Abstract
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.
Highlights
Steroidogenic factor 1 (SF-1) is a nuclear receptor expressed in the adrenal glands, gonads, anterior pituitary, and ventromedial nucleus of the hypothalamus (VMH) [1]
These results indicate that steroidogenic factor 1 (SF-1) is required for the regulation of normal energy balance in the aging process
The central nervous system (CNS) regulates energy homeostasis by integrating and responding to nutritional signals generated by the peripheral organs such as the circulating insulin and leptin levels
Summary
Steroidogenic factor 1 (SF-1) is a nuclear receptor expressed in the adrenal glands, gonads, anterior pituitary, and ventromedial nucleus of the hypothalamus (VMH) [1]. SF-1 is vital for the development of the VMH and for its physiological functions [2, 3]. The VMH is an important hypothalamic nucleus critical for regulating feeding and maintaining whole body energy homeostasis. Lesions in the VMH alter feeding behavior and have been associated with hyperphagia and development of obesity [4]. The VMH functions as a nutrient sensor and has been shown to respond to declining nutritional conditions such as hypoglycemia by inhibiting insulin production and stimulating glucagon and catecholamines release [5]. The expression of leptin receptors in the VMH depicts the importance
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