Editors' ChoiceObesity

Rhythm fuels the adipose tissue fire

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Science Translational Medicine  06 Apr 2016:
Vol. 8, Issue 333, pp. 333ec56
DOI: 10.1126/scitranslmed.aaf6934

The expansion of adipose tissue in obese individuals is closely associated with the development of a number of chronic diseases, including diabetes, cardiovascular disease, and certain types of cancer. Thus, there is a clear unmet need for effective obesity therapies. Recent studies have deciphered distinct types of adipose tissues (white, brown, and beige) that differentially affect energy homeostasis. Such discoveries about human physiology have the potential to pinpoint new therapeutic targets. In this vein, Lee et al. demonstrate an underappreciated circadian rhythm associated with the glucose-fueled activity of brown adipose tissue (BAT).

Classic white adipose tissue functions primarily as a depot to store energy, whereas brown adipose tissue (BAT) and the recently described beige adipose tissue function to burn energy and generate heat through a process called nonshivering thermogenesis. It has long been assumed that adult humans do not have enough measurable thermogenic brown or beige adipose tissue to have an impact on energy expenditure, and this assumption has dampened enthusiasm for drug discovery in this area. However, a recent series of high-profile papers that demonstrate the existence of BAT in adult humans has sparked a revival in the field. Although there are still many detractors, the prevailing hypothesis is that therapeutic strategies that convert classic white adipose tissue into beige or brown adipose tissue could be effective in the treatment of obesity-related disorders.

Brown adipose tissue is typically thought to protect the body from cold temperatures via its key role in nonshivering thermogenesis. As a surrogate for BAT-driven thermogenesis, the authors measured supraclavical skin temperature in human subjects under both cold-stressed (14o to 18oC) and thermoneutral (24oC) conditions. Skin temperature correlated with 18F-deoxyglucse (FDG)–positron emission tomography measurements in human BAT. The authors also demonstrated that human BAT activity increased during an oral glucose tolerance test and provided evidence that BAT can use glucose as a thermogenic fuel. By following supraclavical skin temperature over a 12-hour period in subjects stratified for low and high BAT activity, the author uncovered a circadian-like rhythmicity associated with BAT glucose utilization. This circadian rhythm of glucose metabolism was maintained in cultured human brown adipocytes, indicating that a cell-autonomous clock exists to regulate delivery of glucose to thermogenic brown adipocytes. These findings have uncovered a previously underappreciated role for BAT in controlling systemic circadian and meal-related fluctuations in glycemia. It is likely that strategies for stimulating BAT-driven thermogenesis hold promise for the discovery and development of obesity therapeutics, but additional research is required to understand how this circadian circuit aligns with the well-documented ability of BAT to consume fatty acids for thermogenic fuel. Although it was long assumed that BAT-driven thermogenesis was relevant only in rodents, new findings in human subjects and isolated tissues now stoke the fire for research on BAT-targeted therapeutics.

P. Lee et al., Brown adipose tissue exhibits a glucose-responsive thermogenic biorhythm in humans. Cell Metab. 10.1016/j.cmet.2016.02.007 (2016). [Abstract]

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