| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 273, Issue 45, 29577-29585, November 6, 1998
-Isoform
Deficiency Leads to Progressive Dyslipidemia with Sexually
Dimorphic Obesity and Steatosis
,,, and
From The Laboratoire de Pharmacologie et Toxicologie,
INRA, BP 3, 31931 Toulouse, Cedex 09 France and
§ Laboratoires Fournier SCA, Département
d'Athérosclérose, 50 Rue de Dijon,
21121 Daix, France
-isoform of the peroxisome
proliferator-activated receptor (PPAR) is a nuclear transcription
factor activated by structurally diverse chemicals referred to as
peroxisome proliferators. Activators can be endogenous molecules (fatty
acids/steroids) or xenobiotics (fibrate lipid-lowering drugs). Upon
pharmacological activation, PPAR modulates target genes encoding
lipid metabolism enzymes, lipid transporters, or apolipoproteins,
suggesting a role in lipid homeostasis. Transgenic mice deficient in
PPAR were shown to lack hepatic peroxisomal proliferation and have
an impaired expression and induction of several hepatic target genes.
Young adult males show hypercholesterolemia but normal triglycerides.
Using a long term experimental set up, we identified these mice as a
model of monogenic, spontaneous, late onset obesity with stable caloric intake and a marked sexual dimorphism. Serum triglycerides, elevated in
aged animals, are higher in females that develop a more pronounced obesity than males. The latter show a marked and original
centrilobular-restricted steatosis and a delayed occurrence of obesity.
Fat cells from their liver express substantial levels of PPAR
2
transcripts when compared with lean cells. These studies demonstrate,
in rodents, the involvement of PPAR nuclear receptor in lipid
homeostasis, with a sexually dimorphic control of circulating lipids,
fat storage, and obesity. Characterization of this pathological link
may help to delineate new molecular targets for therapeutic
intervention and could lead to new insights into the etiology and
heritability of mammalian obesity.
This article has been cited by other articles:
|
|
 |
|
  X. Ruan, F. Zheng, and Y. Guan PPARs and the kidney in metabolic syndrome Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1032 - F1047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Barbaric, M. J. Perry, T. N. Dear, A. Rodrigues Da Costa, D. Salopek, A. Marusic, T. Hough, S. Wells, A. J. Hunter, M. Cheeseman, et al. An ENU-induced mutation in the Ankrd11 gene results in an osteopenia-like phenotype in the mouse mutant Yoda Physiol Genomics, February 19, 2008; 32(3): 311 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Baumgardner, K. Shankar, L. Hennings, T. M. Badger, and M. J. J. Ronis A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G27 - G38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Cha, X. Zhang, Y. Zhang, J. Wu, D. Su, J. Y. Han, X. Fang, B. Yu, M. D. Breyer, and Y. Guan Peroxisome Proliferator Activated Receptor {alpha}/{gamma} Dual Agonist Tesaglitazar Attenuates Diabetic Nephropathy in db/db Mice Diabetes, August 1, 2007; 56(8): 2036 - 2045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Parent, D. Kolippakkam, G. Booth, and L. Beretta Mammalian Target of Rapamycin Activation Impairs Hepatocytic Differentiation and Targets Genes Moderating Lipid Homeostasis and Hepatocellular Growth Cancer Res., May 1, 2007; 67(9): 4337 - 4345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Y. Liu, R. S. Heymann, F. Moatamed, J. J. Schultz, D. Sobel, and G. A. Brent A Mutant Thyroid Hormone Receptor {alpha} Antagonizes Peroxisome Proliferator-Activated Receptor {alpha} Signaling in Vivo and Impairs Fatty Acid Oxidation Endocrinology, March 1, 2007; 148(3): 1206 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Ciana, A. Biserni, L. Tatangelo, C. Tiveron, A. F. Sciarroni, L. Ottobrini, and A. Maggi A Novel Peroxisome Proliferator-Activated Receptor Responsive Element-Luciferase Reporter Mouse Reveals Gender Specificity of Peroxisome Proliferator-Activated Receptor Activity in Liver Mol. Endocrinol., February 1, 2007; 21(2): 388 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ringseis, A. Muschick, and K. Eder Dietary Oxidized Fat Prevents Ethanol-Induced Triacylglycerol Accumulation and Increases Expression of PPAR{alpha} Target Genes in Rat Liver J. Nutr., January 1, 2007; 137(1): 77 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Rizki, L. Arnaboldi, B. Gabrielli, J. Yan, G. S. Lee, R. K. Ng, S. M. Turner, T. M. Badger, R. E. Pitas, and J. J. Maher Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1 J. Lipid Res., October 1, 2006; 47(10): 2280 - 2290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lambert, A.-L. Jarnoux, T. Pineau, O. Pape, M. Chetiveaux, C. Laboisse, M. Krempf, and P. Costet Fasting Induces Hyperlipidemia in Mice Overexpressing Proprotein Convertase Subtilisin Kexin Type 9: Lack of Modulation of Very-Low-Density Lipoprotein Hepatic Output by the Low-Density Lipoprotein Receptor Endocrinology, October 1, 2006; 147(10): 4985 - 4995. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. De Souza, X. Dai, A. G. Spencer, T. Reppen, A. Menzie, P. L. Roesch, Y. He, M. J. Caguyong, S. Bloomer, H. Herweijer, et al. Transcriptional and phenotypic comparisons of Ppara knockout and siRNA knockdown mice Nucleic Acids Res., September 11, 2006; 34(16): 4486 - 4494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yessoufou, A. Hichami, P. Besnard, K. Moutairou, and N. A. Khan Peroxisome Proliferator-Activated Receptor {alpha} Deficiency Increases the Risk of Maternal Abortion and Neonatal Mortality in Murine Pregnancy with or without Diabetes Mellitus: Modulation of T Cell Differentiation Endocrinology, September 1, 2006; 147(9): 4410 - 4418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Janoschek, L. Plum, L. Koch, H. Munzberg, S. Diano, M. Shanabrough, W. Muller, T. L. Horvath, and J. C. Bruning gp130 signaling in proopiomelanocortin neurons mediates the acute anorectic response to centrally applied ciliary neurotrophic factor PNAS, July 11, 2006; 103(28): 10707 - 10712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Vartanian, B. Lowell, I. G. Minko, T. G. Wood, J. D. Ceci, S. George, S. W. Ballinger, C. L. Corless, A. K. McCullough, and R. S. Lloyd The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase PNAS, February 7, 2006; 103(6): 1864 - 1869. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Murase, S. Haramizu, A. Shimotoyodome, A. Nagasawa, and I. Tokimitsu Green tea extract improves endurance capacity and increases muscle lipid oxidation in mice Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2005; 288(3): R708 - R715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Villareal and J. O. Holloszy Effect of DHEA on Abdominal Fat and Insulin Action in Elderly Women and Men: A Randomized Controlled Trial JAMA, November 10, 2004; 292(18): 2243 - 2248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Guan Peroxisome Proliferator-Activated Receptor Family and Its Relationship to Renal Complications of the Metabolic Syndrome J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2801 - 2815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. You and D. W. Crabb Recent Advances in Alcoholic Liver Disease II. Minireview: molecular mechanisms of alcoholic fatty liver Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G1 - G6. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Nanji, A. J. Dannenberg, K. Jokelainen, and N. M. Bass Alcoholic Liver Injury in the Rat Is Associated with Reduced Expression of Peroxisome Proliferator-{alpha} (PPAR{alpha})-Regulated Genes and Is Ameliorated by PPAR{alpha} Activation J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 417 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Genetically Modified Animals in Endocrinology Endocr. Rev., June 1, 2004; 25(3): 512 - 519. [Full Text] [PDF]
|
|
|
|
 |
|
 Q H Khan, D E Pontefract, S Iyengar, and S Ye Evidence of differing genotypic effects of PPAR{alpha} in women and men J. Med. Genet., June 1, 2004; 41(6): e79 - e79. [Full Text] [PDF]
|
|
|
|
|
|
B. P. Atshaves, H. R. Payne, A. L. McIntosh, S. E. Tichy, D. Russell, A. B. Kier, and F. Schroeder Sexually dimorphic metabolism of branched-chain lipids in C57BL/6J mice J. Lipid Res., May 1, 2004; 45(5): 812 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Gavrilova, M. Haluzik, K. Matsusue, J. J. Cutson, L. Johnson, K. R. Dietz, C. J. Nicol, C. Vinson, F. J. Gonzalez, and M. L. Reitman Liver Peroxisome Proliferator-activated Receptor {gamma} Contributes to Hepatic Steatosis, Triglyceride Clearance, and Regulation of Body Fat Mass J. Biol. Chem., September 5, 2003; 278(36): 34268 - 34276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Larsen, P. B. Jensen, R. V. Sorensen, L. K. Larsen, N. Vrang, E. M. Wulff, and K. Wassermann Differential Influences of Peroxisome Proliferator-Activated Receptors{gamma} and -{alpha} on Food Intake and Energy Homeostasis Diabetes, September 1, 2003; 52(9): 2249 - 2259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ide, H. Shimano, T. Yoshikawa, N. Yahagi, M. Amemiya-Kudo, T. Matsuzaka, M. Nakakuki, S. Yatoh, Y. Iizuka, S. Tomita, et al. Cross-Talk between Peroxisome Proliferator-Activated Receptor (PPAR) {alpha} and Liver X Receptor (LXR) in Nutritional Regulation of Fatty Acid Metabolism. II. LXRs Suppress Lipid Degradation Gene Promoters through Inhibition of PPAR Signaling Mol. Endocrinol., July 1, 2003; 17(7): 1255 - 1267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Francis, J.-S. Annicotte, and J. Auwerx PPAR-{alpha} effects on the heart and other vascular tissues Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H1 - H9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-J. Y. Wan, G. Han, Y. Cai, T. Dai, T. Konishi, and A.-S. Leng Hepatocyte Retinoid X Receptor-{alpha}-Deficient Mice Have Reduced Food Intake, Increased Body Weight, and Improved Glucose Tolerance Endocrinology, February 1, 2003; 144(2): 605 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakatani, H.-J. Kim, Y. Kaburagi, K. Yasuda, and O. Ezaki A low fish oil inhibits SREBP-1 proteolytic cascade, while a high-fish-oil feeding decreases SREBP-1 mRNA in mice liver: relationship to anti-obesity J. Lipid Res., February 1, 2003; 44(2): 369 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Huang, O. Starodub, A. McIntosh, A. B. Kier, and F. Schroeder Liver Fatty Acid-binding Protein Targets Fatty Acids to the Nucleus. REAL TIME CONFOCAL AND MULTIPHOTON FLUORESCENCE IMAGING IN LIVING CELLS J. Biol. Chem., August 2, 2002; 277(32): 29139 - 29151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Rajas, A. Gautier, I. Bady, S. Montano, and G. Mithieux Polyunsaturated Fatty Acyl Coenzyme A Suppress the Glucose-6-phosphatase Promoter Activity by Modulating the DNA Binding of Hepatocyte Nuclear Factor 4alpha J. Biol. Chem., May 3, 2002; 277(18): 15736 - 15744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Clark The role of PPARs in inflammation and immunity J. Leukoc. Biol., March 1, 2002; 71(3): 388 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Yamakawa-Kobayashi, H Ishiguro, T Arinami, R Miyazaki, and H Hamaguchi A Val227Ala polymorphism in the peroxisome proliferator activated receptor {alpha} (PPAR{alpha}) gene is associated with variations in serum lipid levels J. Med. Genet., March 1, 2002; 39(3): 189 - 191. [Full Text]
|
|
|
|
|
|
M. Guerre-Millo, C. Rouault, P. Poulain, J. Andre, V. Poitout, J. M. Peters, F. J. Gonzalez, J.-C. Fruchart, G. Reach, and B. Staels PPAR-{alpha}-Null Mice Are Protected From High-Fat Diet-Induced Insulin Resistance Diabetes, December 1, 2001; 50(12): 2809 - 2814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-M. Chao, C.-Y. Chao, F.-J. Lin, and C.-j. Huang Oxidized Frying Oil Up-Regulates Hepatic Acyl-CoA Oxidase and Cytochrome P450 4 A1 Genes in Rats and Activates PPAR{alpha} J. Nutr., December 1, 2001; 131(12): 3166 - 3174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Linden, M. Alsterholm, H. Wennbo, and J. Oscarsson PPAR{alpha} deficiency increases secretion and serum levels of apolipoprotein B-containing lipoproteins J. Lipid Res., November 1, 2001; 42(11): 1831 - 1840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Akiyama, C. J. Nicol, C. Fievet, B. Staels, J. M. Ward, J. Auwerx, S. S. T. Lee, F. J. Gonzalez, and J. M. Peters Peroxisome Proliferator-activated Receptor-alpha Regulates Lipid Homeostasis, but Is Not Associated with Obesity. STUDIES WITH CONGENIC MOUSE LINES J. Biol. Chem., October 12, 2001; 276(42): 39088 - 39093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Wallenius, K. Wallenius, M. Hisaoka, J. Sandstedt, C. Ohlsson, M. Kopf, and J.-O. Jansson Retarded Liver Growth in Interleukin-6-Deficient and Tumor Necrosis Factor Receptor-1-Deficient Mice Endocrinology, July 1, 2001; 142(7): 2953 - 2960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Kissebah, G. E. Sonnenberg, J. Myklebust, M. Goldstein, K. Broman, R. G. James, J. A. Marks, G. R. Krakower, H. J. Jacob, J. Weber, et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome PNAS, December 19, 2000; 97(26): 14478 - 14483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lazennec, L. Canaple, D. Saugy, and W. Wahli Activation of Peroxisome Proliferator-Activated Receptors (PPARs) by Their Ligands and Protein Kinase A Activators Mol. Endocrinol., December 1, 2000; 14(12): 1962 - 1975. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. G. DeLuca, T. W. Doebber, L. J. Kelly, R. K. Kemp, S. Molon-Noblot, S. P. Sahoo, J. Ventre, M. S. Wu, J. M. Peters, F. J. Gonzalez, et al. Evidence for Peroxisome Proliferator-Activated Receptor (PPAR)alpha -Independent Peroxisome Proliferation: Effects of PPARgamma /delta -Specific Agonists in PPARalpha -Null Mice Mol. Pharmacol., September 1, 2000; 58(3): 470 - 476. [Abstract] [Full Text]
|
|
|
|
|
|
M. Marrapodi and J. Y. L. Chiang Peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) and agonist inhibit cholesterol 7{alpha}-hydroxylase gene (CYP7A1) transcription J. Lipid Res., March 1, 2000; 41(3): 514 - 520. [Abstract] [Full Text]
|
|
|
|
|
|
M. Marrapodi and J. Y. L. Chiang Peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) and agonist inhibit cholesterol 7{alpha}-hydroxylase gene (CYP7A1) transcription J. Lipid Res., March 1, 2000; 41(4): 514 - 520. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. B. Vega, J. M. Huss, and D. P. Kelly The Coactivator PGC-1 Cooperates with Peroxisome Proliferator-Activated Receptor alpha in Transcriptional Control of Nuclear Genes Encoding Mitochondrial Fatty Acid Oxidation Enzymes Mol. Cell. Biol., March 1, 2000; 20(5): 1868 - 1876. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Inui Transgenic Approach to the Study of Body Weight Regulation Pharmacol. Rev., March 1, 2000; 52(1): 35 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D Clarke, P. Thuillier, R. A Baillie, and X. Sha Peroxisome proliferator-activated receptors: a family of lipid-activated transcription factors Am. J. Clinical Nutrition, October 1, 1999; 70(4): 566 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Desvergne and W. Wahli Peroxisome Proliferator-Activated Receptors: Nuclear Control of Metabolism Endocr. Rev., October 1, 1999; 20(5): 649 - 688. [Abstract] [Full Text]
|
|
|
|
|
|
D. Chen and A. Garg Monogenic disorders of obesity and body fat distribution J. Lipid Res., October 1, 1999; 40(10): 1735 - 1746. [Abstract] [Full Text]
|
|
|
|
|
|
T. B. Barclay, J. M. Peters, M. B. Sewer, L. Ferrari, F. J. Gonzalez, and E. T. Morgan Modulation of Cytochrome P-450 Gene Expression in Endotoxemic Mice Is Tissue Specific and Peroxisome Proliferator-Activated Receptor-alpha Dependent J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 1250 - 1257. [Abstract] [Full Text]
|
|
|
|
|
|
T. Hashimoto, T. Fujita, N. Usuda, W. Cook, C. Qi, J. M. Peters, F. J. Gonzalez, A. V. Yeldandi, M. S. Rao, and J. K. Reddy Peroxisomal and Mitochondrial Fatty Acid beta -Oxidation in Mice Nullizygous for Both Peroxisome Proliferator-activated Receptor alpha and Peroxisomal Fatty Acyl-CoA Oxidase. GENOTYPE CORRELATION WITH FATTY LIVER PHENOTYPE J. Biol. Chem., July 2, 1999; 274(27): 19228 - 19236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Edvardsson, M. Bergström, M. Alexandersson, K. Bamberg, B. Ljung, and B. Dahllöf Rosiglitazone (BRL49653), a PPAR{gamma}-selective agonist, causes peroxisome proliferator-like liver effects in obese mice J. Lipid Res., July 1, 1999; 40(7): 1177 - 1184. [Abstract] [Full Text]
|
|
|
|
|
|
T. C. Leone, C. J. Weinheimer, and D. P. Kelly A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha ) in the cellular fasting response: The PPARalpha -null mouse as a model of fatty acid oxidation disorders PNAS, June 22, 1999; 96(13): 7473 - 7478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Kliewer, J. M. Lehmann, and T. M. Willson Orphan Nuclear Receptors: Shifting Endocrinology into Reverse Science, April 30, 1999; 284(5415): 757 - 760. [Abstract] [Full Text]
|
|
|
|
|
|
Y.-J. Y. Wan, Y. Cai, W. Lungo, P. Fu, J. Locker, S. French, and H. M. Sucov Peroxisome Proliferator-activated Receptor alpha -mediated Pathways Are Altered in Hepatocyte-specific Retinoid X Receptor alpha -deficient Mice J. Biol. Chem., September 1, 2000; 275(36): 28285 - 28290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Barbera, A. Schluter, N. Pedraza, R. Iglesias, F. Villarroya, and M. Giralt Peroxisome Proliferator-activated Receptor alpha Activates Transcription of the Brown Fat Uncoupling Protein-1 Gene. A LINK BETWEEN REGULATION OF THE THERMOGENIC AND LIPID OXIDATION PATHWAYS IN THE BROWN FAT CELL J. Biol. Chem., January 5, 2001; 276(2): 1486 - 1493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Barger, A. C. Browning, A. N. Garner, and D. P. Kelly p38 Mitogen-activated Protein Kinase Activates Peroxisome Proliferator-activated Receptor alpha . A POTENTIAL ROLE IN THE CARDIAC METABOLIC STRESS RESPONSE J. Biol. Chem., November 21, 2001; 276(48): 44495 - 44501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Jamshidi, H. E. Montgomery, H.-W. Hense, S. G. Myerson, I. P. Torra, B. Staels, M. J. World, A. Doering, J. Erdmann, C. Hengstenberg, et al. Peroxisome Proliferator-Activated Receptor {alpha} Gene Regulates Left Ventricular Growth in Response to Exercise and Hypertension Circulation, February 26, 2002; 105(8): 950 - 955. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
