Morphological and functional changes detected in rat adrenal cortex during the induction of insulin resistence by means of a sucrose-rich diet

MARTINEZ CALEJMAN C; REPETTO E.M.; ASTORT F.; DI GRUCCIO J.M.; SÁNCHEZ R.; MERCAU M.; ARIAS P.; CYMERYNG C. B.

San Diego, EEUU

Congreso; The Endocrine Society’s 92nd Annual Meeting – ENDO 2010; 2010

The Endocrine Society

Body: Hyperactivation of the hypothalamic-pituitary-adrenal axis (HPAA) has been demonstrated both in humans and animals with insulin resistance (IR), but evidence on a direct adrenocortical impact of IR-associated abnormalities (e.g. elevated serum insulin, triacylglycerides and/or FFA levels, oxidative stress, inflammatory state) is lacking. We evaluated, in adult male Wistar rats fed a sucrose-enriched diet (SED, sucrose 30% w/v in drinking water), the presence of changes in adrenocortical structure and function (corticosterone secretion, insulin signaling, and expression of nitric oxide synthase (NOS) and cyclooxygenase 2 (COX-2), two well known local modulators of steroidogenesis). As compared to control animals, SED-treated rats showed, after 7 weeks, higher fasting serum glucose (130.6 vs. 74.5 mg/dl; p<0.001), triacylglyceride (604.60 vs. 104.52 mg/dl; p<0.001) and insulin concentrations (2.0 vs. 1.0 ng/ml; p<0.005), as well as elevated basal serum corticosterone levels (6.6 vs. 9.6 ng/ml; p<0.001). At this time point, impaired insulin signaling (i.e., lower phosphorylated Akt levels) and increased NOS activity and expression levels of eNOS, iNOS, COX-2, StAR and of the macrophage marker F4/80 were detected in adrenocortical homogenates obtained from the SED group. Interestingly, adrenal glands of SED-treated animals showed a significant lipidic infiltration, as demonstrated by histochemistry. In a second series of experiments rosiglitazone (RSG), a PPAR agonist, administered during SED treatment, reverted the observed changes in NOS activity and corticosterone levels and diminished adrenocortical lipidic infiltration.In summary, SED-associated IR might affect adrenocortical cells by inducing lipidic infiltration. Without disregarding possible effects exerted at higher levels of the HPAA and/or on steroid metabolism, the observed changes in steroid production could be attributed to effects of locally produced adipokines or lipid metabolites. Also augmented inflammatory activity could result in COX-2 activation, thus increasing steroid production. In addition, augmented NO generation could trigger post-transcriptional modifications of proteins involved in steroid biosynthesis and/or its modulation. These changes were reverted by RSG, by means of previously described effects (diminished insulin resistance and lipidic infiltration, reduced systemic inflammation, suppression of COX-2 activity), and/or perhaps through other still unknown mechanisms.