Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1.
Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final step in mammalian triglyceride synthesis. DGAT1-deficient mice are resistant to diet-induced obesity through a mechanism involving increased energy expenditure. Here we show that these mice have decreased levels of tissue triglycerides, as well as increased sensitivity to insulin and to leptin. Importantly, DGAT1 deficiency protects against insulin resistance and obesity in agouti yellow mice, a model of severe leptin resistance. In contrast, DGAT1 deficiency did not affect energy and glucose metabolism in leptin-deficient (ob/ob) mice, possibly due in part to a compensatory upregulation of DGAT2 expression in the absence of leptin. Our results suggest that inhibition of DGAT1 may be useful in treating insulin resistance and leptin resistance in human obesity.
Chen
Hubert C
HC
Gladstone Institute of Cardiovascular Disease, PO Box 419100, San Francisco, California 94141-9100, USA.
Smith
Steven J
SJ
Ladha
Zuleika
Z
Jensen
Dalan R
DR
Ferreira
Luis D
LD
Pulawa
Leslie K
LK
McGuire
James G
JG
Pitas
Robert E
RE
Eckel
Robert H
RH
Farese
Robert V
RV
D000217:Acyltransferases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000473:pathology; D000818:Animals; D048429:Cell Size; D051048:Diacylglycerol O-Acyltransferase; D004734:Energy Metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D020738:Leptin / Q000494:pharmacology*; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D014018:Tissue Distribution; D014280:Triglycerides / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D000217:Acyltransferases; C494881:DGAT1 protein, human; C494885:DGAT2 protein, human; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase