This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sartippour, M. R. Articles by Renier, G. Search for Related Content PubMed PubMed Citation Articles by Sartippour, M. R. Articles by Renier, G. Related Collections Pathophysiology Risk Factors Cell signalling/signal transduction Physiological and pathological control of gene expression Lipid and lipoprotein metabolism

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:104.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Differential Regulation of Macrophage Peroxisome Proliferator–Activated Receptor Expression by Glucose

Role of Peroxisome Proliferator–Activated Receptors in Lipoprotein Lipase Gene Expression

Maryam Radimeh Sartippour; Geneviève Renier

From Centre Hospitalier de l’Université de Montréal Research Center, Notre-Dame Hospital, Department of Nutrition, University of Montreal, Montreal, Quebec, Canada.

Abstract—Peroxisome proliferator–activated receptors (PPARs) are implicated in several metabolic disorders with altered glucose and lipid metabolism, including atherosclerosis and diabetes. In the present study, we evaluated the in vitro and ex vivo effects of high glucose concentrations on macrophage PPAR mRNA expression. Exposition of monocyte-derived macrophages isolated from healthy donors to a high glucose environment led to an increase in PPAR and PPARß mRNA expression. In contrast, this treatment significantly decreased human macrophage PPAR mRNA expression. Overexpression of PPAR and PPARß mRNA and inhibition of PPAR mRNA expression were also observed in monocyte-derived macrophages isolated from patients with type 2 diabetes. Because high glucose and PPAR agonists increase lipoprotein lipase (LPL) gene expression, the role of PPAR in the glucose-mediated upregulation of macrophage LPL gene expression was next evaluated. Incubation of murine J774 macrophages with high glucose concentrations increased the expression of PPAR at the mRNA and protein levels and enhanced nuclear protein binding to the peroxisome proliferator responsive element of the LPL promoter. Incubation of nuclear extracts in the presence of anti-PPAR and anti-PPARß antibodies decreased glucose-stimulated nuclear protein binding to the peroxisome proliferator responsive element. These results demonstrate that glucose is an important regulator of macrophage PPAR expression and suggest a role of PPAR and PPARß in the upregulation of macrophage LPL by glucose. Dysregulation of macrophage PPAR expression in type 2 diabetes may contribute, by altering arterial lipid metabolism and inflammatory response, to the accelerated atherosclerosis associated with diabetes.

Key Words: peroxisome proliferator–activated receptors • macrophage • glucose • lipoprotein lipase

This article has been cited by other articles:

				R. Nielsen, L. Grontved, H. G. Stunnenberg, and S. Mandrup Peroxisome Proliferator-Activated Receptor Subtype- and Cell-Type-Specific Activation of Genomic Target Genes upon Adenoviral Transgene Delivery Mol. Cell. Biol., August 1, 2006; 26(15): 5698 - 5714. [Abstract] [Full Text] [PDF]

				H. W. Cohen, S. M. Hailpern, and M. H. Alderman Glucose-Cholesterol Interaction Magnifies Coronary Heart Disease Risk for Hypertensive Patients Hypertension, May 1, 2004; 43(5): 983 - 987. [Abstract] [Full Text] [PDF]

				I. Pineda Torra, Y. Jamshidi, D. M. Flavell, J.-C. Fruchart, and B. Staels Characterization of the Human PPAR{alpha} Promoter: Identification of a Functional Nuclear Receptor Response Element Mol. Endocrinol., May 1, 2002; 16(5): 1013 - 1028. [Abstract] [Full Text] [PDF]

				M.-C. Beauchamp and G. Renier Homocysteine Induces Protein Kinase C Activation and Stimulates c-Fos and Lipoprotein Lipase Expression in Macrophages Diabetes, April 1, 2002; 51(4): 1180 - 1187. [Abstract] [Full Text] [PDF]

				T. R. Hughes, T. S. Tengku-Muhammad, S. A. Irvine, and D. P. Ramji A Novel Role of Sp1 and Sp3 in the Interferon-gamma -mediated Suppression of Macrophage Lipoprotein Lipase Gene Transcription J. Biol. Chem., March 22, 2002; 277(13): 11097 - 11106. [Abstract] [Full Text] [PDF]

				Y. Zhang, J. J. Repa, K. Gauthier, and D. J. Mangelsdorf Regulation of Lipoprotein Lipase by the Oxysterol Receptors, LXRalpha and LXRbeta J. Biol. Chem., November 9, 2001; 276(46): 43018 - 43024. [Abstract] [Full Text] [PDF]

				A.-Y. Tu and J. J. Albers Glucose Regulates the Transcription of Human Genes Relevant to HDL Metabolism: Responsive Elements for Peroxisome Proliferator-Activated Receptor Are Involved in the Regulation of Phospholipid Transfer Protein Diabetes, August 1, 2001; 50(8): 1851 - 1856. [Abstract] [Full Text] [PDF]

				E. Chevillotte, J. Rieusset, M. Roques, M. Desage, and H. Vidal The Regulation of Uncoupling Protein-2 Gene Expression by omega -6 Polyunsaturated Fatty Acids in Human Skeletal Muscle Cells Involves Multiple Pathways, Including the Nuclear Receptor Peroxisome Proliferator-activated Receptor beta J. Biol. Chem., March 30, 2001; 276(14): 10853 - 10860. [Abstract] [Full Text] [PDF]

				F. Zheng, A. Fornoni, S. J. Elliot, Y. Guan, M. D. Breyer, L. J. Striker, and G. E. Striker Upregulation of type I collagen by TGF-beta in mesangial cells is blocked by PPARgamma activation Am J Physiol Renal Physiol, April 1, 2002; 282(4): F639 - F648. [Abstract] [Full Text] [PDF]