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

CALANNI, JS; MERCAU, M; ARANDA, M; SANCHEZ PUCH, S; REPETTO, EM; CYMERYNG, CB

CABA

Congreso; 4th INTERNATIONAL CONGRESS IN TRANSLATIONAL MEDICINE; 2018

FFYB-UBA

Several studies have established a link between excessiveconsumption of simple carbohydrates and the increased incidence of insulinresistance (IR) and obesity registered worldwide. Many of these patients alsoshow a concomitant dysfunction of the hypothalamus pituitary adrenal (HPA)axis. We have previously reported that feeding rats asucrose rich diet (SRD, 30% sucrose in the drinking water) was associated withthe hyperactivation of the HPA axis, as early as 3 weeks after the initiationof the diet and IR after 7 weeks of treatment. Present experiments weredesigned to evaluate possible mechanisms involved in the HPA axis dysfunctionafter 3 weeks of SRD treatment.Our results showed that augmented levels of circulatingACTH and an increased expression of POMC were accompanied by changes inoxidative stress (OxS) and inflammatory parameters in pituitary tissues. Sincea chronic low-grade inflammatory state has been associated with the developmentof IR, and several inflammatory cytokines have been shown to activate the HPAaxis, we hypothesized the involvement of pituitary OxS and inflammation in thestimulation of ACTH production from corticotroph cells. To test this hypothesiswe analyzed the effect of melatonin, a molecule with potent anti-oxidant andanti-inflammatory properties, on POMC/ACTH production both in vivo and in vitro. In-vivo experiments: Wistar rats werefed standard chow and water or a SRD. Melatonin pellets were surgicallyimplanted in a group of animals. After 3 weeks of treatment pituitary glandswere processed to obtain total proteins and RNA. Plasma ACTH levels wereassessed by a chemiluminiscent assay and serum corticosterone concentration wasdetermined by RIA. Expression of specific proteins and mRNAs were evaluated bywestern blot and RT-qPCR. Results showed that melatonin treatment prevented theincreases in pituitary POMC expression levels and in circulating levels of ACTHand corticosterone observed in the SRD group. A closer examination intopituitary tissues showed an increase in the mRNA levels of TNFα, IL-1 beta and inflammasome components (NLRP3, ASC,Caspase-1), and also in the expression levels of Iba-1 and F4-80 as determinedby immunofluorescence and immunoblot assays. These changes were prevented by melatonintreatment.