Adipose tissue is the primary organ storing energy, which includes white, brown and beige adipocytes. White fat could convert into brown fat-like containing UCP1-positive cells (beige adipocyte) under external stimulation such as cold, a process known as white fat browning.
According to previous studies, brown adipose tissue (BAT) acquires white adipose tissue (WAT) cell features defined as BAT whitening under certain circumstances. The nature of BAT whitening and its mechanisms, however, remain poorly understood.
Recently, a study revealed that autophagy inhibition prevents glucocorticoid-increased adiposity via suppressing BAT whitening.
Glucocorticoids (GCs) are a class of steroid hormones and exert effects by binding to the glucocorticoid receptor. GC and their synthetic analogs, such as dexamethasone (Dex), are widely used to treat various diseases.
Unfortunately, their side effects limit the long-term use of GCs. One of such effects is the increased adiposity in WAT. Understanding the mechanisms underlying GC-increased adiposity will help to develop more effective clinical application.
In this study, researchers showed that fat mass content and WAT weight were increased in mice treated with Dex for one week. Meanwhile, they found that one-week Dex treatment induced BAT whitening, characterized by the accumulation of enlarged lipid droplets and increased lipid contents.
In addition, UCP1 expression and oxygen consumption rate were decreased in BAT cells of Dex-treated mice. Furthermore, ATG7 (autophagy related 7) expression and autophagy were induced in BAT by Dex.
Autophagy plays a wide variety of physiological and pathophysiological roles. It is a cellular process that degrades intracellular organelles and proteins via autophagy-related genes. Treatment with the autophagy inhibitor chloroquine or adenovirus-mediated ATG7 knockdown prevented Dex-induced BAT whitening and fat mass gain.
Moreover, Dex-increased ATG7 expression and autophagy were mediated by BTG1 (B cell translocation gene 1, anti-proliferative)/CREB1 (cAMP response element binding protein 1) signaling.
The importance of BTG1 in this regulation was further demonstrated by the observed BAT whitening in adipocyte-specific BTG1- overexpressing mice. BTG1 knockdown in BAT attenuated Dex-induced BAT whitening and fat mass gain.
The study showed that Dex induces a significant whitening of BAT via BTG1- and ATG7-dependent autophagy, which might contribute to Dex-increased adiposity.
These results published in Autophagy provide new insights into the mechanisms underlying GC-increased adiposity and possible strategy for preventing GC-induced side effects via the combined use of an autophagy inhibitor.
Role of Autophagy in Glucocorticoid-Induced BAT Whitening
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