title: Alleviative effect of ciliary neurotrophic factor analogue on high fat-induced hepatic steatosis is partially independent of the central regulation.
abstract: Ciliary neurotrophic factor (CNTF) analogues were reported to ameliorate fatty liver in db/db or high-fat diet-fed mice. It is generally thought that CNTF exerts its actions centrally. The aim of this study was to investigate whether peripheral effects of CNTF analogues are involved in the therapeutic effect on high fat-induced hepatic steatosis. The rat model of fatty liver was induced by a high-fat diet (HFD) for 12 weeks. In the next 2 weeks, rats were fed the HFD along with subcutaneous injection of vehicle or mutant recombinant human CNTF (rhmCNTF 0.05-0.2 mg/kg per day). Steatotic HepG2 cells were induced by 50% fetal bovine serum (FBS) for 48 hours, and then treated with rhmCNTF for 24 hours. The results showed that after rhmCNTF treatment, hepatic triglyceride (TG) accumulation was attenuated both in vivo and in vitro. RhmCNTF increased protein expression of CPT-1 and PPARα, and decreased SREBP-1c, FAS and SCD-1 in steatotic HepG2 cells. But the production of nitric oxide and 8-isoPGF2αin steatotic HepG2 cells was not affected by rhmCNTF. These results suggest that rhmCNTF has a peripheral effect that alleviates fat-induced hepatic steatosis.
authors.affiliation: Institute of Pharmacology, School of Basic Medical Science, Lanzhou University, Lanzhou, China.|Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou, China.
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Cui
authors.affiliation: Institute of Pharmacology, School of Basic Medical Science, Lanzhou University, Lanzhou, China.|Gansu Provincial Second People's Hospital, Lanzhou, China.
authors.forename: Li-Ning
authors.initials: LN
authors.lastname: Yang
authors.affiliation: Institute of Pharmacology, School of Basic Medical Science, Lanzhou University, Lanzhou, China.|Shihua General Hospital of Lanzhou, Lanzhou, China.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Institute of Pharmacology, School of Basic Medical Science, Lanzhou University, Lanzhou, China.|Gansu Provincial Hospital, Lanzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Pharmacology, School of Basic Medical Science, Lanzhou University, Lanzhou, China.|Qinhai University, Xining, China.
authors.forename: Rui-Lian
authors.initials: RL
authors.lastname: Li
authors.affiliation: Dingxi District of Gansu University of Chinese Medicine, Dingxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Institute of Pharmacology, School of Basic Medical Science, Lanzhou University, Lanzhou, China.|Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou, China.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Wu
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D059305:Diet, High-Fat / Q000009:adverse effects*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D014280:Triglycerides / Q000378:metabolism
chemical_list: D020934:Ciliary Neurotrophic Factor; D011994:Recombinant Proteins; D014280:Triglycerides; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost
keywords: HepG2 cell; ciliary neurotrophic factor; high-fat diet; non-alcoholic fatty liver diseases; rat