Dietary branched-chain amino acid restriction alters fuel selection and reduces triglyceride stores in hearts of Zucker fatty rats.

Autor:	McGarrah RW; Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina.; Cardiology Division, Department of Medicine, Duke University Medical Center, Durham, North Carolina., Zhang GF; Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina.; Endocrinology Division, Department of Medicine, Duke University Medical Center, Durham, North Carolina., Christopher BA; Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina.; Cardiology Division, Department of Medicine, Duke University Medical Center, Durham, North Carolina., Deleye Y; Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina., Walejko JM; Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina., Page S; Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina., Ilkayeva O; Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina., White PJ; Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina.; Endocrinology Division, Department of Medicine, Duke University Medical Center, Durham, North Carolina.; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina., Newgard CB; Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina.; Endocrinology Division, Department of Medicine, Duke University Medical Center, Durham, North Carolina.; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2020 Feb 01; Vol. 318 (2), pp. E216-E223. Date of Electronic Publication: 2019 Dec 03.
DOI:	10.1152/ajpendo.00334.2019
Abstrakt:	Elevations in circulating levels of branched-chain amino acids (BCAAs) are associated with a variety of cardiometabolic diseases and conditions. Restriction of dietary BCAAs in rodent models of obesity lowers circulating BCAA levels and improves whole-animal and skeletal-muscle insulin sensitivity and lipid homeostasis, but the impact of BCAA supply on heart metabolism has not been studied. Here, we report that feeding a BCAA-restricted chow diet to Zucker fatty rats (ZFRs) causes a shift in cardiac fuel metabolism that favors fatty acid relative to glucose catabolism. This is illustrated by an increase in labeling of acetyl-CoA from [1- 13 C]palmitate and a decrease in labeling of acetyl-CoA and malonyl-CoA from [U- 13 C]glucose, accompanied by a decrease in cardiac hexokinase II and glucose transporter 4 protein levels. Metabolomic profiling of heart tissue supports these findings by demonstrating an increase in levels of a host of fatty-acid-derived metabolites in hearts from ZFRs and Zucker lean rats (ZLRs) fed the BCAA-restricted diet. In addition, the twofold increase in cardiac triglyceride stores in ZFRs compared with ZLRs fed on chow diet is eliminated in ZFRs fed on the BCAA-restricted diet. Finally, the enzymatic activity of branched-chain ketoacid dehydrogenase (BCKDH) is not influenced by BCAA restriction, and levels of BCAA in the heart instead reflect their levels in circulation. In summary, reducing BCAA supply in obesity improves cardiac metabolic health by a mechanism independent of alterations in BCKDH activity.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu