N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats

VILLAGARCIA HG; CASTRO MC; GONZÁLEZ ARBELÁEZ LF; SCHINELLA GR; SPINEDI, E; FRANCINI F

LIFE SCIENCES

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2018 vol. 199 p. 88 - 95

0024-3205

Aim: Hypothalamic obese rats are characterized by pre-diabetes, dyslipidemia, hyperadiposity, inflammationand, liver dysmetabolism with oxidative stress (OS), among others. We studied endocrine-metabolic dysfunctionsand, liver OS and inflammation in both monosodium L-glutamate (MSG)-neonatally damaged and controllitter-mate (C) adult male rats, either chronically treated with N-Acetyl-L-Cysteine since weaned (C-NAC andMSG-NAC) or not.Methodology: We evaluated circulating TBARS, glucose, insulin, triglycerides, uric acid (UA) and, aspartate andalanine amino-transferase; insulin sensitivity markers (HOMA indexes, Liver Index of Insulin Sensitivity ?LISI-)were calculated and liver steps of the insulin-signaling pathway were investigated. Additionally, we monitoredliver OS (protein carbonyl groups, GSH and iNOS level) and inflammation-related markers (COX-2 and TNFαprotein content; gene expression level of Il1b, Tnfα and Pai-1); and carbohydrate and lipid metabolic functions(glucokinase/fructokinase activities and, mRNA levels of Srebp1c, Fas and Gpat).Key Findings: Chronic NAC treatment in MSG rats efficiently decreased the high circulating levels of triglycerides,UA, transaminases and TBARS, as well as peripheral (high insulinemia and HOMA indexes) and liver (LISIand the P-AKT:AKT and P-eNOS:eNOS protein ratio values) insulin-resistance. Moreover, NAC therapy in MSGrats prevented liver dysmetabolism by decreasing local levels of OS and inflammation markers. Finally, NACtreatedMSG rats retained normal liver glucokinase and fructokinase activities, and Srebp1c, Fas and Gpat (lipogenicgenes) expression levels.Significance: Our study strongly supports that chronic oral antioxidant therapy (NAC administration) preventedthe development of pre-diabetes, dyslipidemia, and inflamed-dysmetabolic liver in hypothalamic obese rats byefficiently decreasing high endogenous OS.