Diabetes, Vol 47, Issue 9 1384-1391, Copyright © 1998 by American Diabetes Association

ARTICLES

Depot-related gene expression in human subcutaneous and omental adipocytes

CT Montague, JB Prins, L Sanders, J Zhang, CP Sewter, J Digby, CD Byrne and S O'Rahilly
Department of Medicine, University of Cambridge, England, UK. carl.montague@alderley.zeneca.com

Human omental adipocytes display a range of biochemical properties that distinguish them from adipocytes of subcutaneous origin. However, information about site-related gene expression in human fat cells is limited. We have previously demonstrated that leptin mRNA is markedly overexpressed in abdominal subcutaneous (SC) compared with omental (Om) adipocytes. To further investigate depot-specific differences in adipocyte gene expression, we have measured, in paired samples of isolated human adipocytes obtained from SC and Om fat depots, the expression of mRNAs encoding a number of proteins involved in the control of adipocyte metabolism. In contrast to the marked site-related expression of leptin, genes encoding lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), tumor necrosis factor-alpha (TNF-alpha), and adipsin were not consistently differentially expressed. Of note, a highly significant inverse correlation between adipocyte PPAR-gamma expression and BMI (r = -0.7, P = 0.0005) was found. In parallel experiments, differential display was used in an attempt to identify novel and/or unexpected adipocyte genes that were expressed in a site-related manner. No transcript that was unique to one or another depot was found, but cellular inhibitor of apoptosis protein-2 (cIAP2) mRNA, which has not previously been reported in adipocytes, was expressed at higher levels in Om than SC adipocytes (Om > SC in all eight subjects; mean Om:SC ratio 1.9 +/- 0.2, P < 0.01). Because cIAP2 may be involved in the regulation of TNF-alpha signaling, this raises the possibility that depot-specific differences may exist in the regulation of adipocyte apoptosis. Thus, of the mRNAs examined to date, only leptin and cIAP2 show consistent site-related expression, suggesting that these molecules may have important roles in determining functional properties particular to individual adipose depots. Given the importance of PPAR-gamma in adipocyte development and insulin sensitivity, the inverse correlation between adipocyte PPAR-gamma mRNA levels and adiposity may represent a local regulatory mechanism restraining fat accumulation and/or may be related to the reduction of insulin sensitivity that occurs with increasing fat mass.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B.-S. Youn, N. Kloting, J. Kratzsch, N. Lee, J. W. Park, E.-S. Song, K. Ruschke, A. Oberbach, M. Fasshauer, M. Stumvoll, et al. Serum Vaspin Concentrations in Human Obesity and Type 2 Diabetes Diabetes, February 1, 2008; 57(2): 372 - 377. [Abstract] [Full Text] [PDF]

				H. Shi, A. D. Strader, S. C. Woods, and R. J. Seeley The effect of fat removal on glucose tolerance is depot specific in male and female mice Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E1012 - E1020. [Abstract] [Full Text] [PDF]

				P. Balagopal, T. E. Graham, B. B. Kahn, A. Altomare, V. Funanage, and D. George Reduction of Elevated Serum Retinol Binding Protein in Obese Children by Lifestyle Intervention: Association with Subclinical Inflammation J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1971 - 1974. [Abstract] [Full Text] [PDF]

				J. V. Silha, B.L. G. Nyomba, W. D. Leslie, and L. J. Murphy Ethnicity, Insulin Resistance, and Inflammatory Adipokines in Women at High and Low Risk for Vascular Disease Diabetes Care, February 1, 2007; 30(2): 286 - 291. [Abstract] [Full Text] [PDF]

				T. Tchkonia, M. Lenburg, T. Thomou, N. Giorgadze, G. Frampton, T. Pirtskhalava, A. Cartwright, M. Cartwright, J. Flanagan, I. Karagiannides, et al. Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E298 - E307. [Abstract] [Full Text] [PDF]

				J.-M. Ategbo, O. Grissa, A. Yessoufou, A. Hichami, K. L. Dramane, K. Moutairou, A. Miled, A. Grissa, M. Jerbi, Z. Tabka, et al. Modulation of Adipokines and Cytokines in Gestational Diabetes and Macrosomia J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4137 - 4143. [Abstract] [Full Text] [PDF]

				M. Laplante, W. T. Festuccia, G. Soucy, Y. Gelinas, J. Lalonde, J. P. Berger, and Y. Deshaies Mechanisms of the Depot Specificity of Peroxisome Proliferator-Activated Receptor {gamma} Action on Adipose Tissue Metabolism. Diabetes, October 1, 2006; 55(10): 2771 - 2778. [Abstract] [Full Text] [PDF]

				T. Tchkonia, N. Giorgadze, T. Pirtskhalava, T. Thomou, M. DePonte, A. Koo, R. A. Forse, D. Chinnappan, C. Martin-Ruiz, T. von Zglinicki, et al. Fat Depot-Specific Characteristics Are Retained in Strains Derived From Single Human Preadipocytes Diabetes, September 1, 2006; 55(9): 2571 - 2578. [Abstract] [Full Text] [PDF]

				D. Gardan, F. Gondret, and I. Louveau Lipid metabolism and secretory function of porcine intramuscular adipocytes compared with subcutaneous and perirenal adipocytes Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E372 - E380. [Abstract] [Full Text] [PDF]

				Y. Bottcher, D. Teupser, B. Enigk, J. Berndt, N. Kloting, M. R. Schon, J. Thiery, M. Bluher, M. Stumvoll, and P. Kovacs Genetic Variation in the Visfatin Gene (PBEF1) and Its Relation to Glucose Metabolism and Fat-Depot-Specific Messenger Ribonucleic Acid Expression in Humans J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2725 - 2731. [Abstract] [Full Text] [PDF]

				J. Berndt, N. Kloting, S. Kralisch, P. Kovacs, M. Fasshauer, M. R. Schon, M. Stumvoll, and M. Bluher Plasma Visfatin Concentrations and Fat Depot-Specific mRNA Expression in Humans Diabetes, October 1, 2005; 54(10): 2911 - 2916. [Abstract] [Full Text] [PDF]

				M. F. Allan, E. J. Eisen, and D. Pomp Genomic Mapping of Direct and Correlated Responses to Long-Term Selection for Rapid Growth Rate in Mice Genetics, August 1, 2005; 170(4): 1863 - 1877. [Abstract] [Full Text] [PDF]

				X. Ding, N. K. Saxena, S. Lin, A. Xu, S. Srinivasan, and F. A. Anania The Roles of Leptin and Adiponectin: A Novel Paradigm in Adipocytokine Regulation of Liver Fibrosis and Stellate Cell Biology Am. J. Pathol., June 1, 2005; 166(6): 1655 - 1669. [Abstract] [Full Text] [PDF]

				D. Hishikawa, Y.-H. Hong, S.-g. Roh, H. Miyahara, Y. Nishimura, A. Tomimatsu, H. Tsuzuki, C. Gotoh, M. Kuno, K.-C. Choi, et al. Identification of genes expressed differentially in subcutaneous and visceral fat of cattle, pig, and mouse Physiol Genomics, May 11, 2005; 21(3): 343 - 350. [Abstract] [Full Text] [PDF]

				F. H. Einstein, G. Atzmon, X.-m. Yang, X.-H. Ma, M. Rincon, E. Rudin, R. Muzumdar, and N. Barzilai Differential Responses of Visceral and Subcutaneous Fat Depots to Nutrients Diabetes, March 1, 2005; 54(3): 672 - 678. [Abstract] [Full Text] [PDF]

				T. Tchkonia, Y. D. Tchoukalova, N. Giorgadze, T. Pirtskhalava, I. Karagiannides, R. A. Forse, A. Koo, M. Stevenson, D. Chinnappan, A. Cartwright, et al. Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E267 - E277. [Abstract] [Full Text] [PDF]

				B. J. Nicklas, B. W. J. H. Penninx, M. Cesari, S. B. Kritchevsky, A. B. Newman, A. M. Kanaya, M. Pahor, D. Jingzhong, and T. B. Harris Association of Visceral Adipose Tissue with Incident Myocardial Infarction in Older Men and Women: The Health, Aging and Body Composition Study Am. J. Epidemiol., October 15, 2004; 160(8): 741 - 749. [Abstract] [Full Text] [PDF]

				Y. Miyazaki, A. Mahankali, E. Wajcberg, M. Bajaj, L. J. Mandarino, and R. A. DeFronzo Effect of Pioglitazone on Circulating Adipocytokine Levels and Insulin Sensitivity in Type 2 Diabetic Patients J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4312 - 4319. [Abstract] [Full Text] [PDF]

				J. W. Tomlinson, J. S. Moore, P. M. S. Clark, G. Holder, L. Shakespeare, and P. M. Stewart Weight Loss Increases 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Expression in Human Adipose Tissue J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2711 - 2716. [Abstract] [Full Text] [PDF]

				N. M. Morton, J. M. Paterson, H. Masuzaki, M. C. Holmes, B. Staels, C. Fievet, B. R. Walker, J. S. Flier, J. J. Mullins, and J. R. Seckl Novel Adipose Tissue-Mediated Resistance to Diet-Induced Visceral Obesity in 11{beta}-Hydroxysteroid Dehydrogenase Type 1-Deficient Mice Diabetes, April 1, 2004; 53(4): 931 - 938. [Abstract] [Full Text] [PDF]

				M. H. Gillis, S. K. Duckett, J. R. Sackmann, C. E. Realini, D. H. Keisler, and T. D. Pringle Effects of supplemental rumen-protected conjugated linoleic acid or linoleic acid on feedlot performance, carcass quality, and leptin concentrations in beef cattle J Anim Sci, March 1, 2004; 82(3): 851 - 859. [Abstract] [Full Text] [PDF]

				H. Bays, L. Mandarino, and R. A. DeFronzo Role of the Adipocyte, Free Fatty Acids, and Ectopic Fat in Pathogenesis of Type 2 Diabetes Mellitus: Peroxisomal Proliferator-Activated Receptor Agonists Provide a Rational Therapeutic Approach J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 463 - 478. [Full Text] [PDF]

				E. H. Johanson, P.-A. Jansson, L. Lonn, Y. Matsuzawa, T. Funahashi, M.-R. Taskinen, U. Smith, and M. Axelsen Fat Distribution, Lipid Accumulation in the Liver, and Exercise Capacity Do Not Explain the Insulin Resistance in Healthy Males with a Family History for Type 2 Diabetes J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4232 - 4238. [Abstract] [Full Text] [PDF]

				M. I. Goran, G. D. C. Ball, and M. L. Cruz Obesity and Risk of Type 2 Diabetes and Cardiovascular Disease in Children and Adolescents J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1417 - 1427. [Abstract] [Full Text] [PDF]

				M. Kolehmainen, M. I. J. Uusitupa, E. Alhava, M. Laakso, and H. Vidal Effect of the Pro12Ala Polymorphism in the Peroxisome Proliferator-Activated Receptor (PPAR) {gamma}2 Gene on the Expression of PPAR{gamma} Target Genes in Adipose Tissue of Massively Obese Subjects J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1717 - 1722. [Abstract] [Full Text] [PDF]

				I. K. Aronson and V. C. Fiedler Of Mice and Men: The Road to Understanding the Complex Nature of Adipose Tissue and Lipoatrophy Arch Dermatol, January 1, 2003; 139(1): 81 - 83. [Full Text] [PDF]

				Y. Miyazaki, L. Glass, C. Triplitt, E. Wajcberg, L. J. Mandarino, and R. A. DeFronzo Abdominal fat distribution and peripheral and hepatic insulin resistance in type 2 diabetes mellitus Am J Physiol Endocrinol Metab, December 1, 2002; 283(6): E1135 - E1143. [Abstract] [Full Text] [PDF]

				C. Sewter, F. Blows, R. Considine, A. Vidal-Puig, and S. O'Rahilly Differential Effects of Adiposity on Peroxisomal Proliferator-Activated Receptor {gamma}1 and {gamma}2 Messenger Ribonucleic Acid Expression in Human Adipocytes J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4203 - 4207. [Abstract] [Full Text] [PDF]

				D. Dietze, M. Koenen, K. Rohrig, H. Horikoshi, H. Hauner, and J. Eckel Impairment of Insulin Signaling in Human Skeletal Muscle Cells by Co-Culture With Human Adipocytes Diabetes, August 1, 2002; 51(8): 2369 - 2376. [Abstract] [Full Text] [PDF]

				D. B. Savage, C. P. Sewter, E. S. Klenk, D. G. Segal, A. Vidal-Puig, R. V. Considine, and S. O'Rahilly Resistin / Fizz3 Expression in Relation to Obesity and Peroxisome Proliferator-Activated Receptor-{gamma} Action in Humans Diabetes, October 1, 2001; 50(10): 2199 - 2202. [Abstract] [Full Text]

				C. J. de Souza, M. Eckhardt, K. Gagen, M. Dong, W. Chen, D. Laurent, and B. F. Burkey Effects of Pioglitazone on Adipose Tissue Remodeling Within the Setting of Obesity and Insulin Resistance Diabetes, August 1, 2001; 50(8): 1863 - 1871. [Abstract] [Full Text] [PDF]

				M. Caron, M. Auclair, C. Vigouroux, M. Glorian, C. Forest, and J. Capeau The HIV Protease Inhibitor Indinavir Impairs Sterol Regulatory Element-Binding Protein-1 Intranuclear Localization, Inhibits Preadipocyte Differentiation, and Induces Insulin Resistance Diabetes, June 1, 2001; 50(6): 1378 - 1388. [Abstract] [Full Text]

				C. D. Russell, M. R. Ricci, R. E. Brolin, E. Magill, and S. K. Fried Regulation of the leptin content of obese human adipose tissue Am J Physiol Endocrinol Metab, March 1, 2001; 280(3): E399 - E404. [Abstract] [Full Text] [PDF]

				B. L. Wajchenberg Subcutaneous and Visceral Adipose Tissue: Their Relation to the Metabolic Syndrome Endocr. Rev., December 1, 2000; 21(6): 697 - 738. [Abstract] [Full Text]

				N. Zeghari, H. Vidal, M. Younsi, O. Ziegler, P. Drouin, and M. Donner Adipocyte membrane phospholipids and PPAR-gamma expression in obese women: relationship to hyperinsulinemia Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E736 - E743. [Abstract] [Full Text] [PDF]

				A. M. Isidori, F. Strollo, M. Morè, M. Caprio, A. Aversa, C. Moretti, G. Frajese, G. Riondino, and A. Fabbri Leptin and Aging: Correlation with Endocrine Changes in Male and Female Healthy Adult Populations of Different Body Weights J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1954 - 1962. [Abstract] [Full Text]

				Z. Orban, A. T. Remaley, M. Sampson, Z. Trajanoski, and G. P. Chrousos The Differential Effect of Food Intake and {beta}-Adrenergic Stimulation on Adipose-Derived Hormones and Cytokines in Man J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2126 - 2133. [Abstract] [Full Text]

				B. I. Frohnert, T. Y. Hui, and D. A. Bernlohr Identification of a Functional Peroxisome Proliferator-responsive Element in the Murine Fatty Acid Transport Protein Gene J. Biol. Chem., February 12, 1999; 274(7): 3970 - 3977. [Abstract] [Full Text] [PDF]

				S. Tartare-Deckert, C. Chavey, M.-N. Monthouel, N. Gautier, and E. Van Obberghen The Matricellular Protein SPARC/Osteonectin as a Newly Identified Factor Up-regulated in Obesity J. Biol. Chem., June 15, 2001; 276(25): 22231 - 22237. [Abstract] [Full Text] [PDF]