Aging leads to a programmed loss of brown adipocytes in murine subcutaneous white adipose tissue

Insulin sensitivity deteriorates with age, but mechanisms remain unclear. Age‐related changes in the function of subcutaneous white adipose tissue () are less characterized than those in visceral WAT. We hypothesized that metabolic alterations in , which in contrast to epididymal WAT, harbors a subpopulation of energy‐dissipating UCP1+ brown adipocytes, promote age‐dependent progression toward insulin resistance. Indeed, we show that a predominant consequence of aging in murine is loss of ‘browning’. from young mice is histologically similar to brown adipose tissue (multilocular, UCP1+), but becomes morphologically white by 12 months of age. Correspondingly, expression of precipitously declines (~300‐fold) between 3 and 12 months. Loss continues into old age (24 months) and is inversely correlated with the development of insulin resistance. Additional age‐dependent changes in include lower expression of and higher expression of , suggesting reduced local adrenergic tone as a potential mechanism. Indeed, treatment with a β3‐adrenergic agonist to compensate for reduced tone rescues the aged phenotype. Age‐related changes in are not explained by the differences in body weight; mice subjected to 40% caloric restriction for 12 months are of body weight similar to 3‐month‐old fed mice, but display resembling that of age‐matched fed mice (devoid of brown adipose‐like morphology). Overall, findings identify the loss of ‘browning’ in as a new aging phenomenon and provide insight into the pathogenesis of age‐associated metabolic disease by revealing novel molecular changes tied to systemic metabolic dysfunction.

Duke Scholars

Author Alejandro Landa Obstetrics and Gynecology, Harris & Smith OB-GYN