SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise

Teppei Fujikawa, Carlos M. Castorena, Mackenzie Pearson, Christine M. Kusminski, Newaz Ahmed, Pavan K. Battiprolu, Ki Woo Kim, Syann Lee, Joseph A. Hill, Philipp E. Scherer, William L. Holland, Joel K. Elmquist

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Abstract

Exercise has numerous beneficial metabolic effects. The central nervous system (CNS) is critical for regulating energy balance and coordinating whole body metabolism. However, a role for the CNS in the regulation of metabolism in the context of the exercise remains less clear. Here, using genetically engineered mice we assessed the requirement of steroidogenic factor-1 (SF-1) expression in neurons of the ventromedial hypothalamic nucleus (VMH) in mediating the beneficial effects of exercise on metabolism. We found that VMH-specific deletion of SF-1 blunts (a) the reductions in fat mass, (b) improvements in glycemia, and (c) increases in energy expenditure that are associated with exercise training. Unexpectedly, we found that SF-1 deletion in the VMH attenuates metabolic responses of skeletal muscle to exercise, including induction of PGC-1a expression. Collectively, this evidence suggests that SF-1 expression in VMH neurons is required for the beneficial effects of exercise on metabolism.

Original languageEnglish
Article numbere18206
JournaleLife
Volume5
Issue numberNOVEMBER2016
DOIs
Publication statusPublished - 2016 Nov 22

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Fujikawa, T., Castorena, C. M., Pearson, M., Kusminski, C. M., Ahmed, N., Battiprolu, P. K., Kim, K. W., Lee, S., Hill, J. A., Scherer, P. E., Holland, W. L., & Elmquist, J. K. (2016). SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise. eLife, 5(NOVEMBER2016), [e18206]. https://doi.org/10.7554/eLife.18206