Elevated mitochondrial biogenesis in skeletal muscle is associated with testosterone-induced body weight loss in male mice

FEBS Lett. 2014 May 21;588(10):1935-41. doi: 10.1016/j.febslet.2014.03.051. Epub 2014 Apr 12.

Abstract

Androgen reduces fat mass, although the underlying mechanisms are unknown. Here, we examined the effect of testosterone on heat production and mitochondrial biogenesis. Testosterone-treated mice exhibited elevated heat production. Treatment with testosterone increased the expression level of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), ATP5B and Cox4 in skeletal muscle, but not that in brown adipose tissue and liver. mRNA levels of genes involved in mitochondrial biogenesis were elevated in skeletal muscle isolated from testosterone-treated male mice, but were down-regulated in androgen receptor deficient mice. These results demonstrated that the testosterone-induced increase in energy expenditure is derived from elevated mitochondrial biogenesis in skeletal muscle.

Keywords: Androgen receptor deficient mice; Mitochondrial biogenesis; Skeletal muscle; Testosterone.

MeSH terms

  • Androgens / metabolism
  • Androgens / pharmacology
  • Animals
  • Blood Glucose / metabolism
  • Blotting, Western
  • Body Weight / drug effects*
  • Cell Line
  • Cytochromes c / genetics
  • Cytochromes c / metabolism
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Eating / drug effects
  • Energy Metabolism / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria, Muscle / genetics
  • Mitochondria, Muscle / metabolism*
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism*
  • Myoglobin / genetics
  • Myoglobin / metabolism
  • Nuclear Respiratory Factor 1 / genetics
  • Nuclear Respiratory Factor 1 / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Receptors, Androgen / deficiency
  • Receptors, Androgen / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Testosterone / metabolism
  • Testosterone / pharmacology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Troponin / genetics
  • Troponin / metabolism
  • Weight Loss / drug effects*

Substances

  • Androgens
  • Blood Glucose
  • DNA, Mitochondrial
  • Myoglobin
  • Nrf1 protein, mouse
  • Nuclear Respiratory Factor 1
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Receptors, Androgen
  • Transcription Factors
  • Troponin
  • Testosterone
  • Cytochromes c