Depletion of B cell-activating factor attenuates hepatic fat accumulation in a murine model of nonalcoholic fatty liver disease

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Obesity-induced adipose-tissue dysfunction is a critical contributor to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). B cell-activating factor (BAFF) is an adipokine related to impaired insulin sensitivity, and the serum BAFF concentration is associated with NAFLD severity. In this study, we aimed to determine the direct in vivo role of BAFF in the development of insulin resistance, adipocyte dysfunction, and hepatic steatosis using BAFF -/- mice fed a high-fat diet (HFD). HFD-fed BAFF -/- mice exhibited significantly improved insulin sensitivity despite their increased weight gain and adiposity relative to HFD-fed wild-type mice. Moreover, inflammation, especially the accumulation of CD11c + adipose-tissue macrophages, and fibrosis of epididymal adipose tissue were reduced, contributing to healthy adipose-tissue expansion in obese BAFF -/- mice. In line with metabolically healthy obesity, hepatic steatosis also decreased, and we observed attenuated de novo lipogenesis in both the livers and hepatocytes of BAFF -/- mice. Our data revealed that BAFF serves as a potential stimulator of unhealthy adipose-tissue expansion by triggering inflammation and fibrosis and ultimately leading to enhanced insulin resistance and NAFLD. Therefore, these results suggest that BAFF is a promising target for diabetes and NAFLD treatment.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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