{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gao Q"],"funding":["China Scholarship Council","NIDDK NIH HHS","NCI NIH HHS","National Institutes of Health","PHS HHS"],"pagination":["1396-408"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4419205"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["185(5)"],"pubmed_abstract":["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 (PPARα(Δ)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 PPARα(Δ)ob/ob mice as they fail to up-regulate FAO systems. PPARα(Δ)ob/ob mice also do not respond to peroxisome proliferative and mitogenic effects of PPARα agonist Wy-14,643. Although PPARα(Δ)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."],"journal":["The American journal of pathology"],"pubmed_title":["PPARα-Deficient ob/ob Obese Mice Become More Obese and Manifest Severe Hepatic Steatosis Due to Decreased Fatty Acid Oxidation."],"pmcid":["PMC4419205"],"funding_grant_id":["DK60015","R01 DK060635","DK60635","R56 DK058614","DK58614","R01 DK083163","R01 DK058614","DK097240","R01 DK097249","R21A1094296","DK083163","CSC 2011630169","R56 DK083163","P30 CA060553"],"pubmed_authors":["Gao Q","Yang G","Narsingam S","Zhang X","Boddu PC","Thimmapaya B","Jia Y","Reddy JK","Zhu YJ","Kanwar YS","Petersen B"],"additional_accession":[]},"is_claimable":false,"name":"PPARα-Deficient ob/ob Obese Mice Become More Obese and Manifest Severe Hepatic Steatosis Due to Decreased Fatty Acid Oxidation.","description":"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 (PPARα(Δ)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 PPARα(Δ)ob/ob mice as they fail to up-regulate FAO systems. PPARα(Δ)ob/ob mice also do not respond to peroxisome proliferative and mitogenic effects of PPARα agonist Wy-14,643. Although PPARα(Δ)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.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 May","modification":"2024-11-07T09:16:22.176Z","creation":"2019-03-27T01:50:56Z"},"accession":"S-EPMC4419205","cross_references":{"pubmed":["25773177"],"doi":["10.1016/j.ajpath.2015.01.018"]}}