Yohei Tanada1, Tetsuo Shioi2, Takao Kato3, Akira Kawamoto1, Junji Okuda1, Takeshi Kimura1. 1. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. 2. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: tshioi@kuhp.kyoto-u.ac.jp. 3. Cardiovascular Center, Tazuke Kofukai Medical Research Institute, Kitano Hospital, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan.
Abstract
AIMS: Heart failure (HF) is associated with changes in energy metabolism of the heart, as well as in extra-cardiac organs such as the skeletal muscles. Cardiac cachexia is a common complication and is associated with poor prognosis. Branched-chain amino acids (BCAAs) reportedly improve sarcopenia and cancer cachexia. We tested the hypothesis that BCAA ameliorates HF with cardiac cachexia. MAIN METHODS: We used Dahl salt-sensitive (DS) rats fed a high-salt diet as a model of HF. DS rats fed a low-salt diet were used as a control. BCAA were administered in drinking water from 11weeks of age, when cardiac hypertrophy was established but the cardiac function was preserved. Survival and the cardiac function were monitored, and animals were sacrificed at 21weeks of age and analyzed. KEY FINDINGS: In HF rats, BCAA treatment decreased the heart rate, preserved the cardiac function, and prolonged survival. BCAA also prevented body weight loss, associated with preservation of the skeletal muscle weight. Moreover, gene expression related to mitochondrial biogenesis and function was increased with BCAA in skeletal muscles. SIGNIFICANCE: BCAA preserved the body weight and cardiac function and prolonged survival in HF rats. The expression of genes involved in mitochondrial biogenesis and function in skeletal muscles was increased by BCAA.
AIMS: Heart failure (HF) is associated with changes in energy metabolism of the heart, as well as in extra-cardiac organs such as the skeletal muscles. Cardiac cachexia is a common complication and is associated with poor prognosis. Branched-chain amino acids (BCAAs) reportedly improve sarcopenia and cancer cachexia. We tested the hypothesis that BCAA ameliorates HF with cardiac cachexia. MAIN METHODS: We used Dahl salt-sensitive (DS) rats fed a high-salt diet as a model of HF. DS rats fed a low-salt diet were used as a control. BCAA were administered in drinking water from 11weeks of age, when cardiac hypertrophy was established but the cardiac function was preserved. Survival and the cardiac function were monitored, and animals were sacrificed at 21weeks of age and analyzed. KEY FINDINGS: In HF rats, BCAA treatment decreased the heart rate, preserved the cardiac function, and prolonged survival. BCAA also prevented body weight loss, associated with preservation of the skeletal muscle weight. Moreover, gene expression related to mitochondrial biogenesis and function was increased with BCAA in skeletal muscles. SIGNIFICANCE: BCAA preserved the body weight and cardiac function and prolonged survival in HF rats. The expression of genes involved in mitochondrial biogenesis and function in skeletal muscles was increased by BCAA.
Authors: Haipeng Sun; Kristine C Olson; Chen Gao; Domenick A Prosdocimo; Meiyi Zhou; Zhihua Wang; Darwin Jeyaraj; Ji-Youn Youn; Shuxun Ren; Yunxia Liu; Christoph D Rau; Svati Shah; Olga Ilkayeva; Wen-Jun Gui; Noelle S William; R Max Wynn; Christopher B Newgard; Hua Cai; Xinshu Xiao; David T Chuang; Paul Christian Schulze; Christopher Lynch; Mukesh K Jain; Yibin Wang Journal: Circulation Date: 2016-04-08 Impact factor: 29.690