The ventromedial nucleus of the hypothalamus (VMH) is important for the regulation of whole body energy homeostasis and lesions in the VMH are reported to result in massive weight gain. The nuclear receptor steroidogenic factor 1 (SF-1) is a known VMH marker as it is exclusively expressed in the VMH region of the brain. SF-1 plays a critical role not only in the development of VMH but also in its physiological functions. In this study, we generated prenatal VMH-specific SF-1 KO mice and investigated age-dependent energy homeostasis regulation by SF-1. Deletion of SF-1 in the VMH resulted in dysregulated insulin and leptin homeostasis and late onset obesity due to increased food intake under normal chow and high fat diet conditions. In addition, SF-1 ablation was accompanied by a marked reduction in energy expenditure and physical activity and this effect was significantly pronounced in the aged mice. Taken together, our data indicates that SF-1 is a key component in the VMH-mediated regulation of energy homeostasis and implies that SF-1 plays a protective role against metabolic stressors including aging and high fat diet.
Bibliographical noteFunding Information:
We would like to thank Dr. Yun-Hee Choi (Bio-FD & C, Co., LTD) for discussion during the manuscript preparation. This work was supported by Small and Medium Business Administration (Technological Innovation R&D Program S2178403), National Research Foundation (2016R1C1B3012748 and 2014K1A3A1A19066980 for K.W.K. and 2016R1A5A2008630 for I. C.), and Global PhD Fellowship (NRF-2015H1A2A1032009 for D. J. Y.).
© 2016 Kinyua et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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