Effects and Potential Mechanisms of Pioglitazone on Lipid Metabolism in Obese Diabetic KKAy Mice

Figure 6

Schematic diagram for the potential mechanisms of pioglitazone exacerbation of hepatic steatosis and increased plasma cholesterol in KKAy mice. Pioglitazone induced hepatic steatosis may be mediated by (1) increased uptake of FFAs from plasma to liver through promoting FFA transporter (LPL, ap2); (2) enhanced de novo lipogenesis (DNL) in the liver (FAS, ACC, SCD-1); (3) decreased TGs lipolysis and FFAs β-oxidation (HSL, CPT-1a); (4) impaired secretion of lipoprotein (VLDL) into plasma (apoB, MTTP); (5) increased dietary fat absorption. Furthermore, pioglitazone may suppress the clearance of serum cholesterol from the liver predominantly through inhibiting LDL-R and SR-BI expression, thus increasing the plasma levels of cholesterol.