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  • Title: Increased diacylglycerol acyltransferase activity is associated with triglyceride accumulation in tissues of diet-induced insulin-resistant hyperlipidemic hamsters.
    Author: Casaschi A, Maiyoh GK, Adeli K, Theriault AG.
    Journal: Metabolism; 2005 Mar; 54(3):403-9. PubMed ID: 15736121.
    Abstract:
    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.
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