Details

Autor(en) / Beteiligte

• Gao, Qian
• Jia, Yuzhi
• Yang, Gongshe
• Zhang, Xiaohong
• Boddu, Prajwal C
• Petersen, Bryon
• Narsingam, Saiprasad
• Zhu, Yi-Jun
• Thimmapaya, Bayar
• Kanwar, Yashpal S
• Reddy, Janardan K

Titel

PPARα-Deficient ob/ob Obese Mice Become More Obese and Manifest Severe Hepatic Steatosis Due to Decreased Fatty Acid Oxidation

Ist Teil von

• The American journal of pathology, 2015-05, Vol.185 (5), p.1396-1408

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 α (PPARα) 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 PPARα-regulated hepatic FAO and energy burning in the progression of fatty liver disease, we generated PPARα-deficient ob/ob (PPARαΔ 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 PPARαΔ ob/ob mice as they fail to up-regulate FAO systems. PPARαΔ ob/ob mice also do not respond to peroxisome proliferative and mitogenic effects of PPARα agonist Wy-14,643. Although PPARαΔ 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 PPARα activation–related increase in FAO in fatty livers of obese ob/ob mice increases liver cancer risk, whereas deletion of PPARα 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.