Increased energy expenditure and insulin sensitivity in the high bone mass DeltaFosB transgenic mice.
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.
Rowe
Glenn C
GC
Department of Orthopaedics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Choi
Cheol Soo
CS
Neff
Lynn
L
Horne
William C
WC
Shulman
Gerald I
GI
Baron
Roland
R
D000818:Animals; D015519:Bone Density / Q000235:genetics*; D002149:Energy Intake; D004734:Energy Metabolism / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics; D009929:Organ Size / Q000235:genetics; D015675:Osteocalcin / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D016133:Polymerase Chain Reaction; D016760:Proto-Oncogene Proteins c-fos / Q000172:deficiency / Q000235:genetics*
D005227:Fatty Acids; C483819:Fosb protein, mouse; D007328:Insulin; D016760:Proto-Oncogene Proteins c-fos; D015675:Osteocalcin; D010751:Phosphopyruvate Hydratase
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