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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Jacobs, René L. Gao, Xia Vance, Dennis E. Hermansson, Martin Ordoñez, Marta Gomez-muñoz, Antonio Van Der Veen, Jelske N. |
Description | Author Affiliation: Gao X ( Group on the Molecular and Cell Biology of Lipids and Department of Biochemistry, University of Alberta, Edmonton, Canada.); van der Veen JN ( Group on the Molecular and Cell Biology of Lipids and Department of Biochemistry, University of Alberta, Edmonton, Canada.); Hermansson M ( Group on the Molecular and Cell Biology of Lipids and Department of Biochemistry, University of Alberta, Edmonton, Canada.); Ordoñez M ( Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao, Spain.); Gomez-Muñoz A ( Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao, Spain.); Vance DE ( Group on the Molecular and Cell Biology of Lipids and Department of Biochemistry, University of Alberta, Edmonton, Canada.); Jacobs RL ( Group on the Molecular and Cell Biology of Lipids and Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada. Electronic address: rjacobs@ualberta.ca.) |
Abstract | Mice lacking phosphatidylethanolamine N-methyltransferase (PEMT, $Pemt^{−/−}$ mice) are resistant to high-fat diet (HFD)-induced obesity (DIO) but develop non-alcoholic steatohepatitis. PEMT expression is strongly induced during differentiation of 3T3-L1 adipocytes. Hence, we hypothesized that white adipose tissue (WAT) might be a key player in the protection against DIO in $Pemt^{−/−}$ mice. We fed $Pemt^{−/−}$ and $Pemt^{+/+}$ mice the HFD for 2 weeks, after which we examined adipocyte differentiation, adipogenesis and lipolysis in WAT. $Pemt^{−/−}$ mice gained less body weight, had reduced WAT mass and had smaller adipocytes than $Pemt^{+/+}$ mice. The protein levels of adipose differentiation markers FABP4, PPARγ and C/EBPβ were not altered by genotype, but acetyl-CoA carboxylase expression and activation was reduced in the $Pemt^{−/−}$ mice. The in vivo conversion of $[^{14}C]acetate$ to $[^{14}C]TG$ in WAT was also lower in $Pemt^{−/−}$ mice. The release of glycerol from WAT explants was comparable between $Pemt^{+/+}$ and $Pemt^{−/−}$ mice under basal condition and in the presence of isoproterenol, indicating unaffected lipolytic capacity. Furthermore, the amounts of leptin, cytokines and chemokines in WAT were not altered by genotype in mice fed the HFD for 2 weeks. However, after 10 weeks of HFD, WAT from $Pemt^{−/−}$ mice had dramatically lower leptin, inflammatory cytokines (IL-1 and TNF-α) and chemokines (MCP-1 and RANTES), and significantly higher anti-inflammatory cytokine IL-10 than $Pemt^{+/+}$ mice. Together, our data show that PEMT deficiency did not affect the capability for differentiation and lipolysis in WAT. Decreased lipogenesis in WAT may contribute to the resistance to DIO in $Pemt^{−/−}$ mice. |
ISSN | 00063002 |
Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
Issue Number | 2 |
Volume Number | 1851 |
Language | English |
Publisher | Elsevier |
Publisher Date | 2015-02-01 |
Publisher Place | Netherlands |
Access Restriction | Open |
Subject Keyword | Adipose Tissue, White Enzymology Diet, High-Fat Lipogenesis Obesity Prevention & Control Phosphatidylethanolamine N-Methyltransferase Deficiency Adipocytes, White Adipogenesis Physiopathology Adiposity Animals Biological Markers Metabolism Chemokines Cytokines Disease Models, Animal Down-Regulation Genotype Lipids Blood Lipolysis Mice, Inbred C57BL Mice, Knockout Genetics Phenotype Protective Factors Time Factors Weight Gain Research Support, Non-U.S. Gov't Biochemistry |
Content Type | Text |
Resource Type | Article |
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