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

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Abstract

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.

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Acknowledgments

Authors are indebted to Mr. O Vercellini and Mrs. C Ferese for animal care and histological preparations, respectively. The editorial assistance of Mrs. G. Vigo is recognized. This work was supported by grants from FONCyT (PICT 1051-2007) and CONICET (PIP 0704), Argentina, and FPRE (07-09), Switzerland.

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Correspondence to Eduardo Spinedi.

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Perelló, M., Cónsole, G., Gaillard, R.C. et al. Analysis of angiotensin II- and ACTH-driven mineralocorticoid functions and omental adiposity in a non-genetic, hyperadipose female rat phenotype. Endocr 37, 497–506 (2010). https://doi.org/10.1007/s12020-010-9335-3

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  • DOI: https://doi.org/10.1007/s12020-010-9335-3

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