INSULIN SENSITIZATION WITH A PPAR GAMMA AGONIST PREVENTS ADRENOCORTICAL LIPID INFILTRATION AND SECRETORY CHANGES INDUCED BY A HIGH SUCROSE DIET

MARTINEZ CALJEMAN, CAMILA; DI GRUCCIO, JUAN MARTÍN; SANCHEZ, ROCÍO; REPETTO, ESTEBAN M.; ASTORT, FRANCISCO; MERCAU, MARÍA ELISA; PANDOLFI, MATÍAS; BERG, GABRIELA; SHREIER, LAURA; ARIAS, PABLO; CYMERYNG, CORA B.

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2012 vol. 214 p. 267 - 276

0022-0795

Patients with chronic hypercortisolism display a cluster of abnormalities similar to those detected in subjects affected by insulin resistance (IR), and it has been hypothesized that deviations in glucocorticoid secretion and/or action may contribute to somatic and biochemical changes observed in patients with IR. We analyzed changes in rat adrenocortical function and morphology associated to the development of IR, generated in male adult rats by the addition of 30% sucrose to the drinking water. Caloric intake, body and adipose tissue weights and biochemical parameters were determined throughout the duration of this treatment. Expression levels of StAR, CYP11A1, and MC2R were evaluated by RT-PCR, histochemical analysis of the adrenal cortex was performed using Masson's trichrome and Sudan III staining, and corticosterone levels were measured by RIA. After seven weeks of sucrose administration higher serum glucose, insulin and triglyceride levels and an altered glycemic response to an i.p. insulin test were detected. Adrenal glands showed a neutral lipid infiltration (triglycerides + cholesterol). Furthermore, sucrose-treated animals exhibited higher basal corticosterone levels and a blunted response to ACTH injection. An increase in StAR and CYP11A1 and a decrease in MC2R levels were also found. Noteworthy, the instauration of adrenocortical (functional and histological) abnormalities was prevented in sucrose-treated rats by the simultaneous administration of a PPAR-γ agonist. Sucrose-induced IR may affect adrenocortical function and morphology indirectly (altering CRH/ACTH secretion) or directly, by means of adipokines or lipid metabolites generated within the adrenal gland. These abnormalities are prevented by the administration of a PPARγ agonist.