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Darkness unveils vital metabolic fuel switch between sugar and fat

Constant darkness throws a molecular switch in mammals that shifts the body's fuel consumption from glucose to fat and induces a state of torpor in mice, a research team led by scientists at The University of Texas Medical School at Houston reports in the Jan. 19 edition of Nature.

While their findings could provide new insight into mammalian hibernation, researchers note that the pivotal metabolic signal that emerged from the dark also presents a new target for obesity and type 2 diabetes research. A series of experiments pinpointed 5-prime adenosine monophosphate (5'-AMP) as the key molecular mediator of the constant darkness effect, switching mice from a glucose-burning, fat-storing state to a fat-burning, glucose-conserving lethargy.

Active mammals ?a bear foraging for food or a human running a marathon ?also undergo a similar switch, burning glucose first to fuel their efforts, and as blood sugar is consumed, their bodies switch to burning fat.

"How does the body know when to switch? 5'-AMP is the signal. I believe it's the same metabolic system, whether we are talking about hibernation or not," said senior author Cheng Chi Lee, Ph.D., professor of biochemistry.

The team started with a basic question: What actually sets off hibernation? "These animals dig deep burrows," said Lee, an expert in circadian rhythms. "They are constantly in the dark. Why not darkness as a switch?"

Mice do not hibernate but they can slip into a similar short-term state of torpor. Lee and colleagues started with a microarray analysis of gene expression in the livers of mice subject to the usual light-dark cycle and those kept in the dark for 48 hours.

One gene fired up in the dark ?procolipase, which produces an enzyme (CLPS) required for degrading dietary fat. Expression of the gene previously was thought to be restricted to the pancreas and gastrointestinal tract. Yet messenger RNA for CLPS (mClps) was found in the liver
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Source:University of Texas Health Science Center at Houston


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