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

doi:10.7554/eLife.18206

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

Department of Oral Biology

Research output: Contribution to journal › Article › peer-review

28 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 language	English
Article number	e18206
Journal	eLife
Volume	5
Issue number	NOVEMBER2016
DOIs	https://doi.org/10.7554/eLife.18206
Publication status	Published - 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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10.7554/eLife.18206

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title = "SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise",

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.",

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

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: {\textcopyright} 2016 Fujikawa et al.",

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doi = "10.7554/eLife.18206",

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AU - Castorena, Carlos M.

AU - Pearson, Mackenzie

AU - Kusminski, Christine M.

AU - Ahmed, Newaz

AU - Battiprolu, Pavan K.

AU - Kim, Ki Woo

AU - Lee, Syann

AU - Hill, Joseph A.

AU - Scherer, Philipp E.

AU - Holland, William L.

AU - Elmquist, Joel K.

N1 - 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.

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Y1 - 2016/11/22

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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