Increased energy expenditure and insulin sensitivity in the high bone mass DeltaFosB transgenic mice

Endocrinology. 2009 Jan;150(1):135-43. doi: 10.1210/en.2008-0678. Epub 2008 Sep 4.

Abstract

Obesity and osteoporosis are major health issues affecting millions of individuals. Transgenic mice overexpressing DeltaFosB, an activator protein-1 transcription factor, under the control of the enolase 2 (ENO2) promoter exhibit both an increase in bone density and a decrease in adipose mass. Here we demonstrate that DeltaFosB overexpression increases fatty-acid oxidation and energy expenditure, leading to a decrease in adipocyte size and adipose mass. In addition, the ENO2-DeltaFosB mice exhibit increased insulin sensitivity and glucose tolerance. Targeted overexpression of DeltaFosB in adipocytes using the adipocyte protein 2 promoter failed to induce changes in fat or in bone, showing that the effect on metabolic activity is not due to cell-autonomous effects of DeltaFosB within adipocytes. Detailed analysis of the ENO2-DeltaFosB mice demonstrated that energy expenditure was increased in muscle, independent of locomotor activity. These findings provide evidence that signaling downstream of DeltaFosB is a potential target for not only osteoporosis but also obesity and diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density / genetics*
  • Energy Intake
  • Energy Metabolism / drug effects*
  • Fatty Acids / metabolism
  • Insulin / pharmacology*
  • Mice
  • Mice, Transgenic*
  • Obesity / genetics
  • Organ Size / genetics
  • Osteocalcin / metabolism
  • Phosphopyruvate Hydratase / genetics
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-fos / deficiency
  • Proto-Oncogene Proteins c-fos / genetics*

Substances

  • Fatty Acids
  • Fosb protein, mouse
  • Insulin
  • Proto-Oncogene Proteins c-fos
  • Osteocalcin
  • Phosphopyruvate Hydratase