Neuroendocrine deregulation of food intake, adipose tissue and the gastrointestinal system in obesity and metabolic syndrome

Obesity is an excess of fat mass. Fat mass is an energy depot but also an endocrine organ. A deregulation of the sympathetic nervous system (SNS) might produce obesity. Stress exaggerates diet-induced obesity. After stress, SNS fibersreleaseneuropeptideY(NPY)whichdirectlyincreases visceral fat mass producing a metabolic syndrome (MbS)like phenotype. Adrenergic receptors are the main regulators of lipolysis. In severe obesity, we demonstrated that the adrenergic receptor subtypes are differentially expressed in different fat depots. Liver and visceral fat share a common sympathetic pathway, which might explain the low-grade inflammationwhichsimultaneouslyoccursinliverandfatof the obese with MbS. The neuroendocrine melanocortinergic system and gastric ghrelin are also greatly deregulated in obesity. A specific mutation in the type 4 melanocortin receptor induces early obesity onset, hyperphagia and insulinresistance. Nonetheless, it was recently discovered that a mutation in the prohormone convertase 1/3 simultaneously produces severe gastrointestinal dysfunctions and obesity.