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BCATm KO mice have elevated branched chain amino acids (BCAAs), a propensity to be lean, and show improvements in endpoints associated with obesity co‐morbidities
Author(s) -
She Pengxiang,
Bronson Sarah,
Van Horn Cynthia,
Reid Tanya,
Lynch Christopher,
Hutson Susan M.
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.21.5.a163-a
Subject(s) - medicine , endocrinology , obesity , weight loss , lean body mass , chemistry , fat mass , adipocyte , biology , body weight , adipose tissue
Increasing dietary protein has been linked to beneficial effects on insulin sensitivity, lean body mass and obesity. Leu or BCAAs have been implicated as the active agents. To address the role of BCAAs in obesity, we used the Crelox system to generate knock out (KO) mice lacking the mitochondrial isoform of branched‐chain aminotransferase (BCATm), which catalyzes the first step in BCAA metabolism. KOs had elevated plasma concentrations even when allowed to choose between BCAA‐free and –containing diets (choice diet). Differences in body weight on the choice diet could be seen after the 7 th week of age. After 18 weeks, male KOs exhibited a 10–15% lower body weight, associated with decreased epididymal fat pad mass (~60% loss), decreased adipocyte diameter and generally‐elevated caloric intake (body weight‐adjusted). Rates of oxygen consumption were increased by 32% during the light and dark cycle in the KO mice, suggesting increased energy expenditure. RQs were also increased, suggesting increased reliance on carbohydrate as fuel. Indeed, KOs had lower fasting plasma glucose and insulin as well as large decreases in areas under curve during GTTs and ITTs. Other obesity relevant endpoints were also improved and the animals were robustly resistant to diet‐induced obesity. These findings suggest that BCATm might be a relevant peripheral target for obesity therapy. DK053843 (CJL), DK062880 (CJL/SMH), DK34738 (SMH)