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

Pengxiang She, Tanya M. Reid, Sarah K. Bronson, Thomas C. Vary, Andras Hajnal, Christopher J. Lynch, Susan M. Hutson

Research output: Contribution to journalArticle

221 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)181-194
Number of pages14
JournalCell Metabolism
Volume6
Issue number3
DOIs
StatePublished - Sep 5 2007

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Branched Chain Amino Acids
Energy Metabolism
Leucine
Food
Proteins
Adiposity
Locomotion
Thyroid Hormones
Proteolysis
Insulin Resistance
Obesity
Eating
Body Weight
Insulin
Diet
Glucose
Enzymes
Genes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

She, Pengxiang ; Reid, Tanya M. ; Bronson, Sarah K. ; Vary, Thomas C. ; Hajnal, Andras ; Lynch, Christopher J. ; Hutson, Susan M. / Disruption of BCATm in Mice Leads to Increased Energy Expenditure Associated with the Activation of a Futile Protein Turnover Cycle. In: Cell Metabolism. 2007 ; Vol. 6, No. 3. pp. 181-194.
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Disruption of BCATm in Mice Leads to Increased Energy Expenditure Associated with the Activation of a Futile Protein Turnover Cycle. / She, Pengxiang; Reid, Tanya M.; Bronson, Sarah K.; Vary, Thomas C.; Hajnal, Andras; Lynch, Christopher J.; Hutson, Susan M.

In: Cell Metabolism, Vol. 6, No. 3, 05.09.2007, p. 181-194.

Research output: Contribution to journalArticle

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