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Brown fat in adults follows circadian rhythm

A baby's brown fat is known to protect it from cold temperatures. Now research has discovered brown fat in some adults also follows our circadian rhythm and may offer protection from cold and from diabetes.

Circadian rhythms rise just before we wake and may have evolved as a thermal defense to help our early human ancestors hunt and gather in the cold morning hours. Brown fat consumes glucose — the fuel of heat production — and reflects the same morning rise in circadian rhythm.

The research appeared March 10 in Cell Metabolism.

"Day-to-day glucose variations may be a precursor to diabetes. For modern humans who do not rely on it for cold protection, energy-consuming brown fat rhythms may act as a buffer to smooth glucose fluctuations and lessen stress on the pancreas," says lead author Paul Lee PhD Medicine, a clinician scientist and endocrinologist at the Garvan Institute of Medical Research in Australia.

For survival, maintenance of body core temperature trumps need for food and water.

In response to cold temperatures, brown fat consumes large amounts of glucose and lipids as a fuel source to generate heat and keep the body warm.

By the same token, cold-induced activation of brown fat burns calories and lowers glucose levels, protecting animals against obesity and diabetes. But it has not been clear whether brown fat regulates glucose levels in the absence of cold exposure. While investigating this question, Lee and his team discovered that human brown fat cells show circadian fluctuations in glucose consumption.

Brown fat tissue samples were taken from surgical patients in order to study genes involved in their glucose uptake. The fat samples, surprisingly, showed rhythmic fluctuations rising during pre-waking sleep periods — a finding which may indicate brown fat helps regulate metabolic activity, above and beyond heat production.

Researchers also discovered that in the 15 healthy individuals with a high abundance of brown fat, there was less variability in their glucose levels over a 12-hour period when compared to individuals with little brown fat.

A hallmark of diabetes is a large fluctuation in glucose levels, which can increase risk for visual impairment, cardiovascular disease, kidney disease, and neurologic problems.

The authors urge caution about clinical implications as yet for their findings. "While interesting and promising, brown fat is not the solution to finding a cure for diabetes – at least not now," adds Lee. "A balanced diet and regular exercise are the cornerstones of healthy metabolism and should not be forgotten."

In future studies, the researchers plan to examine whether brown fat rhythm exists in people specifically with diabetes or other related metabolic disorders.

They will also investigate in greater detail how brown fat rhythms affect the control of metabolism.

"Pinpointing what switches on this brown fat rhythm may identify new targets for drug design and open new avenues to harness this glucose-responsive brown fat rhythm for potential therapeutic purposes."

Paul Lee PhD Medicine, Clinician Scientist and Endocrinologist, Garvan Institute of Medical Research, Australia.

Abstract Highlights
• Brown fat utilizes glucose as substrate fuel to produce heat in humans
• Human brown fat exhibits a thermogenic circadian rhythm
• Brown fat circadian rhythm is glucose responsive
• Low brown fat abundance is associated with greater glycaemic fluctuations

High abundance of brown adipose tissue (BAT) is linked to lower glycaemia in humans, leading to the belief that BAT may protect against diabetes. The relationship between BAT glucose utilization and systemic glucose homeostasis has not been defined. In this paper we have characterized glycaemic excursions and BAT thermogenic responses in human brown adipocytes, BAT explants, and healthy adults through supraclavicular temperature profiling, revealing their circadian coupling in vivo and in vitro, orchestrated by UCP1, GLUT4, and Rev-erbα biorhythms. Extent of glycated haemoglobin also correlated positively with environmental temperature among community-dwelling patients. These data uncover potential crosstalk between BAT and glucose regulatory pathways, evident on cellular, tissue, individual, and population levels, and provide impetus to search for BAT harnessing strategies for therapeutic purposes.

Cell Metabolism, Lee et al.: "Brown Adipose Tissue Exhibits a Glucose-Responsive Thermogenic Biorhythm in Humans" http://dx.doi.org/10.1016/j.cmet.2016.02.007

The authors were supported by the Australian National Health Medical Research Council, the Diabetes Australia Research Trust, and the Royal Australasian College of Physicians.

Cell Metabolism (@Cell_Metabolism), published by Cell Press, is a monthly journal that publishes reports of novel results in metabolic biology, from molecular and cellular biology to translational studies. The journal aims to highlight work addressing the molecular mechanisms underlying physiology and homeostasis in health and disease. Learn more at http://www.cell.com/cell-metabolism. To receive Cell Press media alerts, contact press@cell.com.

Related research:

Evidence Shivering and Exercise May Convert White Fat to Brown
A new study suggests that shivering and bouts of moderate exercise are equally capable of stimulating the conversion of energy-storing ‘white fat’ into energy-burning ‘brown fat’. This makes brown fat a potential therapeutic target against obesity and diabetes.

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Image Credit: Cell Metabolism




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