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.

Addiction-like Synaptic Impairments in Diet-Induced Obesity.

Background: There is increasing evidence that the pathological overeating underlying some forms of obesity is compulsive in nature and therefore contains elements of an addictive disorder. However, direct physiological evidence linking obesity to synaptic plasticity akin to that occurring in addiction is lacking. We sought to establish whether the propensity to diet-induced obesity (DIO) is associated with addictive-like behavior, as well as synaptic impairments in the nucleus accumbens core considered hallmarks of addiction.