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

HEIT BARBINI, FRANCISCO J.; LORENZETTI, FLORENCIA; ALVAREZ, MARÍA DE L.; COMANZO, CARLA G.; VERA, MARINA C.; CEBALLOS, MARÍA P.; QUIROGA, ARIEL D.; LUCCI, ALVARO; FERRETTI, ANABELA C.; CARRILLO, MARÍA C.; HEIT BARBINI, FRANCISCO J.; LORENZETTI, FLORENCIA; ALVAREZ, MARÍA DE L.; COMANZO, CARLA G.; VERA, MARINA C.; CEBALLOS, MARÍA P.; QUIROGA, ARIEL D.; LUCCI, ALVARO; FERRETTI, ANABELA C.; CARRILLO, MARÍA C.

TOXICOLOGY AND APPLIED PHARMACOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2019 vol. 379

0041-008X

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.