POMC

Targeting the brain to improve obesity and type 2 diabetes

The increasing prevalence of obesity and type 2 diabetes (T2D) and associated morbidity and mortality emphasizes the need for a more complete understanding of the mechanisms mediating energy homeostasis to accelerate the identification of new medications. Recent reports indicate that obesity medication, 5-hydroxytryptamine (5-HT, serotonin)2C receptor (5-HT2CR) agonist lorcaserin improves glycemic control in association with weight loss in obese patients with T2D. We examined whether lorcaserin has a direct effect on insulin sensitivity and how this effect is achieved. We clarify that lorcaserin dose-dependently improves glycemic control in a mouse model of T2D without altering body weight. Examining the mechanism of this effect, we reveal a necessary and sufficient neurochemical mediator of lorcaserin’s glucoregulatory effects, via activation of brain pro-opiomelanocortin (POMC) peptides. We observed that lorcaserin reduces hepatic glucose production and improves insulin sensitivity. These data suggest that lorcaserin’s action within the brain represents a mechanistically novel treatment for T2D: findings of significance to a prevalent global disease.

Neurocircuits in control of integrative physiology

This open colloquia session is part of the special workshop entitled "Obesity at the Interface of Neuroscience and Physiology II". Abstract: Proopiomelanocortin (POMC)- and agouti related peptide (AgRP)-expressing neurons in the arcuate nucleus of the hypothalamus (ARH) are critical regulators of food intake and energy homeostasis. They rapidly integrate the energy state of the organism through sensing fuel availability via hormones, nutrient components and even rapidly upon sensory food perception. Importantly, they not only regulate feeding responses, but numerous autonomic responses including glucose and lipid metabolism, inflammation and blood pressure. More recently, we could demonstrate that sensory food cue-dependent regulation of POMC neurons primes the hepatic endoplasmic reticulum (ER) stress response to prime liver metabolism for the postpramndial state. The presentation will focus on the regulation of these neurons in control of integrative physiology, the identification of distinct neuronal circuitries targeted by these cells and finally on the broad range implications resulting from dysregulation of these circuits as a consequence of altered maternal metabolism.

SELENOT is a guardian of ER homeostasis in POMC neurons

Thalamic opioids from POMC satiety neurons gate sugar appetite

FENS Forum 2024

The development of MC3R neurons, AgRP and POMC neuronal projections and the maintenance of intra-hypothalamic neuronal circuits

H3K27 demethylase Kdm6a/Utx controls Ngn3, Pomc and Npy expression in a sex-specific way in the developing neuroendocrine hypothalamus

CB1 receptors in POMC neurons coordinate responses to fear and food

Single-cell molecular and functional mapping of POMC neurons in obesity: a multi-modal approach

Extracellular vesicles from hypothalamic astrocytes modify transcription factors of the leptin signaling pathway in proopiomelanocortin (POMC) neurons

FENS Forum 2024

Hypothalamic POMC-TRPM2-mediated regulation of interscapular BAT thermogenesis

FENS Forum 2024

Role of EphrinB3 in POMC neurons in the control of energy and glucose homeostasis

FENS Forum 2024