Genetic obesity syndromes in mouse and man have led to an appreciation of a neural network of interacting, phenotypically distinct, neurons in the hypothalamus that are important for the central regulation of appetite and body weight. The network is composed of leptin-sensitive neurons that express either the agonist or antagonist of the melanocortin-4 receptor (MC4R) on the MC4R-expressing neurons. The inter- and intraneuronal signaling that occurs in this network of “obesity neurons” is reviewed and a new approach is described for the mining of these neurons for novel anti-obesity drug targets.
Keywords: obesity, pro-opiomelanocortin (pomc), agouti-related peptide (agrp), neuropeptide y (npy), laser-capture microdissection (lcm), gene profiling, signaling
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