Disruption of BCATm in Mice Leads to Increased Energy Expenditure Associated with the Activation of a Futile Protein Turnover Cycle

Leucine is recognized as a nutrient signal; however, the long-term in vivo consequences of leucine signaling and the role of branched-chain amino acid (BCAA) metabolism in this signaling remain unclear. To investigate these questions, we disrupted the BCATm gene, which encodes the enzyme catalyzing...

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Bibliographic Details
Published in:Cell metabolism 2007-09, Vol.6 (3), p.181-194
Main Authors: She, Pengxiang, Reid, Tanya M., Bronson, Sarah K., Vary, Thomas C., Hajnal, Andras, Lynch, Christopher J., Hutson, Susan M.
Format: Article
Language:English
Subjects:
Adipose Tissue - cytology
Adipose Tissue - metabolism
Animals
Body Weight
Diet
Eating
Energy Metabolism
Female
Gene Targeting
Glucose Tolerance Test
Humans
HUMDISEASE
Insulin - metabolism
Leucine - metabolism
Male
Mice
Mice, Knockout
Obesity - metabolism
Obesity - prevention & control
Organ Size
Oxygen Consumption
Protein Kinases - metabolism
PROTEINS
Proteins - metabolism
Sirolimus - metabolism
Substrate Cycling
Thermogenesis - physiology
TOR Serine-Threonine Kinases
Transaminases - genetics
Transaminases - metabolism
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Summary:Leucine is recognized as a nutrient signal; however, the long-term in vivo consequences of leucine signaling and the role of branched-chain amino acid (BCAA) metabolism in this signaling remain unclear. To investigate these questions, we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism. BCATm−/− mice exhibited elevated plasma BCAAs and decreased adiposity and body weight, despite eating more food, along with increased energy expenditure, remarkable improvements in glucose and insulin tolerance, and protection from diet-induced obesity. The increased energy expenditure did not seem to be due to altered locomotor activity, uncoupling proteins, sympathetic activity, or thyroid hormones but was strongly associated with food consumption and an active futile cycle of increased protein degradation and synthesis. These observations suggest that elevated BCAAs and/or loss of BCAA catabolism in peripheral tissues play an important role in regulating insulin sensitivity and energy expenditure.
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2007.08.003