Moderate exercise prevents pituitary dysfunction induced by a sucrose rich diet

MERCAU, MARÍA E.; REPETTO, EM; ARIAS, P; FINKIELSTEIN CV; CYMERYNG, CORA B

Estocolmo

Congreso; 51th Annual Meeting of the European Association for the Study of Diabetes; 2015

European Association for the Study of Diabetes

Background and aims: Increased consumption of sucrose, a major constituent of western diet, has been associated with the development of obesity and insulin resistance (IR). Altered hypothalamic-pituitary-adrenal axis function has been linked to to IR, in animal models and patients. Studies from our group have shown morphological and functional changes in the adrenal cortex of rats fed a sucrose-rich diet (SRD). The aim of this study was to evaluate the effects of SRD on basal activity of the pituitary gland, the underlying cellular processes, and the effect of exercise (E) on these parameters.Materials and methods: Adult male Wistar rats were randomized into 4 groups (n=5), two of which received 30% w/v sucrose in the drinking water (SRD) for 15 weeks. A subset of each dietary group was subjected to E protocol (C-E and SRD-E) (treadmill walk, 15 min/day, 5 day/week, for 15 weeks, at 0.8km/h speed). The sedentary (C-S and SRD-S) subset of each dietary group did not perform any physical activity. Insulin sensitivity was assessed at the 7th week of treatment by i.p. ITT. Statistical analyses were performed using Student?s t test or ANOVA and significant differences were studied with Tukey?s post hoc test.Results: Our results showed that serum metabolites (fasting glucose, triglycerides and free fatty acids (FFA)) were increased in SRD-S animals by the end of the 15th week of treatment. Animals from the SRD-S group showed significantly lower plasma levels of ACTH (C-S: 96.9 ± 2.6, SRD-S: 52.6 ± 0.5, pg/ml), decreased pituitary POMC mRNA levels (C-S: 1.02 ± 0.04, SRD-S: 0.64 ± 0.03, fold induction), and lower serum corticosterone concentrations (C-S: 13.61 ± 2.66, SRD-S: 2.66 ± 0.33, ng/ml) than those from the C-S group. Analysis of pituitary levels of antioxidant enzymes and autophagy markers suggested the activation of these cellular pathways in the SRD-S group. E was able to prevent the induction of autophagy and antioxidant defense systems in the pituitary gland of SRD-E animals. Analysis of POMC mRNA (C-E: 1.46 ± 0.06, SRD-E: 1.43 ± 0.18, fold induction), plasma ACTH levels (C-E: 142.0 ± 8.6, SRD-E: 130.6 ± 20.2, pg/ml) and of serum corticosterone concentrations (C-E: 28.05 ± 4.8, SRD-E: 50.40 ± 3.33, ng/ml) showed that E prevented the effects of SRD on HPA axis basal activity. Regarding the analyzed serum biochemical parameters, E was able to prevent the increase in serum FFA levels. Given this, we analyzed the effects of palmitic acid (PA) on POMC-ACTH production in AtT-20 corticotroph cell-line. Cells were transiently transfected with a POMC-luciferase reporter plasmid, and then incubated with 4% BSA ± PA. Our results showed that 24 h treatment with 1mM PA significantly inhibited POMC promoter activity (4% BSA: 1.00 ± 0.07, 4% BSA + 1mM PA: 0.75 ± 0.04, A.U.), and induced autophagy and oxidative stress. Similar results on POMC promoter activity were obtained incubating the cells with Rapamycin or H2O2, suggesting a role for these cellular processes on POMC regulation.Conclusion: Administration of a SRD shows a significant effect on cellular mechanisms that influence POMC transcription and ACTH production in corticotroph cells. We also hypothesize that sustained elevated FFA serum levels could contribute to the observed pituitary dysfunction.