| First Author | Gao Q | Year | 2015 |
| Journal | Am J Pathol | Volume | 185 |
| Issue | 5 | Pages | 1396-408 |
| PubMed ID | 25773177 | Mgi Jnum | J:220678 |
| Mgi Id | MGI:5635933 | Doi | 10.1016/j.ajpath.2015.01.018 |
| Citation | Gao Q, et al. (2015) PPARalpha-Deficient ob/ob Obese Mice Become More Obese and Manifest Severe Hepatic Steatosis Due to Decreased Fatty Acid Oxidation. Am J Pathol 185(5):1396-408 |
| abstractText | Obesity poses an increased risk of developing metabolic syndrome and closely associated nonalcoholic fatty liver disease, including liver cancer. Satiety hormone leptin-deficient (ob/ob) mice, considered paradigmatic of nutritional obesity, develop hepatic steatosis but are less prone to developing liver tumors. Sustained activation of peroxisome proliferator-activated receptor alpha (PPARalpha) in ob/ob mouse liver increases fatty acid oxidation (FAO), which contributes to attenuation of obesity but enhances liver cancer risk. To further evaluate the role of PPARalpha-regulated hepatic FAO and energy burning in the progression of fatty liver disease, we generated PPARalpha-deficient ob/ob (PPARalpha(Delta)ob/ob) mice. These mice become strikingly more obese compared to ob/ob littermates, with increased white and brown adipose tissue content and severe hepatic steatosis. Hepatic steatosis becomes more severe in fasted PPARalpha(Delta)ob/ob mice as they fail to up-regulate FAO systems. PPARalpha(Delta)ob/ob mice also do not respond to peroxisome proliferative and mitogenic effects of PPARalpha agonist Wy-14,643. Although PPARalpha(Delta)ob/ob mice are severely obese, there was no significant increase in liver tumor incidence, even when maintained on a diet containing Wy-14,643. We conclude that sustained PPARalpha activation-related increase in FAO in fatty livers of obese ob/ob mice increases liver cancer risk, whereas deletion of PPARalpha in ob/ob mice aggravates obesity and hepatic steatosis. However, it does not lead to liver tumor development because of reduction in FAO and energy burning. |
