Hypothalamic control of energy expenditure and thermogenesis

Abstract

Energy expenditure and energy intake need to be balanced to maintain proper energy homeostasis. Energy homeostasis is tightly regulated by the central nervous system, and the hypothalamus is the primary center for the regulation of energy balance. The hypothalamus exerts its effect through both humoral and neuronal mechanisms, and each hypothalamic area has a distinct role in the regulation of energy expenditure. Recent studies have advanced the understanding of the molecular regulation of energy expenditure and thermogenesis in the hypothalamus with targeted manipulation techniques of the mouse genome and neuronal function. In this review, we elucidate recent progress in understanding the mechanism of how the hypothalamus affects basal metabolism, modulates physical activity, and adapts to environmental temperature and food intake changes.

Fig. 1. Schematic summary of the hypothalamic nuclei involved in the regulation of physical activity.

Different neuronal populations and nuclei have different effectors and mechanisms to promote physical activities in the form of spontaneous physical activity or exercise, resulting in an increase in energy expenditure. Dashed lines: putative or unclear pathways or effects. Arrowheads: inducing or projecting. Blunted-bar heads: inhibiting. AgRP, agouti-related peptide; ARC, arcuate nucleus of the hypothalamus; BDNF, brain-derived neurotrophic factor; DMH, dorsomedial hypothalamus; GABA, gamma-aminobutyric acid; LepR, leptin receptor long form; LH, lateral hypothalamus; POMC, proopiomelanocortin; PVN, paraventricular hypothalamus; SF-1, steroidogenic factor 1; TrkB, tropomyosin receptor kinase B; VMH, ventromedial hypothalamus.

Fig. 2. Schematic summary of the hypothalamic nuclei involved in the regulation of thermogenesis.

Adaptive thermogenesis from nutritional or hormonal cues or from ambient temperature changes is controlled through different hypothalamic pathways. UCP1-dependent thermogenesis causes an increase in UCP1 expression in brown adipose tissue and “beiging” in white adipose tissue, thus increasing heat production. Arrowheads: inducing or projecting, Blunted-bar heads: inhibiting. 3V, third ventricle; αMSH, alpha-melanocyte-stimulating hormone; AgRP, agouti-related peptide; ARC, arcuate nucleus of the hypothalamus; β-AR, beta-adrenergic receptor; BAT, brown adipose tissue; ERα, estrogen receptor alpha; POMC, proopiomelanocortin; PVN, paraventricular hypothalamus; SF-1, steroidogenic factor; VMH, ventromedial hypothalamus; WAT, white adipose tissue.