Novel acyl-coenzyme A:monoacylglycerol acyltransferase plays an important role in hepatic triacylglycerol secretion.
Acyl-CoA:monoacylglycerol acyltransferase (MGAT) plays a predominant role in the resynthesis of triacylglycerol in the small intestine, but its contribution to triacylglycerol synthesis in other tissues, such as the liver, is not clear. In this study, we identified a novel MGAT gene, which is identical with lysophosphatidylglycerol acyltransferase1 (LPGAT1). Mouse LPGAT1 is expressed in a number of tissues and most highly expressed in the liver. Hepatic LPGAT1 expression in diabetic db/db mice is higher than that in the control db/m mouse, which is consistent with increased hepatic MGAT activity in db/db mouse. To elucidate the role of LPGAT1 gene in lipid metabolism in db/db mice, we constructed an adenovirus of short hairpin RNA (shRNA) targeting LPGAT1 to selectively knockdown LPGAT1 gene expression in the liver. Hepatic MGAT activity and LPGAT1 expression in db/db mice infected with LPGAT1 shRNA adenovirus were significantly lower than those in mice infected with the control virus. Notably, treatment with LPGAT1 shRNA adenovirus caused a marked reduction in serum triacylglycerol and cholesterol levels and a significant increase in hepatic cholesterol level. These findings indicate that LPGAT1, a newly identified MGAT enzyme, plays a significant role in hepatic triacylglycerol synthesis and secretion in db/db mice.
Hiramine
Yasushi
Y
Dainippon-Sumitomo Pharma, Konohana-ku, Osaka 554-0022, Japan. yasushi-hiramine@ds-pharma.co.jp
Emoto
Hisayo
H
Takasuga
Shunsuke
S
Hiramatsu
Ryuji
R
D000818:Animals; D006224:Cricetinae; D051379:Mice; D000217:Acyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D016466:CHO Cells; D003412:Cricetulus; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D055029:Inverted Repeat Sequences; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D000217:Acyltransferases; D011994:Recombinant Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014280:Triglycerides; C000730756:Lpgat1 protein, mouse