Analysis of angiotensin II- and ACTH-driven mineralocorticoid functions and omental adiposity in a non-genetic, hyperadipose female rat phenotype.
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.
Neuroendocrine Unit, Multidisciplinary Institute on Cell Biology (CONICET-CICPBA), PO Box 403, 1900 La Plata, Argentina.
Mario
M
Perelló
Gloria
G
Cónsole
Rolf C
RC
Gaillard
Eduardo
E
Spinedi
D050154:Adiposity / Q000187:drug effects; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D007031:Hypothalamus / Q000187:drug effects*; D009852:Omentum / Q000166:cytology; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D012970:Sodium Glutamate / Q000633:toxicity
D000804:Angiotensin II; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012970:Sodium Glutamate