Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity

Figures

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  Figure 1. Effect of insulin resistance and NAFLD on plasma concentrations of ANGPTL8 in patients with severe obesity before and after bariatric surgery. Fasting plasma concentrations of ANGPTL8 according to severe obesity and insulin resistance (a) or hepatic function (b). Impact of weight loss achieved 6 months after sleeve gastrectomy (c) or RYGB (d) in plasma ANGPTL8 levels. Statistical differences were analyzed by one-way ANOVA followed by a Tukey’s test or by a two-tailed paired Student’s t-test, where appropriate. * p < 0.05; ** p < 0.01; *** p < 0.001 vs. patients with NG or normal liver.

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  Figure 2. Hepatic ANGPTL8 expression in obesity-associated T2D and NAFLD. Liver sections obtained from patients with severe obesity classified according to their degree of insulin resistance (a) or hepatic function (b) stained with H-E (upper panels) and marked with antibodies against ANGPTL8 (lower panels) (magnification 200×). Bar graphs show the effect of insulin resistance (c), NAFLD (d) and the degree of liver steatosis (e) on hepatic ANGPTL8 transcripts. (f) Correlation between hepatic ANGPTL8 mRNA and NAS score. Statistical differences were analyzed by one-way ANOVA followed by a Tukey’s test. * p < 0.05 vs. patients with NG, normal liver or 0–5% liver steatosis.

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  Figure 3. Hepatic expression of ANGPTL8 in rats with diet-induced obesity before and after bariatric surgery. Bar graphs show the effect of diet-induced obesity and weight loss achieved 1 month after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) on rat liver weight (a,g), AST (b,h) and ALT (c,i) transaminase levels, intrahepatic TG content (d,j) and hepatic Angptl8 transcript levels (e,k). (f) Liver sections stained with H-E (upper panels) and marked with antibodies against ANGPTL8 (lower panels) (magnification 200x). (l) Correlation between post-surgical hepatic mRNA expression of ANGGPTL8 and intrahepatic TG. Statistical differences were analyzed by a Student’s t-test or one-way ANOVA followed by a Tukey’s test, where appropriate. * p < 0.05, ** p < 0.01 and *** p < 0.001 vs. rats fed a ND or sham-operated groups.

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  Figure 4. ANGPTL8 reversed palmitate-induced lipogenesis in human HepG2 hepatocytes. Bar graphs show the (a) intracellular triacylglycerol content and (b) mRNA expression of lipogenic transcription factors and enzymes in HepG2 hepatocytes stimulated with palmitate in the absence or presence of ANGPTL8 for 24 h. Proliferation rate (c) and transcript levels of hepatocyte differentiation transcription factor HNF4A (d) are shown. Statistical differences were analyzed by a two-way ANOVA or a one-way ANOVA followed by Tukey’s post hoc test, if an interaction between factors was detected. * p < 0.05; *** p < 0.001 vs. unstimulated HepG2 cells; † p < 0.05; †† p < 0.01 vs. palmitate-treated HepG2 cells; a p < 0.05 effect of palmitate; b p < 0.05 effect of ANGPTL8.