A conjugated fatty acid present at high levels in bitter melon seed favorably affects lipid metabolism in hepatocytes by increasing NAD(+)/NADH ratio and activating PPARα, AMPK and SIRT1 signaling pathway.
α-Eleostearic acid (α-ESA), or the cis-9, trans-11, trans-13 isomer of conjugated linolenic acid, is a special fatty acid present at high levels in bitter melon seed oil. The aim of this study was to examine the effect of α-ESA on hepatic lipid metabolism. Using H4IIEC3 hepatoma cell line, we showed that α-ESA significantly lowered intracellular triglyceride accumulation compared to α-linolenic acid (LN), used as a fatty acid control, in a dose- and time-dependent manner. The effects of α-ESA on enzyme activities and mRNA profiles in H4IIEC3 cells suggested that enhanced fatty acid oxidation and lowered lipogenesis were involved in α-ESA-mediated triglyceride lowering effects. In addition, α-ESA triggered AMP-activated protein kinase (AMPK) activation without altering sirtuin 1 (SIRT1) protein levels. When cells were treated with vehicle control (VC), LN alone (LN; 100μmol/L) or in combination with α-ESA (LN+α-ESA; 75+25μmol/L) for 24h, acetylation of forkhead box protein O1 was decreased, while the NAD(+)/NADH ratio, mRNA levels of NAMPT and PTGR1 and enzyme activity of nicotinamide phosphoribosyltransferase were increased by LN+α-ESA treatment compared to treatment with LN alone, suggesting that α-ESA activates SIRT1 by increasing NAD(+) synthesis and NAD(P)H consumption. The antisteatosis effect of α-ESA was confirmed in mice treated with a high-sucrose diet supplemented with 1% α-ESA for 5weeks. We conclude that α-ESA favorably affects hepatic lipid metabolism by increasing cellular NAD(+)/NADH ratio and activating PPARα, AMPK and SIRT1 signaling pathways.
Department of Nutrition, China Medical University, Taichung, Taiwan.
Gou-Chun
GC
Chen
Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan.
Hui-Min
HM
Su
Department of Nutrition, China Medical University, Taichung, Taiwan.
Yu-Shun
YS
Lin
Department of Nutrition, China Medical University, Taichung, Taiwan.
Po-Yen
PY
Tsou
Hualien District Agricultural Research and Extension Station, Hualien, Taiwan.
Jong-Ho
JH
Chyuan
Department of Nutrition, China Medical University, Taichung, Taiwan. Electronic address: pmchao@mail.cmu.edu.tw.
Pei-Min
PM
Chao
D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D019587:Dietary Supplements; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism*; D015228:Hypertriglyceridemia / Q000097:blood / Q000378:metabolism / Q000517:prevention & control; D000960:Hypolipidemic Agents / Q000378:metabolism / Q000627:therapeutic use*; D044243:Linoleic Acids, Conjugated / Q000378:metabolism / Q000627:therapeutic use*; D008042:Linolenic Acids / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D008810:Mice, Inbred C57BL; D029777:Momordica charantia / Q000737:chemistry; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism; D051381:Rats; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000960:Hypolipidemic Agents; D044243:Linoleic Acids, Conjugated; D008042:Linolenic Acids; D047493:PPAR alpha; D009243:NAD; C004934:eleostearic acid; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
AMP-activated protein kinase; H4IIEC3 cells; Nicotinamide phosphoribosyltransferase; PPARα; Sirtuin-1; α-Eleostearic acid