Lack of energy-regulating gene caused mice to become obese and insulin resistant

Lack of energy-regulating gene caused mice to become obese and insulin resistant

A team of scientists in the US found that mice lacking a gene that is involved with and controls enzymes that regulate energy production in cells became obese and insulin resistant even though they ate less and exercised more than their brothers and sisters.

The findings are the result of a study by Dr Rob Lewis of the Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, and 26 other researchers from various centers in the US. It was published in the journal Cell Metabolism on 4 November.

Lewis told the press that the genetically modified mouse, which they bred to lack a protein called Kinase Suppressor of Ras 2 (KSR2), was interesting because while it ate less and was more active than its normal brothers and sisters, it got fat.

"It's not unlike the person who diets, but has trouble losing weight," he added.

For the study, Lewis and colleagues showed that in mice, KSR2 interacts with and controls AMPK, an enzyme that helps generate energy and prevents it being stored, and when KSR2 was missing, AMPK couldn't do its job properly, which Lewis suggests contributed to obesity in the adult mice.

Lewis said the data indicates that the mice without KSR2 were highly efficient at conserving energy, revealing an unexpected role for KSR2 in energy metabolism involving AMPK.

"The insulin resistance appears to be secondary to obesity and similar to what physicians observe in some obese humans," he added.

Lewis said there was no suggestion that KSR2 affects insulin resistance in humans, although a commonly prescribed diabetes drug is thought to active AMPK indirectly to promote glucose uptake.

He and his team are now looking in more detail at how KSR proteins affect metabolism in obesity, insulin action and cancer.

Lewis told the press that recent research shows that the way cancer cells change how they metabolize glucose is key to tumor development and survival.

"Our preliminary studies suggest that KSR2 and a related gene, KSR1, play a critical role in determining how some tumor cells metabolize glucose," he explained, suggesting that a better understanding of metabolism in cancer cells could open the door to new treatments.

"KSR2 Is an Essential Regulator of AMP Kinase, Energy Expenditure, and Insulin Sensitivity."

Diane L. Costanzo-Garvey, Paul T. Pfluger, Michele K. Dougherty, Jeffery L. Stock, Matthew Boehm, Oleg Chaika, Mario R. Fernandez, Kurt Fisher, Robert L. Kortum, Eun-Gyoung Hong et al.

Cell Metabolism, Volume 10, Issue 5, 366-378, 4 November 2009


Source: UNMC.

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