Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction.
We investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment) on liver oxidative stress (OS), inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a) OS (GSH and protein carbonyl groups) and inflammatory (IL-1b, TNFa, and PAI-1) biomarkers and (b) carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity) and fructokinase (mRNA). Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity) and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs) were increased. In conclusion adult MSG rats developed an insulin-resistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis. These features, shared by both metabolic and Cushing's syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation.
Centro de Endocrinología Experimental y Aplicada (CENEXA), UNLP-CONICET-FCM, 1900 La Plata, Argentina.
Hernán Gonzalo
0000-0001-7172-1612
HG
Villagarcía
Centro de Endocrinología Experimental y Aplicada (CENEXA), UNLP-CONICET-FCM, 1900 La Plata, Argentina.
Vanesa
0000-0002-8231-4307
V
Sabugo
Centro de Endocrinología Experimental y Aplicada (CENEXA), UNLP-CONICET-FCM, 1900 La Plata, Argentina.
María Cecilia
MC
Castro
Cátedra de Farmacología Básica, Facultad de Ciencias Médicas, UNLP and CICPBA, 1900 La Plata, Argentina.
Guillermo
0000-0001-9541-9688
G
Schinella
Instituto Multidisciplinario de Biología Celular (IMBICE), CONICET-CICPBA-UNLP, 1900 La Plata, Argentina.
Daniel
0000-0001-8080-8509
D
Castrogiovanni
Centro de Endocrinología Experimental y Aplicada (CENEXA), UNLP-CONICET-FCM, 1900 La Plata, Argentina.
Eduardo
0000-0002-6556-6051
E
Spinedi
Centro de Endocrinología Experimental y Aplicada (CENEXA), UNLP-CONICET-FCM, 1900 La Plata, Argentina.
María Laura
0000-0003-1184-8704
ML
Massa
Centro de Endocrinología Experimental y Aplicada (CENEXA), UNLP-CONICET-FCM, 1900 La Plata, Argentina.
Flavio
0000-0001-6197-7251
F
Francini