Molecular clock integration of brown adipose tissue formation and function

Abstract

The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation.

KEYWORDS:

• adipogenesis
• brown adipose tissue
• circadian clock
• development
• TGF-β
• pathway

This article refers to:

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Funding

This work was supported by American Heart Association grant 12SDG12080076, American Diabetes Association grant 1-13-BS-118 to KM, and American Diabetes Association grant 7-12-BS-210 and National Institute of Health grant DK097160-01 to VY.