Mechanisms of the depot specificity of peroxisome proliferator-activated receptor γ action on adipose tissue metabolism.
Open accessAbstract
In this study, we aimed to establish the mechanisms whereby peroxisome proliferator-activated receptor gamma (PPARgamma) agonism brings about redistribution of fat toward subcutaneous depots and away from visceral fat. In rats treated with the full PPARgamma agonist COOH (30 mg x kg(-1) x day(-1)) for 3 weeks, subcutaneous fat mass was doubled and that of visceral fat was reduced by 30% relative to untreated rats. Uptake of triglyceride-derived nonesterified fatty acids was greatly increased in subcutaneous fat (14-fold) and less so in visceral fat (4-fold), with a concomitant increase, restricted to subcutaneous fat only, in mRNA levels of the uptake-, retention-, and esterification-promoting enzymes lipoprotein lipase, aP2, and diacylglycerol acyltransferase 1. Basal lipolysis and fatty acid recycling were stimulated by COOH in both subcutaneous fat and visceral fat, with no frank quantitative depot specificity. The agonist increased mRNA levels of enzymes of fatty acid oxidation and thermogenesis much more strongly in visceral fat than in subcutaneous fat, concomitantly with a stronger elevation in O2 consumption in the former than in the latter. Mitochondrial biogenesis was stimulated equally in both depots. These findings demonstrate that PPARgamma agonism redistributes fat by stimulating the lipid uptake and esterification potential in subcutaneous fat, which more than compensates for increased O2 consumption; conversely, lipid uptake is minimally altered and energy expenditure is greatly increased in visceral fat, with consequent reduction in fat accumulation.
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Administration of thiazolidinediones induces changes in mitochondrial content and remodeling in white adipocytes concomitantly with an improvement in insulin sensitivity.
“Administration of thiazolidinediones induces changes in mitochondrial content and remodeling in white adipocytes concomitantly with an improvement in insulin sensitivity (170, 173, 177, 190, 194 -198).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [198]
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Cites
Metabolism of Isolated Fat Cells
Rodbell, M. (1964) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)51687-2 · Cited by 4,647 · see citing works
Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome
Wajchenberg, B. L. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.6.0415 · Cited by 2,961 · see citing works
The mechanisms of action of PPARs
Berger, J., & Moller, D. E. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.104018 · Cited by 2,659 · see citing works
Self-citationMetabolic control through the PGC-1 family of transcription coactivators
Lin, J., Handschin, C., & Spiegelman, B. M. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.004 · Cited by 2,130 · cited 1× · see citing works
“A further indication of this is the COOH-induced increase in the expression of PGC-1 , a molecular switch that turns on several key components of the adaptive thermogenic program in brown fat (41).”
BackgroundRelation of Body Fat Distribution to Metabolic Complications of Obesity*
KISSEBAH, A. H., VYDELINGUM, N., MURRAY, R., EVANS, D. J., KALKHOFF, R. K., & ADAMS, P. W. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-54-2-254 · Cited by 1,909 · see citing works
PPAR-gamma: adipogenic regulator and thiazolidinedione receptor.
Spiegelman, B. M. (1998) · Diabetes · doi:10.2337/diabetes.47.4.507 · Cited by 1,730 · see citing works
Yu, C., Chen, Y., Cline, G. W., Zhang, D., Zong, H., Wang, Y., Bergeron, R., Kim, J. K., Cushman, S. W., Cooney, G. J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200958200 · Cited by 1,561 · see citing works
Krotkiewski, M., Björntorp, P. A., Sjöström, L., & Smith, U. (1983) · Journal of Clinical Investigation · doi:10.1172/jci111040 · Cited by 1,448 · see citing works
Minireview: Adiposity, Inflammation, and Atherogenesis
Lyon, C. J., Law, R. E., & Hsueh, W. A. (2003) · Endocrinology · doi:10.1210/en.2003-0285 · Cited by 761 · see citing works
Miyazaki, Y., Mahankali, A., Matsuda, M., Mahankali, S., Hardies, J., Cusi, K., Mandarino, L. J., & DeFronzo, R. A. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.6.8567 · Cited by 726 · see citing works
Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone.
Wilson-Fritch, L., Nicoloro, S., Chouinard, M., Lazar, M. A., Chui, P. C., Leszyk, J., Straubhaar, J., Czech, M. P., & Corvera, S. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21752 · Cited by 616 · see citing works
Regional obesity and risk of cardiovascular disease; the Framingham study
Kannel, W. B., Cupples, L. A., Ramaswami, R., Stokes, J., Kreger, B. E., & HIGGINS, M. W. (1991) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(91)90265-b · Cited by 533 · see citing works
Adams, M., Montague, C. T., Prins, J. B., Holder, J. C., Smith, S. A., Sanders, L., Digby, J., Sewter, C. P., Lazar, M. A., Chatterjee, K., et al. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119870 · Cited by 516 · see citing works
Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation
Holness, M. J., & Sugden, M. C. (2003) · Biochemical Society Transactions · doi:10.1042/bst0311143 · Cited by 479 · see citing works
Acquirement of brown fat cell features by human white adipocytes
Tiraby, C., Tavernier, G., Lefort, C., Larrouy, D., Bouillaud, F., Ricquier, D., & Langin, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305235200 · Cited by 474 · cited 1× · see citing works
“Overexpression of PGC-1 in white adipocytes increases UCP-1 expression, proteins of the respiratory chain, and fatty acid oxidation exactly as occurs in brown adipose cells (42).”
BackgroundPioglitazone Induces Mitochondrial Biogenesis in Human Subcutaneous Adipose Tissue In Vivo
Bogacka, I., Xie, H., Bray, G. A., & Smith, S. R. (2005) · Diabetes · doi:10.2337/diabetes.54.5.1392 · Cited by 467 · see citing works
SRC-1 and TIF2 Control Energy Balance between White and Brown Adipose Tissues
Picard, F., Géhin, M., Annicotte, J., Rocchi, S., Champy, M., O’Malley, B. W., Chambon, P., & Auwerx, J. H. (2002) · Cell · doi:10.1016/s0092-8674(02)01169-8 · Cited by 444 · see citing works
Nuclear receptor corepressor RIP140 regulates fat accumulation
Leonardsson, G., Steel, J. H., Christian, M., Pocock, V., Milligan, S., Bell, J., So, P.-W., Medina-Gomez, G., Vidal-Puig, A., White, R., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401013101 · Cited by 366 · see citing works
Depot-Specific Differences in Adipose Tissue Gene Expression in Lean and Obese Subjects
Lefebvre, A., Laville, M., Véga, N., Riou, J. P., Gaal, L. V., Auwerx, J. H., & Vidal, H. (1998) · Diabetes · doi:10.2337/diab.47.1.98 · Cited by 365 · see citing works
de Souza, C. J., Eckhardt, M., Gagen, K., Dong, M., Chen, W., Laurent, D., & Burkey, B. F. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1863 · Cited by 351 · see citing works
Way, J. M., Harrington, W. W., Brown, K. K., Gottschalk, W. K., Sundseth, S. S., Mansfield, T. A., Ramachandran, R. K., Willson, T. M., & Kliewer, S. A. (2001) · Endocrinology · doi:10.1210/endo.142.3.8037 · Cited by 338 · see citing works
Depot-related gene expression in human subcutaneous and omental adipocytes.
Montague, C. T., Prins, J. B., Sanders, L., Zhang, J., Sewter, C. P., Digby, J., Byrne, C. D., & O’Rahilly, S. (1998) · Diabetes · doi:10.2337/diabetes.47.9.1384 · Cited by 331 · see citing works
Fatty acid regulation of very low density lipoprotein production
Lewis, G. F. (1997) · Current Opinion in Lipidology · doi:10.1097/00041433-199706000-00004 · Cited by 296 · see citing works
Mechanisms of the free fatty acid-induced increase in hepatic glucose production
Lam, T. K. T., Carpentier, A. C., Lewis, G. F., van de Werve, G., Fantus, I. G., & Giacca, A. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00033.2003 · Cited by 283 · see citing works
Effect of troglitazone on body fat distribution in type 2 diabetic patients.
Mori, Y., Murakawa, Y., Okada, K., Horikoshi, H., Yokoyama, J., Tajima, N., & Ikeda, Y. (1999) · Diabetes Care · doi:10.2337/diacare.22.6.908 · Cited by 281 · see citing works
Neurobiological basis of depression: an update
Kalia, M. (2005) · Metabolism · doi:10.1016/j.metabol.2005.01.009 · Cited by 202 · see citing works
Thiazolidinediones Block Fatty Acid Release by Inducing Glyceroneogenesis in Fat Cells
Tordjman, J., Chauvet, G., Quette, J., BEALE, E. G., Forest, C. D., & Antoine, B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m206999200 · Cited by 177 · see citing works
Effect of pioglitazone on body composition and energy expenditure: a randomized controlled trial
Smith, S. R., de Jonge, L., Volaufova, J., Li, Y., Xie, H., & Bray, G. A. (2005) · Metabolism · doi:10.1016/j.metabol.2004.07.008 · Cited by 176 · see citing works
Oakes, N. D., Thalén, P., Jacinto, S. M., & Ljung, B. (2001) · Diabetes · doi:10.2337/diabetes.50.5.1158 · Cited by 168 · see citing works
LIPOLYSIS:Contribution from Regional Fat
Jensen, M. D. (1997) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.17.1.127 · Cited by 157 · cited 1× · see citing works
“Visceral fat releases more nonesterified fatty acids (NEFAs) into circulation than subcutaneous fat (4,5), which is liable to expose the liver to high amounts of NEFAs and to increase hepatic glucose production and VLDL secretion (6,7).”
BackgroundKanety, H., Hemi, R., Papa, M. Z., & Karasik, A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.17.9895 · Cited by 153 · see citing works
Laplante, M., Sell, H., MacNaul, K. L., Richard, D., Berger, J. P., & Deshaies, Y. (2003) · Diabetes · doi:10.2337/diabetes.52.2.291 · Cited by 153 · see citing works
Self-citationFestuccia, W. T., Laplante, M., Berthiaume, M., Gélinas, Y., & Deshaies, Y. (2006) · Diabetologia · doi:10.1007/s00125-006-0336-y · Cited by 140 · see citing works
Self-citationYe, J.-M., Dzamko, N. L., Cleasby, M. E., Hegarty, B. D., Furler, S. M., Cooney, G. J., & Kraegen, E. W. (2004) · Diabetologia · doi:10.1007/s00125-004-1436-1 · Cited by 137 · see citing works
Chen, H. C., Stone, S. J., Zhou, P., Buhman, K. K., & Farese, R. V. (2002) · Diabetes · doi:10.2337/diabetes.51.11.3189 · Cited by 132 · see citing works
Boden, G., Homko, C., Mozzoli, M., Showe, L. C., Nichols, C., & Cheung, P. (2005) · Diabetes · doi:10.2337/diabetes.54.3.880 · Cited by 129 · see citing works
Intravenous lipid emulsions: removal mechanisms as compared to chylomicrons.
Hultin, M., Carneheim, C., Rosenqvist, K., & Olivecrona, T. (1996) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39201-4 · Cited by 118 · see citing works
Depot-specific differences in adipose tissue gene expression in lean and obese subjects
Lefebvre, A., Laville, M., Vega, N., et al. (1998) · Diabetes · doi:10.2337/diabetes.47.1.98 · Cited by 96 · see citing works
Regional Differences in the Response of Human Pre-Adipocytes to PPARγ and RXRα Agonists
Sewter, C. P., Blows, F. M., Vidal‐Puig, A., & O’Rahilly, S. (2002) · Diabetes · doi:10.2337/diabetes.51.3.718 · Cited by 94 · see citing works
Response of adipose tissue lipoprotein lipase to the cephalic phase of insulin secretion.
Picard, F., Naïmi, N., Richard, D., & Deshaies, Y. (1999) · Diabetes · doi:10.2337/diabetes.48.3.452 · Cited by 83 · see citing works
Self-citationASP enhances in situ lipoprotein lipase activity by increasing fatty acid trapping in adipocytes
Faraj, M., Sniderman, A. D., & Cianflone, K. (2004) · Journal of Lipid Research · doi:10.1194/jlr.m300299-jlr200 · Cited by 75 · see citing works
Differential Expression of PPAR γ1 and γ2 Isoforms in Human Adipose Tissue
Yanase, T., Yashiro, T., Takitani, K., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6446 · Cited by 50 · see citing works
Brito, M. N., Brito, N. A., Brito, S. R. C., et al. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.4.r1003 · Cited by 49 · see citing works
PPAR‐γ2 Expression in Response to Cafeteria Diet: Gender‐ and Depot‐Specific Effects
Rodríguez, E., Ribot, J., Rodríguez, A. M., & Palou, A. (2004) · Obesity Research · doi:10.1038/oby.2004.182 · Cited by 48 · see citing works
Comparison of adipose tissue changes following administration of rosiglitazone in the dog and rat
Toseland, C. D. N., Campbell, S., Francis, I., Bugelski, P. J., & Mehdi, N. (2001) · Diabetes Obesity and Metabolism · doi:10.1046/j.1463-1326.2001.00117.x · Cited by 43 · see citing works
Control of glyceroneogenic activity in rat brown adipose tissue
Festuccia, W. T., Kawashita, N. H., Garófalo, M. A. R., et al. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00713.2002 · Cited by 35 · see citing works
Self-citationPicard, F., Boivin, A., Lalonde, J., & Deshaies, Y. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00307.2001 · Cited by 33 · see citing works
Self-citationCoort, S. L., Coumans, W. A., Bonen, A., Vusse, G. J., Glatz, J. F. C., & Luiken, J. J. F. P. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m400426-jlr200 · Cited by 31 · see citing works
Kalderon, B., Mayorek, N., Ben-Yacov, L., & Bar‐Tana, J. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00368.2002 · Cited by 18 · see citing works
MacDonald, M. J., & Grewe, B. K. (1981) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(81)90216-2 · Cited by 12 · see citing works
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- Authors
- Laplante, M., Festuccia, W. T., Soucy, G., Gélinas, Y., Lalonde, J., Berger, J. P., & Deshaies, Y.
- Affiliations
- Université Laval (CA)
- Laval Hospital Research Centre and Department of Anatomy and Physiology, Faculty of Medicine, Laval University, Quebec, Quebec, Canada
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2006-10-01
- Volume
- 55
- Issue
- 10
- Pages
- 2771-2778
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2114528799
- Cited by
- 119
- References
- 50
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 5 · 2019: 1 · 2018: 3 · 2017: 5 · 2016: 8 · 2015: 3 · 2014: 8 · 2013: 6 · 2012: 8
- FWCI
- 5.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- PPARγ agonism, subcutaneous adipose tissue, visceral fat, fat redistribution, adipose tissue metabolism, lipoprotein lipase, AP-2, diacylglycerol acyltransferase 1, lipolysis, fatty acid oxidation, thermogenesis, mitochondrial biogenesis, energy expenditure, triglyceride esterification
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Uncoupling Protein 1, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, Acetates, Adipose Tissue, Animals, Carnitine O-Palmitoyltransferase, Energy Metabolism, Fatty Acids, Glycerol, Indoles, Ion Channels, Lipolysis, Male, Mitochondria, Protein Kinases, Transcription Factors, RNA-Binding Proteins, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Adipocytes, Mitochondrial Proteins, Acyl-CoA Dehydrogenase, Long-Chain, PPAR gamma, Subcutaneous Fat, Intra-Abdominal Fat, Rats
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