The Mechanism of Increased Intestinal Palmitic Acids Absorption and The Impact On Hepatic Stellate Cell Activation in Non-Alcoholic Steatohepatitis

Abstract Dietary palmitic acids (PAs) promote liver fibrosis in patients with non-alcoholic steatohepatitis (NASH). This study aimed to clarify the intestinal absorption kinetics of dietary PAs and the effect of trans-portal PAs on the activation of hepatic stellate cells (HSCs) involved in liver fibrosis in patients with NASH. First, we found that the concentration of blood PAs after meals was significantly increased in NASH patients compared to control patients (P < 0.01). Second, gene expressions associated with fat absorption and chylomicron formation, such as CD36 and MTP, were significantly increased in the intestine of the NASH model rats fed a high-fat-cholesterol diet compared to control rats. Furthermore, portal PA levels after meals in the NASH model rats were significantly higher compared to control and non-alcoholic fatty liver (NAFL) rats (P<0.01). Third, PA injection via the portal vein to the liver in control rats increased the mRNA levels associated with the activation of HSCs and the expression of α-SMA in liver tissues. Our study showed an increased intestinal absorption of dietary-derived PA in NASH. The rapid increase in PAs via the portal vein to the liver may activate HSCs and affect the development of liver fibrosis in NASH.