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

GC Rowe, CS Choi, L Neff, WC Horne… - …, 2009 - academic.oup.com
GC Rowe, CS Choi, L Neff, WC Horne, GI Shulman, R Baron
Endocrinology, 2009academic.oup.com
Obesity and osteoporosis are major health issues affecting millions of individuals.
Transgenic mice overexpressing ΔFosB, 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 ΔFosB overexpression increases fatty-
acid oxidation and energy expenditure, leading to a decrease in adipocyte size and adipose
mass. In addition, the ENO2-ΔFosB mice exhibit increased insulin sensitivity and glucose …
Obesity and osteoporosis are major health issues affecting millions of individuals. Transgenic mice overexpressing ΔFosB, 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 ΔFosB overexpression increases fatty-acid oxidation and energy expenditure, leading to a decrease in adipocyte size and adipose mass. In addition, the ENO2-ΔFosB mice exhibit increased insulin sensitivity and glucose tolerance. Targeted overexpression of ΔFosB 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 ΔFosB within adipocytes. Detailed analysis of the ENO2-ΔFosB mice demonstrated that energy expenditure was increased in muscle, independent of locomotor activity. These findings provide evidence that signaling downstream of ΔFosB is a potential target for not only osteoporosis but also obesity and diabetes.
Overexpression of ΔFosB under the control of the enolase 2 promoter increases bone mass and energy expenditure by increasing fatty-acid oxidation within muscle, reducing adiposity.
Oxford University Press