Premium
Circadian regulator PER2 plays a critical role in regulating fat metabolism and the development of fatty liver disease
Author(s) -
Pope Brittny A,
Menio Jade,
Deng Jian,
Wheeler Michael D
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.926.4
Subject(s) - endocrinology , per2 , medicine , fatty liver , lipid metabolism , biology , knockout mouse , nonalcoholic fatty liver disease , choline , lipogenesis , triglyceride , metabolism , circadian rhythm , clock , cholesterol , circadian clock , receptor , disease
Recent reports suggest the circadian controlled genes influence key metabolic regulators. Thus, we hypothesize that deletion of the circadian regulator PER2 alters hepatic lipid metabolism in a model of fatty liver disease. C57B6/J wild type and PER2 (−/−) knockout mice were treated with choline sufficient and choline deficient diets, a unique model that causes lipid accumulation in liver. After 6 weeks liver and serum were harvested. Choline deficient diet induced significant liver lipid accumulation as reflected in H&E stained liver sections, and this increase was significantly blunted in PER2 (−/−) mice on choline deficient diet. Liver weight, liver to body weight ratios, and liver triglyceride levels also reflected this observation. Importantly, mRNA for genes involved in hepatic metabolism such as PPARƒÑ, HNF4, FOXa1 and SIRT1 were measured by real time PCR. In PER2−/− mice, PPARƒÑ and SIRT1 expression was significantly elevated in both choline sufficient and deficient diets compared to wildtype mice. Additionally, the increase in TNFƒÑ and £^IFN expression in wildtype mice fed choline deficient diet was significantly blunted in PER2−/− mice. In conclusion, these data suggest that PER2 plays a critical role in fatty acid metabolism and the development of fatty liver disease. Grant Funding Source : Internal