title: Eicosapentaenoic Acid-Enriched Phosphatidylcholine Attenuated Hepatic Steatosis Through Regulation of Cholesterol Metabolism in Rats with Nonalcoholic Fatty Liver Disease.
abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Disturbed cholesterol metabolism plays a crucial role in the development of NAFLD. The present study was conducted to evaluate the effects of EPA-PC extracted from sea cucumber on liver steatosis and cholesterol metabolism in NAFLD. Male Wistar rats were randomly divided into seven groups (normal control group, model group, lovastatin group, low- and high-dose EPA groups, and low- and high-dose EPA-PC groups). Model rats were established by administering a diet containing 1% orotic acid. To determine the possible cholesterol metabolism promoting mechanism of EPA-PC, we analyzed the transcription of key genes and transcriptional factors involved in hepatic cholesterol metabolism. EPA-PC dramatically alleviated hepatic lipid accumulation, reduced the serum TC concentration, and elevated HDLC levels in NAFLD rats. Fecal neutral cholesterol excretion was also promoted by EPA-PC administration. Additionally, EPA-PC decreased the mRNA expression of hydroxymethyl glutaric acid acyl (HMGR) and cholesterol 7α-hydroxylase (CYP7A), and increased the transcription of sterol carrying protein 2 (SCP2). Moreover, EPA-PC stimulated the transcription of peroxisome proliferators-activated receptor α (PPARα) and adenosine monophosphate activated protein kinase (AMPK) as well as its modulators, liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent kinase kinase (CAMKK). Based on the results, the promoting effects of EPA-PC on NAFLD may be partly associated with the suppression of cholesterol synthesis via HMGR inhibition and the enhancement of fecal cholesterol excretion through increased SCP2 transcription. The underlying mechanism may involve stimulation of PPARα and AMPK.
authors.affiliation: College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao, 266003, Shandong Province, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao, 266003, Shandong Province, China.
authors.forename: Di
authors.initials: D
authors.lastname: Shi
authors.affiliation: College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao, 266003, Shandong Province, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Shandong Oriental Ocean Sci-tech Co., Ltd., Yantai, 264003, Shandong Province, China.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao, 266003, Shandong Province, China.
authors.forename: Qiping
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao, 266003, Shandong Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao, 266003, Shandong Province, China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao, 266003, Shandong Province, China. xuechanghuouc@163.com.
authors.forename: Changhu
authors.initials: C
authors.lastname: Xue
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002784:Cholesterol / Q000097:blood*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics; D004195:Disease Models, Animal; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009963:Orotic Acid / Q000009:adverse effects*; D010713:Phosphatidylcholines / Q000737:chemistry*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012616:Sea Cucumbers / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D002352:Carrier Proteins; D010713:Phosphatidylcholines; C072087:sterol carrier proteins; D009963:Orotic Acid; D002784:Cholesterol; D015118:Eicosapentaenoic Acid; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase
keywords: Cholesterol metabolism; Eicosapentaenoic acid-enriched phosphatidylcholine; Hepatic steatosis; Nonalcoholic fatty liver disease