PGC-1α is required for exercise- and exercise training-induced UCP1 up-regulation in mouse white adipose tissue

PLoS One. 2013 May 22;8(5):e64123. doi: 10.1371/journal.pone.0064123. Print 2013.

Abstract

Background: The aim of the present study was to test the hypotheses that 1) a single exercise bout increases UCP1 mRNA in both inguinal (i)WAT and epididymal (e)WAT, 2) UCP1 expression and responsiveness to exercise are different in iWAT and eWAT, 3) PGC-1α determines the basal levels of UCP1 and PRDM16 in WAT and 4) exercise and exercise training regulate UCP1 and PRDM16 expression in WAT in a PGC-1α-dependent manner.

Methods: Whole body PGC-1α knockout (KO) and wildtype (WT) littermate mice performed a single treadmill exercise bout at 14 m/min and 10% slope for 1 hour. Mice were sacrificed and iWAT, eWAT and quadriceps muscle were removed immediately after, 2, 6 and 10 hours after running, and from sedentary mice that served as controls. In addition, PGC-1α KO mice and WT littermates were exercise trained for 5 weeks with sedentary mice as untrained controls. Thirty-six-37 hours after the last exercise bout iWAT was removed.

Results: UCP1 mRNA content increased 19-fold in iWAT and 7.5-fold in eWAT peaking at 6 h and 0' of recovery, respectively, in WT but with no changes in PGC-1α KO mice. UCP1 protein was undetectable in eWAT and very low in iWAT of untrained mice but increased with exercise training to 4.4 (AU) in iWAT from WT mice without significant effects in PGC-1α KO mice.

Conclusion: The present observations provide evidence that exercise training increases UCP1 protein in iWAT through PGC-1α, likely as a cumulative effect of transient increases in UCP1 expression after each exercise bout. Moreover, the results suggest that iWAT is more responsive than eWAT in exercise-induced regulation of UCP1. In addition, as PRDM16 mRNA content decreased in recovery from acute exercise, the present findings suggest that acute exercise elicits regulation of several brown adipose tissue genes in mouse WAT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / metabolism*
  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Glycogen / genetics
  • Glycogen / metabolism
  • Ion Channels / genetics*
  • Ion Channels / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Physical Conditioning, Animal
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Quadriceps Muscle / metabolism
  • RNA, Messenger / genetics
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Uncoupling Protein 1
  • Up-Regulation / genetics*

Substances

  • DNA-Binding Proteins
  • Ion Channels
  • Mitochondrial Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Ppargc1a protein, mouse
  • Prdm16 protein, mouse
  • RNA, Messenger
  • Transcription Factors
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Glycogen

Grants and funding

The study was supported by the Lundbeck Foundation. The Centre of Inflammation and Metabolism (CIM) is supported by a grant from the Danish National Research Foundation (# 02-512-55). CIM is part of the UNIK Project: Food, Fitness & Pharma for Health and Disease, supported by the Danish Ministry of Science, Technology, and Innovation. CIM is a member of DD2 - the Danish Center for Strategic Research in Type 2 Diabetes (the Danish Council for Strategic Research, grant no. 09-067009 and 09-075724). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.