusted?=?0.477, p?=?0.001), with female dogs having significant lower VAT/SAT ratios compared to the male dogs (p?=?0.047). The ultrasound fat measurements appeared moderately reliable, but a larger sample number is required to confirm this.ConclusionsThe findings suggest that dogs with a relatively healthy to slightly overweight body condition score, distribute fat relatively similarly between their peritoneal (visceral) and subcutaneous abdominal compartments with increasing total body fat percentage. However, there was increased fat distribution to the peritoneal space relative to the subcutaneous space with increasing age. Further, abdominal ultrasound may be useful in estimating the ratio of fat distribution to both the abdominal visceral and subcutaneous spaces.

Dataset Information

MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix composition.

Publications

MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix composition.

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