Interferon-alpha inhibits adipogenesis via regulation of JAK/STAT1 signaling

Background information: Adipose tissue regulates energy metabolism by means of adipocyte hypertrophy and/or the differentiation of pre-existing adipocytes. Excessive production of some cytokines in adipose tissue is known to be a negative regulator of adipocyte differentiation, and the resulting impaired adipogenesis contributes to disorders like insulin resistance. IFN-alpha is a key immunoregulatory cytokine in the development of type 1 diabetes, lipid disorders and insulin resistance; however, its effect on adipogenesis remains unknown. Method: We examined the effect of IFN-alpha on adipocyte differentiation and its mechanisms. The effect of IFN-alpha on adipogenesis was evaluated by Western blotting, ciRT-PCR, flow cytometric analysis and Oil Red O staining. We also investigated the role of STAT1 in adipogenesis using gene silencing analysis. Results: IFN-alpha inhibited the accumulation of lipid droplets and the expression of adipogenesis related genes. The inhibition of adipocyte differentiation by IFN-alpha occurred in the early stages of differentiation. IFN-alpha arrested the cell cycle at the G(0)/G(1) phase and regulated the expression of CDK2 and p21. These results were confirmed in MEF cells. Treatment with IFN-alpha increased STAT1 phosphotylation, and STAT1 siRNA or inhibitor prevented IFN-a from inhibiting the expression of PPAR gamma and C/EBP alpha as well as cell cycle progression in 3T3-L1 cells. Conclusion: We suggest that IFN-alpha inhibits adipocyte differentiation during the early stage of adipogenesis by regulating the expression of PPAR gamma and C/EBP alpha as well as the cell cycle through JAK/STAT1 signaling pathways. General significance: Our study provides new insights into possible mechanisms of the anti-adipogenetic effects of IFN-alpha. (C) 2016 Elsevier B.V. All rights reserved.