Brown fat whitening

Brown adipose tissue (BAT) is a highly vascularized tissue that provides heat for newborn babies and was thought to disappear with age; however, recent studies have shown that BAT in adults contributes to overall metabolic capacity. Furthermore, dysfunctional BAT has been linked to obesity; however, it is not clear how the obese state promotes BAT alterations. Ippei Shimizu and colleagues at Boston University School of Medicine used a murine model of diet-induced obesity to evaluate changes in BAT and determined that obesity leads to a “whitening” phenotype in BAT that is characterized by reduced capillary volume, hypoxia, mitochondrial dysfunction, increased lipid droplet accumulation, and reduced Vegfa expression. In non-obese mice, reduction of VEGF-A in adipose tissue promoted BAT whitening, while induction of VEGF-A expression in BAT of obese mice increased vascularity, restored adipocyte function, and improved insulin response. Together, these results indicate that reduced vascularity precipitates obesity-associated BAT phenotypes and link BAT whitening with alterations in glucose metabolism. The accompanying image shows immunofluorescent staining of adipocytes (red) and blood vessels in BAT (top row) and white adipose tissue (bottom row) in animals fed a normal diet (left column) and animals fed a high fat diet (right column). There is a noticeable reduction of vascularity in adipose tissue of animals on a high-fat diet.

Published April 8, 2014, by Corinne Williams

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Vascular rarefaction mediates whitening of brown fat in obesity
Ippei Shimizu, Tamar Aprahamian, Ryosuke Kikuchi, Ayako Shimizu, Kyriakos N. Papanicolaou, Susan MacLauchlan, Sonomi Maruyama, Kenneth Walsh
Ippei Shimizu, Tamar Aprahamian, Ryosuke Kikuchi, Ayako Shimizu, Kyriakos N. Papanicolaou, Susan MacLauchlan, Sonomi Maruyama, Kenneth Walsh
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Research Article Endocrinology

Vascular rarefaction mediates whitening of brown fat in obesity

Abstract

Brown adipose tissue (BAT) is a highly vascularized organ with abundant mitochondria that produce heat through uncoupled respiration. Obesity is associated with a reduction of BAT function; however, it is unknown how obesity promotes dysfunctional BAT. Here, using a murine model of diet-induced obesity, we determined that obesity causes capillary rarefaction and functional hypoxia in BAT, leading to a BAT “whitening” phenotype that is characterized by mitochondrial dysfunction, lipid droplet accumulation, and decreased expression of Vegfa. Targeted deletion of Vegfa in adipose tissue of nonobese mice resulted in BAT whitening, supporting a role for decreased vascularity in obesity-associated BAT. Conversely, introduction of VEGF-A specifically into BAT of obese mice restored vascularity, ameliorated brown adipocyte dysfunction, and improved insulin sensitivity. The capillary rarefaction in BAT that was brought about by obesity or Vegfa ablation diminished β-adrenergic signaling, increased mitochondrial ROS production, and promoted mitophagy. These data indicate that overnutrition leads to the development of a hypoxic state in BAT, causing it to whiten through mitochondrial dysfunction and loss. Furthermore, these results link obesity-associated BAT whitening to impaired systemic glucose metabolism.

Authors

Ippei Shimizu, Tamar Aprahamian, Ryosuke Kikuchi, Ayako Shimizu, Kyriakos N. Papanicolaou, Susan MacLauchlan, Sonomi Maruyama, Kenneth Walsh

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