Weight Loss Induced by Bariatric Surgery Restricts Hepatic GDF15 Expression

Abstract

Introduction. Obesity and related nonalcoholic fatty liver disease (NAFLD) are an emerging health care issue that imposes substantial morbidity to individuals. Growth and differentiation factor 15 (GDF15) limits food uptake, body weight, and energy balance by modulation of GDNF-family receptor α-like (GFRAL) signalling in the hindbrain. However, the regulation of GDF15 expression in obesity and NAFLD is incompletely understood. We sought to define the impact of weight loss achieved by laparoscopic adjustable gastric banding (LAGB) on hepatic and adipose GDF15 expression in a cohort of severely obese patients. Methods. We analysed GDF15 expression of liver and subcutaneous adipose tissue before and 6 months after LAGB in severely obese patients undergoing LAGB by quantitative real-time PCR. To assess the role of inflammation on GDF15 expression, we analysed Hep G2 hepatocytes stimulated with cytokines such as IL-1β, TNFα, IL-6, LPS, or cellular stressors such as tunicamycin. Results. GDF15 expression was mostly confined to the liver compared to adipose tissue in severely obese patients. Weight loss induced by LAGB was associated with reduced hepatic (but not adipose tissue) expression of GDF15. Stimulation with IL-1β or tunicamycin induced hepatic GDF15 expression in hepatocytes. In line with this, hepatic GDF15 expression directly correlated with IL-1β expression and steatosis severity in NAFLD. These data demonstrated that amelioration of metabolic inflammation and weight loss reduced hepatic GDF15 expression. Conclusion. Based on recent mechanistic findings, our data suggest that hepatic GDF15 may serve as a negative feedback mechanism to control energy balance in NAFLD.