Neural Control of Energy Expenditure

Abstract

The continuous rise in obesity is a major concern for future healthcare management. Many strategies to control body weight focus on a permanent modification of food intake with limited success in the long term. Metabolism or energy expenditure is the other side of the coin for the regulation of body weight, and strategies to enhance energy expenditure are a current focus for obesity treatment, especially since the (re)-discovery of the energy depleting brown adipose tissue in adult humans. Conversely, several human illnesses like neurodegenerative diseases, cancer, or autoimmune deficiency syndrome suffer from increased energy expenditure and severe weight loss. Thus, strategies to modulate energy expenditure to target weight gain or loss would improve life expectancies and quality of life in many human patients. The aim of this book chapter is to give an overview of our current understanding and recent progress in energy expenditure control with specific emphasis on central control mechanisms.

Keywords: Body weight; Dorsomedial hypothalamus; FGF21; Hormones; Hypothalamus; Leptin; Neuronal circuits.

Fig. 1

Schematic view of the complex interaction of brain, peripheral tissues, and environment

Fig. 2

Temperature changes induce robust adaptations in energy expenditure. (a) Acute decreases in ambient temperature quickly and robustly increase energy expenditure. (b) Acute increase in ambient temperature results in adaptive decrease in energy expenditure

Fig. 3

Components of energy expenditure. Oxidative processes result in a proton-motive force in the mitochondrion used to generate ATP, even though basal proton leaks are observed that “wastes” energy. ATP production and basal proton leaks together account for obligatory metabolism, required for minimal bodily functions. The active uncoupling of proton-motive force from ATP production is used to generate heat, e.g., in the brown adipose tissue. And uncoupling protein 1 (UCP1) is a well-studied example for active uncoupling. Substrate cycling also actively contributes to heat production. Together these mechanisms account for facultative metabolism, which is optional and not used for baseline maintenance of bodily functions, e.g., at thermoneutral conditions

Fig. 4

Schematic overview of central circuits that modulate energy expenditure