Editors' ChoiceObesity

Nature vs. nurture in adipocyte responses to high-fat feeding

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Science Translational Medicine  20 Jul 2016:
Vol. 8, Issue 348, pp. 348ec116
DOI: 10.1126/scitranslmed.aah3549

Complications related to obesity depend not only on absolute adiposity but also on fat distribution. Intra-abdominal (visceral) and subcutaneous adipose tissues differ in their genetic, metabolic, and secretory profiles, and their responses to excess calories. Increased visceral adipose tissue increases cardiovascular risk, but subcutaneous adipose tissue reduces metabolic risk. Visceral adiposity is more common in males, but subcutaneous adiposity is more frequent in females. Now, Jeffery et al. have begun to examine the mechanisms of site-specific adipocyte responses to excess calories.

First, the authors confirmed the effects of high-fat diet on adipose tissue. Increased calories increased adipocyte size but also stimulated adipocyte precursor (AP) proliferation, thereby increasing adipocyte number. In a similar manner to humans, these responses occurred primarily in the visceral fat in male mice but in both intra-abdominal and subcutaneous fat in females and in all the fat depots where AP proliferation was seen, it correlated with fat pad weight. Next, the researchers showed that estrogen removal from female mice reduced subcutaneous AP proliferation, whereas estrogen treatment in male mice increased it. Last, the authors examined whether the variation in AP proliferation at different sites was due to AP cell–intrinsic differences or the local environment. AP cells isolated from either intra-abdominal or subcutaneous fat transplanted into the intra-abdominal or subcutaneous fat of male or female mice responded to high-fat feeding consistent with the host microenvironment rather than the donor tissue.

This study shows that adipocyte precursor proliferation in response to high-fat feeding is not fixed but varies with the hormonal milieu and the immediate environment. These findings suggest that local signals may regulate the site of AP replication and in turn influence the changes in fat distribution that occur with excess calories. If similar signals are present in humans, modulating such pathways might offer an approach to redistribute adiposity from a higher risk visceral distribution to lower risk subcutaneous adiposity.

E. Jeffery et al., The adipose tissue microenvironment regulates depot-specific adipogenesis in obesity. Cell Metab. 24, 142–150 (2016). [Abstract]

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