Analysis of angiotensin II- and ACTH-driven mineralocorticoid functions and omental adiposity in a non-genetic, hyperadipose female rat phenotype

作者：Perello Mario; Console Gloria; Gaillard Rolf C; Spinedi Eduardo^*

来源：Endocrine, 2010, 37(3): 497-506.

DOI：10.1007/s12020-010-9335-3

• Hypothalamic obesity
• Hypophagia
• Mineralocorticoid
• Omental adiposity
• Glucocorticoid
• Leptin
• Insulin

The hypothalamic damage induced by neonatal treatment with monosodium l-glutamate (MSG) induces several metabolic abnormalities, resulting in a rat hyperleptinemic-hyperadipose phenotype. This study was conducted to explore the impact of the neonatal MSG treatment, in the adult (120 days old) female rat on: (a) the in vivo and in vitro mineralocorticoid responses to ACTH and angiotensin II (AII); (b) the effect of leptin on ACTH- and AII-stimulated mineralocorticoid secretions by isolated corticoadrenal cells; and (c) abdominal adiposity characteristics. Our data indicate that, compared with age-matched controls, MSG rats displayed: (1) enhanced and reduced mineralocorticoid responses to ACTH and AII treatments, respectively, effects observed in both in vivo and in vitro conditions; (2) adrenal refractoriness to the inhibitory effect of exogenous leptin on ACTH-stimulated aldosterone output by isolated adrenocortical cells; and (3) distorted omental adiposity morphology and function. This study supports that the adult hyperleptinemic MSG female rat is characterized by enhanced ACTH-driven mineralocorticoid function, impaired adrenal leptin sensitivity, and disrupted abdominal adiposity function. MSG rats could counteract undesirable effects of glucocorticoid excess, by developing a reduced AII-driven mineralocorticoid function. Thus, chronic hyperleptinemia could play a protective role against ACTH-mediated allostatic loads in the adrenal leptin resistant, MSG female rat phenotype.

• 出版日期2010-6