Genome affects where fat is stored in body, new study says

A recent study from Uppsala University in Sweden has found that whether you store your fat around the trunk or in other parts of your body is highly influenced by genetic factor. This effect is present predominantly in women and to a much lower extent in men, according to the new research, which was published yesterday in Nature Communications.

Body mass and body fat composition are of clinical interest due to their links to cardiovascular and metabolic diseases. Fat stored in the trunk has been suggested to be more pathogenic compared to fat stored in other compartments.

In this study, researchers performed genome-wide association studies (GWAS) for the proportion of body fat distributed to the arms, legs, and trunk estimated from segmental bio-electrical impedance analysis (sBIA) for 362,499 individuals from the UK Biobank, a cohort study of half a million participants in the UK. The participants gave blood samples for genotyping and the distribution of fat tissue was estimated using impedance measurements.

In the current study, millions of genetic variants across the genome were tested for association with distribution of fat to the arms, legs or trunk, and the research team identified nearly a hundred genes that affect distribution of adipose tissue to the different compartments of the human body. Researchers identified 98 independent associations with body fat distribution, including 29 that have not previously been associated with anthropometric traits.

A high degree of sex-heterogeneity was observed, and the effects of 37 associated variants are stronger in females compared to males. The findings also implicate that body fat distribution in females involves mesenchyme derived tissues and cell types, female endocrine tissues as well as extracellular matrix maintenance and remodeling.

It is commonly known that women and men tend to store fat differently, according to Mathias Rask-Andersen, PhD, postdoctoral researcher at the department of immunology, genetics, and pathology at Uppsala University.

"This has been attributed to the effects of sex hormones such as estrogen,” said Rask-Andersen. “But the molecular mechanisms that control this phenomenon are fairly unknown."

Researchers were struck by the large number of genetic effects that were stronger, or only present, in females, according to Åsa Johansson, PhD, lead researcher and associate senior lecturer.

“Upon closer examination, several of the associated genes were found to encode proteins that actively shape the extracellular matrix, which makes up the supporting structure around cells," she says. “The findings suggest that remodeling of the extracellular matrix is one of the mechanisms that generates differences in body fat distribution.”

Fat stored in the trunk has previously been associated with increased disease risk. Men have a greater amount of abdominal fat than women and this may explain the increased prevalence of cardiovascular disease observed in males. Epidemiological studies have even shown that the ability to store fat around hips and legs gives women some protection against cardiovascular disease. The result of the current study may therefore lead to the development of new interventions to reduce the risk of cardiovascular disease.

"The biological systems we highlight in our study,” says says Mathias Rask-Andersen, “have the potential to be used as points-of-intervention for new drugs that are aimed at improving the distribution of body fat and thereby reducing the risk of disease.”