Table 1.
CNS control of metabolic homeostasis.
| Structure | Neurons, receptors | Effect on energy intake/expenditure | Function in obesity or high fat/energy diet | Effect of exercise |
|---|---|---|---|---|
| HYPOTHALAMUS arcuate & ventromedial nuclei |
AgRP/NPY neurons POMC/CART neurons MC3R, MC4R |
Orexigenic, ↓ energy expenditure Anorexigenic Anorexigenic, ↑energy expenditure |
Resistant to suppression by leptin, insulin; ↓ synapses. Resistant to activation by leptin, suppression by NPY, ↓ neurogenesis MC4R loss causes hyperphagic obesity, insulin resistance |
↓ insulin, leptin resistance, ↑ leptin receptor expression, transmission, ↓ghrelin in hypothalamus ↓ leptin resistance, Prevents hyperphagic obesity in young MC4R −/− mice |
| MIDBRAIN meso-accumbens dopamine system |
D1R, D2R, MC4R, GHSR+ neurons | Regulate voluntary food intake and energy expenditure (running, locomotion). | ↓ energy expenditure due to ↓ D2R+ neuron signaling in nucleus accumbens | Short-term anorexia, ↓weight if energy expenditure > intake |
| PONS parabrachial nucleus |
Calcitonin gene-related peptide+ neurons | Primarily anorexigenic (taste aversions, taste preferences). | ↓ taste response to sucrose in CCK-1R −/- obese mice | ↑ ANS and somatosensory gene expression |
| MEDULLA area postrema, NTS, & vagus* |
GDF15R+, MC4R+, ANS neurons |
Orexigenic signals: ghrelin Anorexigenic signals: leptin, CCK, GLP-1, PYY, GDF15, BDNF |
Impaired anorexigenic signals & circadian rhythms in NTS | ↑ SNS-mediated energy expenditure; ↓ghrelin signaling, ↑GDF15 signaling |
| DIENCEPHALON olfactory bulb |
Olfactory nerves | Anosmia: anorexigenic; ↑energy expenditure Hyperosmia: orexigenic; ↓energy expenditure | Enhanced sense of smell, ↑appetite, ↓energy expenditure | Unknown |
*
The vagal nucleus tractus solitarius and vaso-vagal pathways play a preeminent role in the rapid & often persistent remission of type 2 diabetes and the metabolic syndrome in persons undergoing bariatric surgery. AgRP, agouti-related protein; ANS, autonomic nervous system; BDNF, brain-derived neurotrophic factor; CCK, cholecystokinin; CCK-1R, cholecystokinin receptor 1; D1R, dopamine receptor type 1; D2R, dopamine receptor type 2; GDF15, glial-cell-derived growth and differentiation neurotrophic factor 15; MC3R, melanocortin 3 receptor; MC4R, melanocortin 4 receptor; NPY, neurotropin Y; NTS, nucleus tractus solitarius; POMC, pro-opiomelanocortin; SNS, sympathetic nervous system.