Exercise, Obesity and CNS Control of Metabolic Homeostasis: A Review

Abstract

This review details the manner in which the central nervous system regulates metabolic homeostasis in normal weight and obese rodents and humans. It includes a review of the homeostatic contributions of neurons located in the hypothalamus, the midbrain and limbic structures, the pons and the medullary area postrema, nucleus tractus solitarius, and vagus nucleus, and details how these brain regions respond to circulating levels of orexigenic hormones, such as ghrelin, and anorexigenic hormones, such as glucagon-like peptide 1 and leptin. It provides an insight as to how high intensity exercise may improve homeostatic control in overweight and obese subjects. Finally, it provides suggestions as to how further progress can be made in controlling the current pandemic of obesity and diabetes.

Keywords: BDNF; GLP-1; exercise; ghrelin; hypothalamus; leptin; metabolic homeostasis; obesity.

Figure 1

This figure illustrates the major hypothalamic, midbrain, pontine, limbic system, brainstem, and gastrointestinal systems that contribute to the control of energy homeostasis. The impact of obesity, high fat- high energy diets, and moderate to vigorous intensity exercise on energy homeostasis is detailed. Not included is the lateral hypothalamic area which plays an important role in receiving sensory signals from the intestinal tract and liver. ACCUMB, nucleus accumbens; AgRP, agouti-related protein; α-MSF, alpha-melanocortin stimulating factor; AP, area postrema; ARH, arcuate hypothalamus; BAT, brown adipose tissue; BDNF, brain-derived neurotrophic factor; CA, central amygdala; CART, cocaine and amphetamine-regulated transcripts; CCK, cholecystokinin; D1R, dopamine receptor type 1; D2R, dopamine receptor type 2; GDF15, glial-cell-derived growth and differentiation neurotrophic factor 15; GDF15AL, GD15F receptor; GHSR, growth hormone secretagogue receptor (for ghrelin); Glut, glutamine; HIP, hippocampus; MC3R, melanocortin 3 receptor; MC4R, melanocortin 4 receptor; MSL, muscle; NPY, neurotropin Y; NTS, nucleus tractus solitarius; OB-R, leptin receptor; PP, pancreatic peptide; PYY, peptide YY; PBN, parabrachial nucleus; PVH, paraventricular hypothalamus; POMC, pro-opiomelanocortin; SNS, sympathetic nervous system; TrkB, BDNF receptor; VN, vagus nucleus; VMH, ventral medial hypothalamus. Symbols: [↑], exercise increases blood levels; [↓], exercise decreases blood levels; [T], therapeutic potential; (↑H), exercise increases hypothalamic levels; (↓), exercise decreases effect.