Hyperphagia in obesity is associated with a central peptidergic dysregulation in rats.
Hyperphagia and obesity are often associated, and the origins of the biochemical modifications leading to these syndromes might be in the hypothalamus. Indeed, food intake is regulated by numerous neuropeptides in various hypothalamic nuclei, including the paraventricular (PVN), arcuate (ARC), ventromedian (VMN) and suprachiasmatic (SCH) nuclei. Among these peptides, neuropeptide Y (NPY) is the most potent inducer of food intake whereas neurotensin (NT) decreases food intake. We measured these two peptides in microdissected hypothalamic nuclei in obese Zucker rats that ate 30% more food than their lean counterparts. Neuropeptide Y and neurotensin levels varied in opposite directions: In the hyperphagic obese Zucker rats, the NPY concentrations were significantly greater than those in the lean normophagic rats in the ARC (+30%), PVN (+60%) and SCH (+94%) nuclei, whereas the NT levels were significantly lower in the ARC (-40%), PVN (-31%) VMN (-66%) and SCH (-47%) nuclei. Both these variations tend to increase food intake. Feeding periodicity might also be modified because large variations of the two peptides have been measured in the supra-chiasmatic nucleus, which is considered the most important regulator of feeding rhythm. The results reinforce the hypothesis that hyperphagia in obesity is associated with a biochemical modification in the central nervous system because the peripheral status of NT and NPY was not modified in the obese rats. Because levels of other hypothalamic peptides, such as opioid peptides and somatostatin, are also slightly modified, it can be concluded that hyperphagia in obesity is associated with a central peptidergic dysregulation. Research on drugs reacting specifically with the receptor of these peptides might have interesting implications for the treatment of hyperphagia and, therefore, of obesity.
Beck
B
B
Institut National de la Santé et de la Recherchee Medicale (INSERM) U. 308, Mécanismes de Régulation du Compartement Alimentaire, Nancy, France.
Burlet
A
A
Nicolas
J P
JP
Burlet
C
C
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000032:analysis / Q000503:physiopathology; D004195:Disease Models, Animal; D006963:Hyperphagia / Q000150:complications / Q000209:etiology*; D007031:Hypothalamus / Q000032:analysis / Q000503:physiopathology*; D009478:Neuropeptide Y / Q000032:analysis / Q000502:physiology*; D009496:Neurotensin / Q000032:analysis / Q000502:physiology*; D009765:Obesity / Q000150:complications*; D010286:Paraventricular Hypothalamic Nucleus / Q000032:analysis / Q000503:physiopathology; D051381:Rats; D011924:Rats, Zucker; D014697:Ventromedial Hypothalamic Nucleus / Q000032:analysis / Q000503:physiopathology
D009478:Neuropeptide Y; D009496:Neurotensin