Abstract
Angiopoietin-like protein 8 (ANGPTL8) is an hepatokine altered in several metabolic conditions, such as obesity, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). We sought to explore whether ANGPTL8 is involved in NAFLD amelioration after bariatric surgery in experimental models and patients with severe obesity. Plasma ANGPTL8 was measured in 170 individuals before and 6 months after bariatric surgery. Hepatic ANGPTL8 expression was evaluated in liver biopsies of patients with severe obesity undergoing bariatric surgery with available liver pathology analysis (n = 75), as well as in male Wistar rats with diet-induced obesity subjected to sham operation, sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) (n = 65). The effect of ANGPTL8 on lipogenesis was assessed in human HepG2 hepatocytes under palmitate-induced lipotoxic conditions. Plasma concentrations and hepatic expression of ANGPTL8 were increased in patients with obesity-associated NAFLD in relation to the degree of hepatic steatosis. Sleeve gastrectomy and RYGB improved hepatosteatosis and reduced the hepatic ANGPTL8 expression in the preclinical model of NAFLD. Interestingly, ANGPTL8 inhibited steatosis and expression of lipogenic factors (PPARG2, SREBF1, MOGAT2 and DGAT1) in palmitate-treated human hepatocytes. Together, ANGPTL8 is involved in the resolution of NAFLD after bariatric surgery partially by the inhibition of lipogenesis in steatotic hepatocytes.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and comprises a spectrum of liver disorders ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis [1]
All indices of adiposity (body mass index (BMI), waist circumference, body fat percentage and serum leptin levels) were higher (p < 0.0001) in participants with severe obesity compared with normal-weight controls
We evaluated plasma Angiopoietin-like protein 8 (ANGPTL8) concentrations 6 months after sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB) in patients with obesity and biopsy-proven nonalcoholic fatty liver disease (NAFLD)
Summary
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and comprises a spectrum of liver disorders ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis [1]. The incidence of NAFLD is rising due to the pandemic spread of obesity and type 2 diabetes (T2D). In this regard, the global prevalence of NAFLD in the general population is 24% [2], increasing to 75–90% and. Bariatric surgery has been proposed as a therapeutic option to reduce liver injury in those patients with obesity who have been diagnosed for NAFLD and are unresponsive to lifestyle interventions and pharmacotherapy [7,8]. Sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB), the most commonly used bariatric surgical procedures, appear to be efficacious in the improvement of liver transaminases and histological lesions in patients with obesity and NAFLD [9]. Solid and mechanistic data on the comparative effects of these techniques on NAFLD amelioration are still needed
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