Octanoate inhibits triglyceride synthesis in 3T3-L1 and human adipocytes.
To understand how medium-chain fatty acids (FA) influence lipid metabolism in adipocytes, we studied the effects of octanoate on the oxidation of glucose and endogenous palmitate, cellular O(2) consumption, mitochondrial membrane potential, lipid synthesis from long-chain FA, glucose and lactate. We found that octanoate significantly suppressed the esterification of oleate into triglycerides (TG) in both 3T3-L1 and human adipocytes. Octanoate also significantly suppressed de novo FA synthesis. These effects were associated with octanoate-mediated reductions in the activities of acyl CoA:1,2-diacylglycerol acyltransferase (DGAT) and acetyl CoA carboxylase (ACC). Cells pretreated with octanoate had reduced mRNA levels for a number of lipid metabolism genes, including of DGAT, ACC and stearoyl CoA desaturase-1. On the other hand, octanoate did not acutely perturb cellular O(2) consumption or mitochondrial membrane potential. Together, these results suggest that octanoate affected adipocyte function by reducing TG synthesis but not by enhancing oxidation.
Guo
Wen
W
Obesity Research Center, Department of Biophysics, Boston University School of Medicine, Boston, MA 02118, USA. wguo@bu.edu
Lei
Tianguang
T
Wang
Tong
T
Corkey
Barbara E
BE
Han
Jianrong
J
D016475:3T3 Cells / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000217:Acyltransferases / Q000037:antagonists & inhibitors; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D051048:Diacylglycerol O-Acyltransferase; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004951:Esterification; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000096:biosynthesis; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D014280:Triglycerides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D002210:Caprylates; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D008055:Lipids; D012333:RNA, Messenger; D014280:Triglycerides; D000217:Acyltransferases; C494881:DGAT1 protein, human; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase; D000103:Acetyl-CoA Carboxylase; D005947:Glucose