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Baylor College of Medicine News

Master regulator SRC-2 controls fat absorption

When cells run out of energy, a biological "rheostat" involving a molecule called SRC-2 resets energy available on a whole-body basis by promoting the absorption of fat in the gut, said researchers from Baylor College of Medicine in a report that appears in the current issue of the journal Cell Metabolism.

That rheostat's action begins with an enzyme called AMPK that senses when energy is depleted and activates SRC-2 (steroid receptor 2), a master regulator for energy, said Dr. Bert O'Malley, chair of molecular and cellular biology at BCM and the report's senior author.

Fat as a source of energy

"It's a system that developed over years of evolution," said O'Malley. "This controls the absorption of energy or fat through the intestine."

While that ability to use fat as an energy source promoted survival in periods when food was scarce, a major problem today is obesity, the rates of which have doubled among adults in the United States over the past 30 years. The rates in children for the same period have tripled.

Possible key to addressing obesity

O'Malley and his colleagues hypothesize that SRC-2 may serve as a potential target to fine tune levels of stored energy or fat in the body and thus combat the worldwide obesity epidemic.

"Overall, SRC-2 is a master regulator of energy accretion and storage," said O'Malley, who has studied the family of steroid receptor coactivators over the past 20 years.

Studies of mice that lack SRC-2 show they eat the same amount of food as mice that have the molecule, but they excrete greater amounts of fecal material that included high levels of fats. The levels of fats called triglycerides circulating in their bloodstreams decrease when SRC-2 is absent.

This indicates that the lack of SRC-2 reduced the animals' ability to absorb fat from the gut, said O'Malley and his colleagues in the report. The same patterns were seen in animals that lacked SRC-2 only in the liver, indicating that the SRC-2 works in the liver to promote fat absorption.

"Our results have implicated the SRC-2 coactivator as a newly discovered, essential cog in the AMPK-mediated energy regeneration wheel," the authors wrote. "We have elucidated a pathway that links cellular energy depletion with the act of priming the entry of dietary fuel into the body, thereby linking the cellular energy state with the whole-animal energy state."

Energy regeneration cycle

The cycle begins when supplies of energy in the form of ATP (adenosine triphosphate) drop in the cells, probably between meals. This activates AMPK and SRC-2, which allows the liver to secrete bile acids into the gall bladder and primes the gut to absorb fats in the form of triglycerides from the next meal. This becomes fuel for oxidation of fatty acids, which results in the formation of ATP.

Others who took part in this research include Atul R. Chopra, Ramakrishna Kommagani, Pradip Saha, Jean-Francois Louet,Christina Salazar, Junghun Song, Jaewook Jeong, Milton Finegold, Franco DeMayo, Lawrence Chan and David D. Moore, all of BCM, and Benoit Viollet Institut Cochin, Université Paris Descartes in Paris, France.

Funding for this work came from the National Institute of Diabetes and Digestive and Kidney Diseases and the Welch Foundation.