EFFECTS OF MELATONIN TREATMENT ON INFLAMMATORY MARKERS AND PITUITARY DYSFUNCTION IN INSULIN RESISTANT RATS

CALANNI, JS; MERCAU, MARÍA E.; WISZNIEWSKI, M; ARANDA, M; SANCHEZ PUCH, S; VECINO, CV; REPETTO, EM; CYMERYNG, CB

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAIC-SAIB-SAI-SAA-SAB-SAB-SAFE-SAFIS-SAH-SAP

Excessive consumption of diets with high sugar content has beenassociated with an increased incidence of insulin resistance andobesity. Several reports have shown a concomitant dysfunction ofthe hypothalamus pituitaryadrenal(HPA) axis in these patients.We have previously reported that rats fed a sucrose richdiet (SRD,30% sucrose in the drinking water) for 7 weeks show a significantdecrease in insulin sensitivity. Analysis of HPA axis activity after 3weeks of treatment, when changes in insulin sensitivity were still notevident, showed augmented levels of circulating ACTH and a higherpituitary expression of POMC that was accompanied by an increasein oxidative stress parameters.Present experiments were designed to analyze the involvementof inflammation-related effects 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, subcutaneousmelatonin implants (10mg) were surgically implanted. Animals weresacrificed after 3 weeks and pituitary glands were processed to obtainprotein and RNA.Results showed an increase in mRNA levels of TNFα (p<0.001)and inflammasome components (ASC, NALP3, IL-1beta, p<0.01 vs.C) in the SRD group that was prevented by melatonin treatment. Inaddition, immunohistochemistry analysis of pituitary tissues indicatedan increase in both ACTH and Iba1 positive signals in the SRDgroupthat were attenuated in the SRD-Mel group. Western blotstudies also showed higher levels of the macrophage marker F4-80in the SRD-group. In vitro studies, in the corticotroph AtT20 cell line,showed the induction of POMC by conditioned media obtained fromperitoneal macrophages or from J774 cells stimulated with LPS.In summary, our results suggest that changes in the synthesis andsecretion of ACTH detected in SRD-treated rats could be involvedthe activation of inflammation-related pathways.