title: Effects of cannabinoid receptor 1 (brain) on lipid accumulation by transcriptional control of CPT1A and CPT1B.
abstract: CB1 (also known as CNR1), a main receptor for cannabinoids acting at PPARs, can enhance fat deposition. Carnitine palmitoyltransferase-1 (CPT1), an enzyme responsible for the transport of long-chain fatty acids for β-oxidation, is closely related to fat deposition. Whether CB1 can regulate intramuscular adipocytes lipid accumulation through regulation of CPT1 is unclear. Based on the investigation of tissue- and breed-specific CPT1A and CPT1B mRNA expression levels in Jinhua and Landrace pigs, we studied the effects of CB1 on lipid accumulation and CPT1B expression by treating porcine intramuscular adipocytes with CB1 antagonist Δ9-THC and antagonist SR141716. Results showed that muscle CPT1 mRNA was expressed at higher levels in the longissimus dorsi and subcutaneous fat. Liver CPT1A mRNA expression levels were higher in the pancreas, duodenum and liver. Compared with Landrace pigs, CPT1A and CPT1B in the longissimus dorsi of Jinhua pigs were significantly higher and positively correlated with intramuscular fat content. However, for subcutaneous fat, CPT1 levels were significantly lower and negatively correlated with body fat percentage. Δ9-THC significantly increased CB1 mRNA levels and lipid accumulation but decreased CPT1A and CPT1B mRNA levels. Conversely, SR141716 reduced CB1 mRNA levels but increased CPT1A and CPT1B mRNA levels, resulting in decreased lipid accumulation. The CPT1 antagonist etomoxir did not affect CB1 expression, suggesting that CB1 is likely upstream of CPT1A and CPT1B. Meanwhile, PPARA expression was greatly decreased when CPT1A and CPT1B were inhibited and enhanced when CPT1A and CPT1B were activated. Taken together, these data indicate that CB1 can affect intramuscular fat deposition by regulating both CPT1A and CPT1B mRNA expression, with the PPARA signal pathway likely playing a major role in this process.
authors.affiliation: Key laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture, Zhejiang Provincial Laboratory of Feed and Animal Nutrition, Institute of Feed Science, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Y-F
authors.initials: YF
authors.lastname: Zhang
authors.forename: Z-Q
authors.initials: ZQ
authors.lastname: Yuan
authors.forename: D-G
authors.initials: DG
authors.lastname: Song
authors.forename: X-H
authors.initials: XH
authors.lastname: Zhou
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Wang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D001947:Breeding; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D013759:Dronabinol; D004852:Epoxy Compounds; D050356:Lipid Metabolism; D008460:Meat; D018482:Muscle, Skeletal / Q000378:metabolism; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D000077285:Rimonabant; D050151:Subcutaneous Fat / Q000378:metabolism; D034421:Sus scrofa / Q000235:genetics*
chemical_list: D004852:Epoxy Compounds; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol; D002334:Carnitine O-Palmitoyltransferase; C054207:etomoxir; D000077285:Rimonabant
keywords: adipocytes; agonist; antagonist; gene expression; lipid deposition