Pathogenesis of the Metabolic Syndrome: Insights from Monogenic Disorders

Figure 1

Diagram showing the sites of known monogenic causes of obesity which affect the central regulators of appetite. Leptin is one of the major adiposity signals which circulates to the brain in the region of the arcuate nucleus (ARC) within the hypothalamus and binds to its receptors located in two groups of ARC neurons. Leptin action promotes the synthesis of proopiomelanocortin (POMC) which is cleaved to α-melanocyte stimulating hormone (αMSH), a neurotransmitter which acts at melanocortin 4 receptors (MC4R) on neurons in other hypothalamic areas to reduce food intake. Leptin acts to inhibit the synthesis and secretion of Agouti-related peptide (AgRP) from the second group of ARC neurons, which is an antagonist at MC4R.