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

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

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

Bibliographical note

Funding Information:
National Institute of Diabetes and Digestive and Kidney Diseases R00DK094973 Teppei Fujikawa. American Heart Association 14SDG17950008 Carlos M Castorena National Research Foundation of Korea NRF-2013R1A1A1007693 Ki Woo Kim. Cancer Prevention and Research Institute of Texas RP110486P3 Joseph A Hill. Fondation Leducq 11CVD04 Joseph A Hill. National Heart, Lung, and Blood Institute HL-120732 Joseph A Hill. National Institute of Diabetes and Digestive and Kidney Diseases R01 DK100659 Joseph A Hill. National Institute of Diabetes and Digestive and Kidney Diseases P01 DK088761 Joseph A Hill. American Heart Association 14SFRN20740000 Philipp E Scherer, Joel K Elmquist. National Heart, Lung, and Blood Institute HL-100401 William L Holland. National Institute of Diabetes and Digestive and Kidney Diseases F32 DK104659 Joel K Elmquist. National Institute of Diabetes and Digestive and Kidney Diseases DK100659 Joel K Elmquist. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Publisher Copyright:
© 2016 Fujikawa et al.

All Science Journal Classification (ASJC) codes

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

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