Central regulation of energy balance

S yn A simple outline of the complex regulatory system o p s that controls energy balance: altered nutritional status is provokes changes in circulating hormones and endogenously produced steroids which provide a feedback signal to the CNS to alter energy balance. Both the long-term regulatory signals derived from adipose and the short-term regulatory signals derived from stomach and the classic endocrine organs, form an important integrated peripheral afferent signals acting directly on the neurons and astrocytes in the hypothalamic regions of the brain. Tanycytes have recently been identified as important ependymal cells that transfer signals from the CSF to CNS. The hypothalamic arcuate nucleus often orchestrates the coordinated regulation of energy balance by projecting to second order neurons within other key hypothalamic regions implicated in feeding and appetitive behaviour (e.g. PVN, DMN, VMN & LH).

Central to the hypothalamic regulatory system are the two prominent arcuate neuron sub-populations, the orexigenic NPY/AGRP and the anorexigenic POMC/CART containing neurons. Outside the hypothalamus, multiple sites within the mesolimbic regions (e.g. VTA, Amygdala, Nucleus accumbens) are likely to be involved in the motivation to find and eat rewarding foods. Addionally, projections to the autonomic centers in the hindbrain (e.g NTS, AP & DMN) and spinal cord mediate autonomic outflow to the peripheral organs including the gut and adipose tissue.

K e GHSR Insulin Receptor ObR y

Glucose receptor Neuron

A b b r AGRP Agouti related peptide MCH Melanin Concentrating Hormone ev ia AMPK AMP activated protein kinase ME Median eminence tio n AP Area Postrema NPY Neuropeptide Y s ARC Arcuate nucleus NPY1R Neuropeptide Y Y1 receptor BAT Brown Adipose Tissue NPY2R Neuropeptide Y Y2 receptor BDNF Brain Derived Neurotrophic Factor NPY5R Neuropeptide Y Y5 receptor BSX Brain specific homeobox NT Neurotensin CART Cocaine and Amphetamine Regulated Transcript NTS Nucleus of the solitary tract CB1 Cannabinoid 1 ObR Leptin Receptor CCKR Cholecystokinin Receptor OXM Oxyntomodulin CNS Central Nervous System OXY Oxytocin CRH Corticotropin Releasing Hormone PACAP Neuropeptide pituitary adenylate cyclase DMN Dorsal Medial Nucleus activating polypeptide DMV Dorsal Motor nubleus of the Vagus POMC Pro Opiomelanocortin ESR Estrogen receptor PVN Paraventricular nucleus FTO Fat mass and obesity-associated protein PYY 3-36 Peptide YY (PYY) GABA Gamma Amino Butyric Acid Sf1 Steroidogenic factor 1 GABAR Gamma Amino Butyric Acid Receptor Sim1 Single minded 1 GHRH Growth Hormone Releasing Hormone T4 Thyroxine GHSR Growth Hormone Secretagogue Receptor TRa Thyroid Receptor alpha GIP Gastric Inhibitory Polypeptide TRH Thyrotropin Releasing Hormone GLR1R Glucagon Like Peptide 1 Receptor VMN Ventral Medial Nucleus 5HT2CR Serotonin Receptor VTA Ventral Tegmental Area LH Lateral Hypothalamus WAT White Adipose Tissue S

MC3R Melanocortin 3 Receptor 3V Third ventricle B M _ 2

MC4R Melanocortin 4 Receptor 1 _ 0 2 5

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