MicroRNAs (miRNAs) are endogenous small RNAs that posttranscriptionally regulate gene expression and that have been shown to have important roles in numerous disease processes. There is growing evidence for an important role of miRNAs in regulating the pathways in adipose tissue that control a range of processes including adipogenesis, insulin resistance and inflammation. Several high-throughput studies have identified differentially expressed miRNAs in adipose tissue pathology and during adipogenesis and a number of these have now been characterised functionally in terms of their actions and targets. This review will summarise the current literature on miRNAs in adipose tissue, as well as discussing the methodologies used in this area of research and the potential application of miRNAs as biomarkers and as therapeutic targets.

Upper-body adiposity is associated with increased metabolic disease risk, while lower-body adiposity is paradoxically protective. Efforts to understand the underlying mechanisms require appropriate and reproducible in vitro culture models. We have therefore generated immortalised (im) human preadipocyte (PAD) cell lines derived from paired subcutaneous abdominal and gluteal adipose tissue. These cell lines, denoted imAPAD and imGPAD display enhanced proliferation and robust adipogenic capacities. Differentiated imAPAD and imGPAD adipocytes synthesize triglycerides de novo and respond lipolytically to catecholamine-stimulation. Importantly the cells retain their depot-of-origin ‘memory’ as reflected by inherent differences in fatty acid metabolism and expression of depot-specific developmental genes. These features make these cell lines an invaluable tool for the in vitro investigation of depot-specific human adipocyte biology.

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A bidirectional relationship exists between adipose tissue metabolism and iron regulation. Total body fat, fat distribution and exercise influence iron status and components of the iron-regulatory pathway, including hepcidin and erythroferrone. Conversely, whole body and tissue iron stores associate with fat mass and distribution and glucose and lipid metabolism in adipose tissue, liver, and muscle. Manipulation of the iron-regulatory proteins erythroferrone and erythropoietin affects glucose and lipid metabolism. Several lines of evidence suggest that iron accumulation and metabolism may play a role in the development of metabolic diseases including obesity, type 2 diabetes, hyperlipidaemia and non-alcoholic fatty liver disease. In this review we summarise the current understanding of the relationship between iron homoeostasis and metabolic disease.

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 and (G1001959) and . We acknowledge the OBB-NIHR (BHF) (RG/17/1/32663). Work performed at the MRC Epidemiology Unit was funded by the through grants MC_UU_12015/1, MC_PC_13046, MC_PC_13048 and MR/L00002/1.

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Background: Body composition is associated with bone mineral density (BMD), but the precise associations between body fat distribution and BMD remain unclear. The regional adipose tissue depots have different metabolic profiles. We hypothesized that they would have independent associations with BMD.Research Design and Methods: We used data from 4,900 healthy individuals aged 30-50 years old from the Oxford Biobank to analyze associations between regional fat mass, lean mass and total BMD. Results: Total lean mass was strongly positively associated with BMD. An increase in total BMD was observed with increasing mass of all the fat depots, as measured either by anthropometry or DXA, when accounting for lean mass. However, on adjustment for both total fat mass and lean mass, fat depot specific associations emerged. Increased android and visceral adipose tissue mass in men, and increased visceral adipose tissue mass in women, were associated with lower BMD. Conclusions: Fat distribution alters the association between adiposity and BMD.