Role of adipocyte-derived factors in enhancing insulin signaling in skeletal muscle and white adipose tissue of mice lacking Acyl CoA:diacylglycerol acyltransferase 1.
Mice that lack acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in mammalian triglyceride synthesis, have decreased adiposity and increased insulin sensitivity. Here we show that insulin-stimulated glucose transport is increased in the skeletal muscle and white adipose tissue (WAT) of chow-fed DGAT1-deficient mice. This increase in glucose transport correlated with enhanced insulin-stimulated activities of phosphatidylinositol 3-kinase, protein kinase B (or Akt), and protein kinase Clambda (PKC-lambda), three key molecules in the insulin-signaling pathway, and was associated with decreased levels of serine-phosphorylated insulin receptor substrate 1 (IRS-1), a molecule implicated in insulin resistance. Similar findings in insulin signaling were also observed in DGAT1-deficient mice fed a high-fat diet. Interestingly, the increased PKC-lambda activity and decreased serine phosphorylation of IRS-1 were observed in chow-fed wild-type mice transplanted with DGAT1-deficient WAT, consistent with our previous finding that transplantation of DGAT1-deficient WAT enhances glucose disposal in wild-type recipient mice. Our findings demonstrate that DGAT1 deficiency enhances insulin signaling in the skeletal muscle and WAT, in part through altered expression of adipocyte-derived factors that modulate insulin signaling in peripheral tissues.
Chen
Hubert C
HC
James A. Haley Veterans Hospital, ACOS-151, 13000 Bruce B. Downs Blvd., Tampa, FL 33612, USA.
Rao
Meghana
M
Sajan
Mini P
MP
Standaert
Mary
M
Kanoh
Yoshinori
Y
Miura
Atsushi
A
Farese
Robert V
RV
Farese
Robert V
RV
D000217:Acyltransferases / Q000172:deficiency* / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism* / Q000637:transplantation; D000818:Animals; D051048:Diacylglycerol O-Acyltransferase; D004041:Dietary Fats / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction
D000217:Acyltransferases; D051048:Diacylglycerol O-Acyltransferase; D004041:Dietary Fats; D005947:Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine; C526295:Irs1 protein, mouse; C494882:Dgat1 protein, mouse