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Evidence of a novel mechanism of increased energy expenditure in the BCATm KO mouse
Author(s) -
She Pengxiang,
Vary Thomas C,
Bronson Sarah K.,
Carrel Laura,
Hutson Susan M,
Lynch Christopher J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a837-d
Subject(s) - medicine , endocrinology , catabolism , protein turnover , adipose tissue , protein catabolism , thermogenesis , chemistry , skeletal muscle , energy expenditure , brown adipose tissue , metabolism , biology , protein biosynthesis , amino acid , biochemistry
The mechanism underlying increased energy expenditure in BCATm KO mice was investigated. BCATm KOs have elevated food intake normalized to body weight, but reduced adipose tissue mass and cell size associated with increased rates of oxygen consumption (VO 2 ) during the light and dark cycle (~32%), suggesting increased energy expenditure. Factors frequently associated with altered VO 2 in mice, were not affected in the KO. These included: plasma T4; relevant tissue expression of iodothyronine deiodinase‐2 (D2), UCP‐1, PGC‐1α, β‐adrenergic receptor 3, SERCA1 and glycerol phosphate dehydrogenase; Locomotive activity. Fasting‐re‐feeding studies suggested that the increased VO 2 is linked to food intake. After lowering BCAAs, by dietary manipulation, food intake and energy expenditure increased further and became highly correlated. Surprisingly, fed protein synthesis rates in the KO were increased by 33–83% in heart, skeletal muscle, fat, and kidney, without a corresponding effect on protein accretion. Urinary 3‐MeHis were elevated and fibroblasts prepared from newborn KOs had increased rates of protein degradation in pulse chase studies. Thus, the loss of BCAA catabolism results in increased protein degradation, accompanied by increased feeding‐associated protein synthesis. Our results suggest a role for a protein‐amino acid futile cycle in the increased energy expenditure. DK053843 DK062880