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Insulin Resistance Linked to Fat and Amino Acid Breakdown

Resistance observed only with a high-fat diet

WEDNESDAY, April 8 (HealthDay News) -- Obese individuals differ from lean individuals in the breakdown of certain amino acids, which can lead to insulin resistance in the context of a high-fat diet, researchers report in the April 8 issue of Cell Metabolism.

Christopher B. Newgard, Ph.D., and colleagues from Duke University Medical Center in Durham, N.C., measured hormones, cytokines and metabolites in 74 "healthy" obese individuals (free of serious illnesses) and 67 lean individuals.

The investigators found a metabolic "signature" in obese subjects associated with the catabolism of branched-chain amino acids (BCAA). Rats fed a high-fat diet supplemented with BCAA were as insulin-resistant as rats fed a high-fat diet, despite the fact that they had reduced food intake and weight gain. Supplementing standard rat chow with BCAA did not lead to insulin resistance, the researchers note. Insulin resistance resulting from a high-fat diet and BCAA supplementation was associated with changes in cellular signaling, which could be reversed by rapamycin, an immunosuppressant.

"Our findings show that in the context of a dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance," Newgard and colleagues conclude.

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