Hepatic peroxisome proliferator-activated receptor alpha mediates the major metabolic effects of Wy-14643

被引：21
|
作者：
Li, Guolin [1 ,2 ,3 ,4 ]
Brocker, Chad N. [1 ]
Xie, Cen [1 ]
Yan, Tingting [1 ]
Noguchi, Audrey
Krausz, Kristopher W. [1 ]
Xiang, Rong [5 ,6 ]
Gonzalez, Frank J. [1 ]
机构：
[1] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[2] NHLBI, Murine Phenotyping Core, NIH, Bldg 10, Bethesda, MD 20892 USA
[3] Hunan Normal Univ, Coll Life Sci, Lab Aging Biochem, Changsha 410081, Hunan, Peoples R China
[4] Hunan Normal Univ, Coll Life Sci, Minist Educ, Key Lab Prot Chem & Dev Biol, Changsha, Hunan, Peoples R China
[5] Cent S Univ, State Key Lab Med Genet, Changsha, Hunan, Peoples R China
[6] Cent S Univ, Sch Life Sci, Changsha, Hunan, Peoples R China
来源：
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY | 2018年 / 33卷 / 05期
基金：
美国国家卫生研究院;
关键词：
fibrate drugs; hypolipidemia; hypophagia; PPAR; Wy-14643; PPAR-ALPHA; ENERGY-EXPENDITURE; BODY-WEIGHT; FOOD-INTAKE; EXPRESSION; AGONIST; MOUSE; MICE; HOMEOSTASIS; STEATOSIS;
D O I：
10.1111/jgh.14046
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
Background and AimPeroxisome proliferator-activated receptor alpha (PPAR) is a molecular target of various fibrate drugs clinically used to lower serum lipids. However, the tissue-specific functions of PPAR remain to be elucidated. This study aimed to explore the tissue-specific functions of PPAR in response to Wy-14643. MethodsA hepatocyte-specific Ppara knockout mouse line was used to explore the impact of hepatic PPAR activity on the systemic response to treatment with the potent PPAR agonist Wy-14643. ResultsWy-14643 mainly activated hepatic PPAR and regulated the expression of PPAR target genes in liver. Hepatic Ppara disruption abolished the triglyceride lowering effects of Wy-14643, prevented agonist-induced hypophagia, and ablated PPAR target gene response in the liver. ConclusionsThese findings indicate that Wy-14643 treatment mainly activates hepatic PPAR, and the hypolipidemic and hypophagic effects of Wy-14643 are dependent on PPAR activation within hepatocytes.
引用
收藏
页码：1138 / 1145
页数：8
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