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PMID: 11956242 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1.

The Journal of clinical investigation ·Vol. 109 ·No. 8 ·2002-04-00 ·Pages 1049-55

Chen HC, Smith SJ, Ladha Z, Jensen DR, Ferreira LD, Pulawa LK, McGuire JG, Pitas RE, Eckel RH, Farese RV

Abstract

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.

MeSH Terms
Acyltransferases/deficiency,genetics,metabolism Adipocytes/pathology Animals Cell Size Diacylglycerol O-Acyltransferase Energy Metabolism Humans Insulin/pharmacology Insulin Resistance Leptin/pharmacology Lipid Metabolism Mice Mice, Inbred C57BL Mice, Knockout Mice, Mutant Strains Mice, Obese Obesity/etiology,metabolism Tissue Distribution Triglycerides/metabolism Weight Loss/drug effects
Chemicals
Insulin Leptin Triglycerides Acyltransferases DGAT1 protein, human DGAT2 protein, human Dgat1 protein, mouse Diacylglycerol O-Acyltransferase
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Chen Hubert C
Gladstone Institute of Cardiovascular Disease, PO Box 419100, San Francisco, California 94141-9100, USA.
Smith Steven J
Ladha Zuleika
Jensen Dalan R
Ferreira Luis D
Pulawa Leslie K
McGuire James G
Pitas Robert E
Eckel Robert H
Farese Robert V
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI14672
Published
2002-04-00
Pages
1049-55
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC150948
Subset
IM
Grants
NIDDK NIH HHS · DK-56804 · United States
NIDDK NIH HHS · DK-26356 · United States
NIDDK NIH HHS · R01 DK056804 · United States
NIDDK NIH HHS · R01 DK026356 · United States
NIDDK NIH HHS · R01 DK056084 · United States
External Links
PubMed source DOI: 10.1172/JCI14672 PMC Full Text View journal details
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