Increased diacylglycerol acyltransferase activity is associated with triglyceride accumulation in tissues of diet-induced insulin-resistant hyperlipidemic hamsters.
Over-accumulation of triglyceride (TG) in insulin-sensitive tissues is associated with the development of insulin resistance. We investigated whether enhanced de novo lipogenesis via diacylglycerol acyltransferase (DGAT) may contribute to the over-accumulation of TG in various tissues (liver, adipose, muscle, and intestine) using 2 well-characterized hyperlipidemic, insulin-resistant hamster models. In general, a marked increase in TG accumulation was noted in most tissues. Interestingly, the increase in TG accumulation corresponded to an increase in microsomal DGAT activity which ranged from 114% to 575% in all of the examined tissues (n = 7 per group). To delineate the mechanism for the increase in DGAT activity, we measured the expression of DGAT-1 and DGAT-2 messenger RNA by relative reverse transcriptase polymerase chain reaction (RT-PCR). In general, DGAT gene expression changed with DGAT-1 changing the most in the liver and adipose tissue, whereas DGAT-2 showed responses mainly in muscle and intestine. The increases in messenger RNA expression were not remarkable (averaging 35%; n = 4 per group) indicating that posttranscriptional mechanism(s) may play a larger role in regulating DGAT activity. In summary, the data suggest that elevated DGAT activity/expression and the subsequent increase in de novo lipogenesis could in part induce the insulin-resistant state.
Casaschi
Adele
A
Division of Medical Technology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96822, USA.
Maiyoh
Geoffrey K
GK
Adeli
Khosrow
K
Theriault
Andre G
AG
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000097:blood; D006224:Cricetinae; D051048:Diacylglycerol O-Acyltransferase; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005632:Fructose / Q000008:administration & dosage; D015870:Gene Expression; D006949:Hyperlipidemias / Q000201:enzymology* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000201:enzymology; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009132:Muscles / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D012333:RNA, Messenger; D014280:Triglycerides; D005632:Fructose; D002784:Cholesterol; D000217:Acyltransferases; D051048:Diacylglycerol O-Acyltransferase