DGAT1 deficiency decreases PPAR expression and does not lead to lipotoxicity in cardiac and skeletal muscle

J Lipid Res. 2011 Apr;52(4):732-44. doi: 10.1194/jlr.M011395. Epub 2011 Jan 3.


Diacylglycerol (DAG) acyl transferase 1 (Dgat1) knockout ((-/-)) mice are resistant to high-fat-induced obesity and insulin resistance, but the reasons are unclear. Dgat1(-/-) mice had reduced mRNA levels of all three Ppar genes and genes involved in fatty acid oxidation in the myocardium of Dgat1(-/-) mice. Although DGAT1 converts DAG to triglyceride (TG), tissue levels of DAG were not increased in Dgat1(-/-) mice. Hearts of chow-diet Dgat1(-/-) mice were larger than those of wild-type (WT) mice, but cardiac function was normal. Skeletal muscles from Dgat1(-/-) mice were also larger. Muscle hypertrophy factors phospho-AKT and phospho-mTOR were increased in Dgat1(-/-) cardiac and skeletal muscle. In contrast to muscle, liver from Dgat1(-/-) mice had no reduction in mRNA levels of genes mediating fatty acid oxidation. Glucose uptake was increased in cardiac and skeletal muscle in Dgat1(-/-) mice. Treatment with an inhibitor specific for DGAT1 led to similarly striking reductions in mRNA levels of genes mediating fatty acid oxidation in cardiac and skeletal muscle. These changes were reproduced in cultured myocytes with the DGAT1 inhibitor, which also blocked the increase in mRNA levels of Ppar genes and their targets induced by palmitic acid. Thus, loss of DGAT1 activity in muscles decreases mRNA levels of genes involved in lipid uptake and oxidation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Animals
  • Blotting, Western
  • Cell Line
  • Ceramides / metabolism
  • Diacylglycerol O-Acyltransferase / deficiency
  • Diacylglycerol O-Acyltransferase / genetics
  • Diacylglycerol O-Acyltransferase / metabolism*
  • Diglycerides / metabolism
  • Echocardiography
  • Enzyme Inhibitors / pharmacology
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Glucose / metabolism
  • Lipoproteins, VLDL / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / metabolism*
  • Myoblasts / drug effects
  • Myoblasts / metabolism
  • Myocardium / metabolism*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Organ Size / genetics
  • Palmitic Acid / pharmacology
  • Peroxisome Proliferator-Activated Receptors / genetics*
  • Polymerase Chain Reaction


  • Ceramides
  • Diglycerides
  • Enzyme Inhibitors
  • Lipoproteins, VLDL
  • Peroxisome Proliferator-Activated Receptors
  • Palmitic Acid
  • Dgat1 protein, mouse
  • Diacylglycerol O-Acyltransferase
  • Glucose