IFN-α-2b treatment protects against diet-induced obesity and alleviates non-alcoholic fatty liver disease in mice.

Autor: Quiroga AD; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina; CAECIHS, Universidad Abierta Interamericana, Rosario, Argentina. Electronic address: quiroga@ifise-conicet.gov.ar., Comanzo CG; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: comanzo@ifise-conicet.gov.ar., Heit Barbini FJ; CAECIHS, Universidad Abierta Interamericana, Rosario, Argentina., Lucci A; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina. Electronic address: lucci@ifise-conicet.gov.ar., Vera MC; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: vera@ifise-conicet.gov.ar., Lorenzetti F; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: lorenzetti@ifise-conicet.gov.ar., Ferretti AC; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina. Electronic address: ferretti@ifise-conicet.gov.ar., Ceballos MP; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: ceballos@ifise-conicet.gov.ar., Alvarez ML; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina; CAECIHS, Universidad Abierta Interamericana, Rosario, Argentina. Electronic address: alvarez@ifise-conicet.gov.ar., Carrillo MC; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina. Electronic address: carrillo@ifise-conicet.gov.ar.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2019 Sep 15; Vol. 379, pp. 114650. Date of Electronic Publication: 2019 Jul 09.
DOI: 10.1016/j.taap.2019.114650
Abstrakt: IFN-α is used for inflammatory purposes, and obesity and NAFLD are strongly correlated with inflammatory processes. We wondered whether IFN-α-2b can attenuate obesity development and its associated NAFLD in mice fed high fat diet (HFD) for 10 weeks. IFN-α-2b had a robust effect on body weight loss associated with NAFLD amelioration by decreasing hepatic inflammation. IFN-α-2b-treated mice showed increased plasma cholesterol levels together with decreased hepatic cholesterol, both on chow and HF diets. Interestingly, mice on IFN-α-2b treatment secreted smaller VLDL particles highly enriched in cholesterol. Mechanistically, we found that IFN-α-2b antiobesity effects were related to increased fatty acid oxidation; and its effects on cholesterol metabolism were due to both a decrease in the master cholesterogenic transcription factor SREBP-2 and in the rate limiting enzyme in cholesterol synthesis, HMGCR. To our knowledge, this is the first report showing the effects of IFN-α-2b on the prevention of the development of HFD-induced body weight gain and dyslipidemia through a mechanism that involves fatty acid oxidation and cholesterol decrease. These studies comprise necessary steps for understanding the amelioration of obesity and NAFLD. Results shed some light into the mechanism of action of natural cytokines, and their effects on ameliorating obesity and its related diseases.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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