Hypothalamic GABAergic Neurons Expressing Cellular Retinoic Acid Binding Protein 1 (CRABP1) Are Sensitive to Metabolic Status and Liraglutide in Male Mice.

Introduction: Owing to their privileged anatomical location, neurons of the arcuate nucleus of the hypothalamus (ARC) play critical roles in sensing and responding to metabolic signals such as leptin and glucagon-like peptide 1 (GLP-1). In addition to the well-known proopiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurons, subpopulations of GABAergic neurons are emerging as key regulators of energy balance. However, the precise identity of these metabolic neurons is still elusive.

Histaminergic regulation of food intake.

Histamine is a biogenic amine that acts as a neuromodulator within the brain. In the hypothalamus, histaminergic signaling contributes to the regulation of numerous physiological and homeostatic processes, including the regulation of energy balance. Histaminergic neurons project extensively throughout the hypothalamus and two histamine receptors (H1R, H3R) are strongly expressed in key hypothalamic nuclei known to regulate energy homeostasis, including the paraventricular (PVH), ventromedial (VMH), dorsomedial (DMH), and arcuate (ARC) nuclei.

A critical update on the leptin-melanocortin system.

The discovery of leptin in 1994 was an "eureka moment" in the field of neurometabolism that provided new opportunities to better understand the central control of energy balance and glucose metabolism. Rapidly, a prevalent model in the field emerged that pro-opiomelanocortin (POMC) neurons were key in promoting leptin's anorexigenic effects and that the arcuate nucleus of the hypothalamus (ARC) was a key region for the regulation of energy homeostasis. While this model inspired many important discoveries, a growing body of literature indicates that this model is now outdated.

Do POMC neurons have a sweet tooth for leptin? Special issue: Role of nutrients in nervous control of energy balance.

Coordinated detection of changes in metabolic state by the nervous system is fundamental for survival. Hypothalamic pro-opiomelanocortin (POMC) neurons play a critical role in integrating metabolic signals, including leptin levels. They also coordinate adaptative responses and thus represent an important relay in the regulation of energy balance.

New Horizons: Is Obesity a Disorder of Neurotransmission?

Obesity is a disease of the nervous system. While some will view this statement as provocative, others will take it as obvious. Whatever our side is, the pharmacology tells us that targeting the nervous system works for promoting weight loss.

Mitochondrial uncoupling in the melanocortin system differentially regulates NPY and POMC neurons to promote weight-loss.

Objective: The mitochondrial uncoupling agent 2,4-dinitrophenol (DNP), historically used as a treatment for obesity, is known to cross the blood-brain-barrier, but its effects on central neural circuits controlling body weight are largely unknown. As hypothalamic melanocortin neuropeptide Y/agouti-related protein (NPY/AgRP) and pro-opiomelanocortin (POMC) neurons represent key central regulators of food intake and energy expenditure we investigated the effects of DNP on these neurons, food intake and energy expenditure.

Method: C57BL/6 and melanocortin-4 receptor (MC4R) knock-out mice were administered DNP intracerebroventricularly (ICV) and the metabolic changes were characterized.