Beneficial Effects on Hepatic Steatosis in a Murine Obesity Model after IL-1 Type Cytokine Inactivation

Background: IL-1α/β plays a crucial role in the development of NAFLD, a common cause for chronic liver disease. We want to assess the suitability of cytokine intervention as a therapeutic target for NAFLD and clarify pathophysiological effects of IL-1.

Methods: C57BL6-mice were subcutaneously vaccinated with virus-like particles presenting IL-1α/β-antigens, fed a high-fat/high-sucrose diet (HFSD) at w14 and sacrificed at w20. Robust antibody responses were assessed by ELISA, triglyceride levels measured by TG-assay and frozen liver sections stained with H&E/SudanIII to gauge fat accumulation. Expression patterns of genes of interest are analysed on RNA and protein level.

Results: Mice vaccinated against IL-1α/β before HFSD displayed a significant reduction of visceral fat versus controls. Liver tissue analysis showed hepatic steatosis with significant reduction of lipid accumulation and major effects in the combination group. Expression of IL-1 signalling molecules was reduced while lipogenic enzyme expression was down-regulated. Significant reduction of inflammatory cytokine production in adipose tissue could contribute to improved liver health in IL-1α/β depleted mice.

Conclusion: Our HFSD-model study indicates that biological inactivation of IL-1a/β affects weight gain, augmentation of visceral adipose tissue and hepatic lipid accumulation early in the course of NAFLD thereby exerting further favourable metabolic effects beyond inflammation and fibrogenesis. Our data further highlight the role of IL-1 in the disease's pathogenesis and support further studies in clinical application.