The loss of hepatic PPAR α promotes inflammation and serum hyperlipidemia in diet-induced obesity.

The loss of hepatic PPARα promotes inflammation and serum hyperlipidemia in diet-induced obesity. Am J Physiol Regul Integr Comp Physiol. 2019 Sep 04;: Authors: Stec DE, Gordon DM, Hipp JA, Hong S, Mitchell ZL, Franco NR, Robison JW, Anderson CD, Stec DF, Hinds TD Abstract Agonists for PPARα are used clinically to reduce triglycerides and improve high-density lipoprotein (HDL) cholesterol levels in patients with hyperlipidemia. Whether the mechanism of PPARα activation to lower serum lipids occurs in the liver or other tissues is unknown. To determine the function of hepatic PPARα on lipid profiles in diet-induced obese mice, we placed hepatocyte-specific PPARα knockout (PparaHepKO) and wild-type (Pparafl/fl) mice on a high-fat diet (HFD) or normal fat diet (NFD) for 12 weeks. There was no significant difference in weight gain, percent body fat mass, or percent body lean mass between the groups of mice in response to HFD or NFD. Interestingly, the PparaHepKO mice on HFD had worsened hepatic inflammation and a significant shift in the pro-inflammatory M1 macrophage population. These changes were associated with higher hepatic fat mass and decreased hepatic lean mass in the PparαHepKO on HFD, but not in NFD, as measured by Oil Red O and non-invasive EchoMRI analysis (31.1+ 2.8 vs. 20.2 + 1.5, 66.6 + 2.5 vs. 76.4 + 1.5 %, P<0.05). We did find that this was related to significantly reduced peroxisomal gene function and lower pla...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research