title: Increased energy expenditure and insulin sensitivity in the high bone mass DeltaFosB transgenic mice.
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.
authors.affiliation: Department of Orthopaedics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Rowe
authors.forename: Cheol Soo
authors.initials: CS
authors.lastname: Choi
authors.forename: Lynn
authors.initials: L
authors.lastname: Neff
authors.forename: William C
authors.initials: WC
authors.lastname: Horne
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
authors.forename: Roland
authors.initials: R
authors.lastname: Baron
mesh_terms: 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*
chemical_list: D005227:Fatty Acids; C483819:Fosb protein, mouse; D007328:Insulin; D016760:Proto-Oncogene Proteins c-fos; D015675:Osteocalcin; D010751:Phosphopyruvate Hydratase
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