title: 5-HT 2 receptor mediates high-fat diet-induced hepatic steatosis and very low density lipoprotein overproduction in rats.
abstract: 5-HT has been shown to mediate abnormality of hepatic lipid metabolism through activation of mammalian target of rapamycin (mTOR). However, it is unclear whether 5-HT is directly involved in high-fat diet (HFD)-induced hepatic steatosis.
  
  
  
  Male rats were allocated into seven groups with control, either HFD feeding, 5-HT treatment, or HFD feeding and 5-HT treatment with or without sarpogrelate treatment, all of which were executed for 4 weeks. HepG2 cells were exposed to 5-HT or palmitic acid (PA) with or without rapamycin or Sar treatment.
  
  
  
  Rats fed with HFD or exposed to 5-HT led to abnormalities with activated hepatic mTOR-S6K pathway, overproduction of hepatic triglycerides and VLDL with steatosis, and hyperlipidemia, which were exacerbated by a combination of HFD and 5-HT. Sarpogrelate significantly inhibited above abnormalities induced by HFD and 5-HT, alone or in a combination. Additionally, HFD caused up-regulation of 5-HT2 receptors (5-HT2R), including 5-HT2AR and 5-HT2BR, and 5-HT synthesis in the liver, without obvious influence on other 5-HT receptors gene expression. In HepG2 cells, both PA and 5-HT induced overproduction of triglycerides and VLDL with lipid droplets, and PA up-regulated 5-HT2AR and 5-HT2BR expression and 5-HT synthesis as well. Rapamycin fully abolished PA or 5-HT-induced mTOR activation, which was more effective than sarpogrelate. However, the inhibitory effects of rapamycin on PA or 5-HT-induced overproduction of triglycerides and VLDL were less than sarpogrelate.
  
  
  
  Up-regulation of hepatic 5-HT2R and 5-HT synthesis by HFD is crucial for HFD-induced overproduction of hepatic triglycerides and VLDL with hyperlipidemia.
authors.affiliation: Postgraduates of China Pharmaceutical University, Nanjing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Postgraduates of China Pharmaceutical University, Nanjing, China.
authors.forename: Keke
authors.initials: K
authors.lastname: Guo
authors.affiliation: Postgraduates of China Pharmaceutical University, Nanjing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Postgraduates of China Pharmaceutical University, Nanjing, China.
authors.forename: Shaoxin
authors.initials: S
authors.lastname: Ma
authors.affiliation: Postgraduates of China Pharmaceutical University, Nanjing, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: An
authors.affiliation: Postgraduates of China Pharmaceutical University, Nanjing, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Undergraduates of China Pharmaceutical University, Nanjing, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Di
authors.affiliation: Undergraduates of China Pharmaceutical University, Nanjing, China.
authors.forename: Siyu
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Physiology, China Pharmaceutical University, Nanjing, China. Electronic address: jihua_fu@cpu.edu.cn.
authors.forename: Jihua
authors.initials: J
authors.lastname: Fu
mesh_terms: D000818:Animals; D015243:Cholesterol, VLDL / Q000096:biosynthesis* / Q000097:blood; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000097:blood / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000096:biosynthesis* / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015243:Cholesterol, VLDL; D008079:Lipoproteins, VLDL; D044348:Receptors, Serotonin, 5-HT2
keywords: 5-HT 2 receptor; 5-HT synthesis; Hepatic lipid abnormality; Mammalian target of rapamycin