Chronic glucocorticoid-rich milieu and liver dysfunction

VILLAGARCÍA H; SABUGO V; CASTRO MC; SCHINELLA G; CASTROGIOVANNI D; SPINEDI E; MASSA ML; FRANCINI F

International Journal of Endocrinology

Hindawi Publishing Corporation

Año: 2016 p. 1 - 12

We investigated the impact ofchronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG,treatment) on liver oxidative stress (OS), inflammation and, carbohydrate/lipidmetabolism in adult male rats. We evaluated the peripheral concentrations ofseveral metabolic and OS markers, and insulin resistance indexes. In liver weassessed: a) OS (GSH and protein carbonyl groups) and inflammatory (IL-1b, TNFa and PAI-1) biomarkers; and b) carbohydrate and lipid metabolisms. MSGrats displayed: degenerated optic nerves, hypophagia, low body and liverweights, and enlarged adipose tissue mass; higher peripheral levels of glucose,triglycerides, insulin, uric acid, leptin, corticosterone, transaminases andTBARS, 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 andactivity) and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fattyacid synthase and glycerol-3-phosphate (mRNAs) were increased. In conclusionadult MSG rats developed an insulin-resistant state and increased OS, and serioushepatic dysfunction characterized by inflammation and metabolic signssuggesting increased lipogenesis. These features, shared by both Metabolic andCushing?s syndrome human phenotypes, support that a chronic glucocorticoid-richendogenous environment mainly impacts on hepatic glucose cycle, displacinglocal metabolism to lipogenesis. Whether correcting the glucocorticoid-richenvironment ameliorates such dysfunctions requires further investigation.