Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus Regulates Age-Dependent Obesity.
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.
Departments of Pharmacology and Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea.
Ann W
AW
Kinyua
Departments of Pharmacology and Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea.
Dong Joo
DJ
Yang
Department of Oral Biology, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea.
Inik
I
Chang
Departments of Pharmacology and Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea.|Division of Hypothalamic Research, Department of Internal Medicine and Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX, 75390, United States of America.
Ki Woo
KW
Kim
D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000473:pathology; D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating / Q000235:genetics; D004734:Energy Metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D007328:Insulin / Q000097:blood / Q000235:genetics*; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D010101:Oxygen Consumption / Q000502:physiology; D015398:Signal Transduction; D054339:Steroidogenic Factor 1 / Q000172:deficiency / Q000235:genetics*; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism* / Q000503:physiopathology
D001786:Blood Glucose; D051273:Glucose Transporter Type 2; D007328:Insulin; D020738:Leptin; C495682:Slc2a2 protein, mouse; D054339:Steroidogenic Factor 1; C515058:steroidogenic factor 1, mouse