Melatonin Prevents Immune Stimulation of Pituitary ACTH production in Rats Fed Sucrose Rich Diets

CALANNI, JS; MARÍA ELISA MERCAU; MARCOS ARANDA; SILVIA SANCHEZ PUCH; ESTEBAN M. REPETTO,; CORA B. CYMERYNG

Chicago

Congreso; 100th Annual Meeting of the Endocrine Society; 2018

Endocrine Society

Excessive consumption of simple carbohydrates has been associated with an increased incidence of insulin resistance and obesity. Several reports have shown a concomitant dysfunction of the hypothalamus­ pituitary­ adrenal (HPA) axis in these patients. We have previously reported that rats fed a sucrose­ rich diet (SRD, 30% sucrose in the drinking water) for 7 weeks show a significant decrease in insulin sensitivity. Analysis of HPA axis activity 3 weeks after the initiation of the dietary modification, when changes in insulin sensitivity were still not evident, showed augmented levels of circulating ACTH and a higher pituitary expression of POMC that was accompanied by an increase in oxidative stress parameters. As a chronic low-grade inflammatory state has been associated with the development of insulin resistance and type 2 diabetes and several inflammatory cytokines have been shown to activate the HPA axis, we designed present experiments to analyze the involvement of inflammation on the observed pituitary dysfunction. Animals were randomly distributed in 4 groups: 1) Control, 2) SRD, 3) Mel and 4) SRD + Mel. In groups 3 and 4, subcutaneous melatonin implants were surgically implanted and changed every ten days. Animals were sacrificed after 3 weeks and pituitary glands were dissected and processed to obtain protein and RNA. Plasma ACTH levels were assessed by a chemiluminiscent assay and corticosteronemia was determined by RIA. Expression of specific proteins and mRNAs were evaluated by western blot and RT-qPCR respectively. AtT20 (murine corticotrophs) and J774 (murine macrophages) cells were used in in vitro experiments.Compared to the corresponding controls our results showed an increase in the mRNA levels of TNFα (p