NT-PGC-1α activation attenuates high-fat diet-induced obesity by enhancing brown fat thermogenesis and adipose tissue oxidative metabolism

  1. Ji Suk Chang
  1. From the Laboratory of Nutrient Sensing and Adipocyte Signaling,
  2. 1From the Laboratory of Skeletal Muscle Metabolism, Pennington Biomedical Research Center, Baton Rouge, LA 70808
  1. Corresponding authors: Ji Suk Chang, E-mail: jisuk.chang{at}pbrc.edu

Abstract

The transcriptional coactivator PGC-1α and its splice variant NT-PGC-1α regulate adaptive thermogenesis by transcriptional induction of thermogenic and mitochondrial genes involved in energy metabolism. We previously reported that full-length PGC-1α (FL-PGC-1α) is dispensable for cold-induced nonshivering thermogenesis in FL-PGC-1α-/- mice since a slightly shorter but functionally equivalent form of NT-PGC-1α (NT-PGC-1α254) fully compensates for the loss of full-length PGC-1α in brown and white adipose tissue. In the present study, we challenged FL-PGC-1α-/- mice with a high-fat diet (HFD) to investigate the effects of diet-induced thermogenesis on HFD-induced obesity. Despite a large decrease in locomotor activity, FL-PGC-1α-/- mice exhibited the surprising ability to attenuate HFD-induced obesity. Reduced fat mass in FL-PGC-1α-/- mice was closely associated with an increase in body temperature, energy expenditure, and whole body fatty acid oxidation (FAO). Mechanistically, FL-PGC-1α-/- brown adipose tissue had an increased capacity to oxidize fatty acids and dissipate energy as heat, in accordance with upregulation of thermogenic genes UCP1 and DIO2. Furthermore, augmented expression of FAO and lipolytic genes in FL-PGC-1α-/- white adipose tissue was highly correlated with decreased fat storage in adipose tissue. Collectively, our data highlight a protective effect of NT-PGC-1α on diet-induced obesity by enhancing diet-induced thermogenesis and fatty acid oxidation.

  • Received December 3, 2013.
  • Accepted May 15, 2014.

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