Download Central Nervous System Control of Energy and Glucose

Central Nervous System Control of Energy and Glucose Homeostasis
Jong-Woo Sohn, MD, PhD
The central nervous system (CNS) neuronal circuits integrate peripheral and
central signals to appropriately regulate energy and glucose homeostasis. Serotonin 2C
receptors (5-HT2CRs) expressed by the anorexigenic (appetite-suppressing) proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus regulate food
intake and glucose balance. Recently, Belviq (lorcaserin, a specific 5-HT2CR agonist)
became the first FDA-approved diet pill in the last 15 years. However, the cellular
mechanisms for the beneficial metabolic effects of serotonin have remained largely
unknown. In the first part of my talk, I will discuss my recent findings that 5-HT2CRs
excite arcuate POMC neurons via the activation of the classical transient receptor
potential (TRPC) channels. POMC neurons release alpha-MSH which is an agonist at
the anorexigenic melanocortin 4 receptors (MC4Rs) in the CNS. Indeed, MC4Rs in the
CNS contribute to decrease food intake, increase energy expenditure, and improve
glucose balance. However, the expression of MC4Rs within the autonomic nervous
system (ANS; both sympathetic and parasympathetic) underlies the autonomic side
effects (e.g. hypertension) of MC4R agonists as a potential novel diet pill. Moreover, the
physiological benefit of MC4Rs activating both sympathetic and parasympathetic arms
of the ANS is not readily apparent. In the second part of my talk, I will discuss my recent
findings that MC4R agonists excite sympathetic preganglionic neurons in the spinal cord,
but inhibit parasympathetic preganglionic neurons in the brainstem. These findings
provide a cellular correlate of the autonomic side effects associated with MC4R agonists
and contribute to explain a physiological role for MC4Rs expressed in autonomic
preganglionic neurons.