Neonatal androgenization in the female rat, facilitates metabolic syndrome development during

ANA ALZAMENDI, ANDRES GIOVAMBATTISTA, DANIEL CASTROGIOVANNI, ROLF C. GAILLARD, EDUARDO SPINEDI.

EEUU

Congreso; The Obesity Society. Annual Scientific Meeting Phoenix,AZ.; 2008

The Obesity Society

The aim of the present work was to determine whether neonatal androgenization in the female rat, could be able to modify fructose rich diet (FRD)-induced metabolic dysfunction at the adult age. For this purpose, 5 day-old female rats were i.p. injected with 50 ml of corn oil either alone (control, CT) or containing 1.25 mg of testosterone propionate (TP) and studied on day 100 of age. These groups of rats drunk during the last 3 weeks before studied either fructose 10 % (w/v, in tap water; CT-F10 and TP-F10) or not (CT-F0 and TP-F0). Results indicated that, on the experimental day, CT-F10 rats developed, among different metabolic markers monitored, an enhancement (p < 0.05 vs. CT-F0) in the peripheral levels of triglycerides and non esterified fatty acids. The early androgenization by itself (TP-F0) was able to induce a significant (p < 0.05 vs. CT-F0) increase in insulin and leptin plasma concentrations, while it decreased (p < 0.05 vs. CT-F0) adiponectin plasma levels. Moreover, FRD intake did enhance circulating levels of triglycerides and leptin in androgenized animals only (TP-F10). Parametrial adipose tissue (PMAT) mass resulted equally enlarged (p < 0.05 vs. CT-F0 rats) in normal rats submitted to FRD intake (group CT-F10) and in androgenized rats (group TP-F0) (Figure 1). PMAT ob mRNA expression, although not modified by FRD intake in normal rats (CT-F10), was augmented (p < 0.05 vs. CT-F0) by the early androgenization, and additionally increased (p < 0.05 vs. TP-F0) by FRD intake (Figure 1). Finally, data from in vitro incubations of isolated PM adipocytes from all groups of adult rats indicated that neonatal androgenization (TP-F0) induced a significant (p < 0.05) impairment in insulin-stimulated leptin secretion by isolated adipocytes, regardless of FRD intake. Thus our study strongly suggests that the impact of early androgenization in the female rat: a) enhanced adiposity, b) induced adipose tissue endocrine dysfunction and, c) impaired insulin sensitivity, at the reproductive age. Our study strongly supports that impaired insulin sensitivity seems to be dependent, at least in part, on hyperandrogenicity-induced low adiponectinemia. Thus predisposing the organism for a fast development of FRD-induced metabolic syndrome.