Editors' ChoiceMetabolic Disease

Faulty fat cells linked to weight gain

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Science Translational Medicine  27 Jun 2018:
Vol. 10, Issue 447, eaau1970
DOI: 10.1126/scitranslmed.aau1970

Abstract

Altered fat cell lipolysis predicts long-term weight gain and risk of type 2 diabetes.

Global rates of obesity and type 2 diabetes continue to rise and are driven by environmental factors including unhealthy diets and physical inactivity. But what makes some people more susceptible to weight gain than others even when they are exposed to similar environments? A new study by Arner and colleagues provides evidence to suggest that inefficient adipocyte lipolysis may play a role.

The investigators used data collected from two prospective cohort studies, including measurements of body weight and fat biopsies taken at the beginning and end of studies over a period of 12 to16 years. They divided women into two groups: those who gained weight and those who remained weight stable. Women who lost weight were excluded from analysis. These biopsies of adipocytes (fat cells) were examined for their ability to mobilize fatty acids, a process called lipolysis in which adipocytes are broken down and fatty acids are released for energy. Women whose adipocytes had higher spontaneous lipolysis but were less responsive to hormone-stimulated lipolysis gained significantly more weight and had higher incidence of subsequent type 2 diabetes development. The adipocytes of weight gainers also displayed lower expression of genes involved in the regulation of lipolysis at baseline.

Based on these findings, the researchers developed an algorithm for estimating hormone-stimulated lipolysis from standard clinical measurements, including body weight and blood tests. They showed that low hormone–stimulated lipolysis could be accurately estimated using the algorithm instead of tissue biopsies. Future studies are needed to validate this method in larger groups of people.

Collectively, these findings suggest that inefficient lipolysis caused by alterations in adipocyte gene expression can predict future weight gain and greater risk of type 2 diabetes development, at least in women. This could help identify people who may benefit from targeted lifestyle interventions such as aerobic exercise programs, which have been shown to enhance fat lipolysis.

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