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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2006-1465
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The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 2 720-724
Copyright © 2007 by The Endocrine Society

BRIEF REPORT

Effects of Chronic Rosiglitazone Therapy on Gene Expression in Human Adipose Tissue in Vivo in Patients with Type 2 Diabetes

Maria Kolak, Hannele Yki-Järvinen, Katja Kannisto, Mirja Tiikkainen, Anders Hamsten, Per Eriksson and Rachel M. Fisher

Atherosclerosis Research Unit (M.K., K.K., A.H., P.E., R.M.F.), King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden; Department of Medicine (H.Y.-J., M.T.), Division of Diabetes, University of Helsinki, 00029 Helsinki, Finland; and Minerva Institute for Medical Research (H.Y.-J.), 00290 Helsinki, Finland

Address all correspondence and requests for reprints to: Rachel M. Fisher, Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital M1:01, 171 76 Stockholm, Sweden. E-mail: rachel.fisher{at}ki.se.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Objective: The aim of this study was to compare effects of therapeutic doses of rosiglitazone and metformin on expression of 50 genes in human adipose tissue in vivo.

Methods: Twenty patients with diet-treated type 2 diabetes (13 women, seven men) were randomized to receive either rosiglitazone (n = 9; 8 mg/d) or metformin (n = 11; 2 g/d) for 16 wk. Subcutaneous adipose tissue biopsies were performed before and after treatment. Expression of 50 genes, previously shown to be altered by thiazolidinediones in experimental models, was quantified by real-time PCR and normalized to two housekeeping genes.

Results: Rosiglitazone, but not metformin, treatment increased expression of genes involved in triacylglycerol storage [e.g. stearyl-CoA desaturase (3.2-fold), CD36 (1.8-fold)], structural genes [e.g. {alpha}-1 type-1 procollagen (1.7-fold) and GLUT4 (1.5-fold)], and decreased expression of inflammation-related genes [e.g. IL-6 (0.6-fold), chemokine (C-C motif) ligand 3 (0.4-fold)], 11ß-hydroxysteroid dehydrogenase 1 (0.6-fold), and resistin (0.3-fold) (all P < 0.05).

Conclusions: These results suggest that the insulin-sensitizing action of rosiglitazone involves remodeling of human adipose tissue to reduce inflammation and promote lipid storage. Furthermore, we show some important differences between thiazolidinedione action in human adipose tissue and experimental models.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
ROSIGLITAZONE, ONE OF the thiazolidinedione (TZD) class of antidiabetic drugs, is an agonist for peroxisome proliferator activated receptor-{gamma} (PPAR{gamma}), a nuclear receptor predominantly expressed in adipose tissue (1). Rosiglitazone increases insulin sensitivity both in liver and peripheral tissues (1). Metformin is believed to act primarily in liver via activation of AMP-activated protein kinase. Both metformin and rosiglitazone increase hepatic insulin sensitivity, but only the latter reduces liver fat content (2).

Although numerous studies have investigated TZD effects on gene expression in cultured adipocytes and white adipose tissue of rodents, data from human adipose tissue are very limited. This paucity of human data are particularly important because pharmacological doses, exceeding therapeutic doses by 100-fold, have been used in experimental models (3, 4). Effects of TZDs in 3T3-L1 cells and rodent white adipose tissue include regulation of genes involved in fatty acid metabolism, inflammation, apoptosis, control of cell growth, and other pathways (3, 4, 5, 6, 7, 8, 9). These actions of TZDs are often considered valid also in human adipose tissue, although many have not been confirmed or even investigated in humans. Indeed, the expression of a very restricted number of genes has been quantified in human studies (10, 11, 12). In the present study we systematically reviewed literature regarding TZD actions on gene expression in animal models and/or cultured adipocytes and selected 50 genes shown to be regulated by TZDs in these systems using supraphysiological doses. We examined long-term effects of therapeutic doses of rosiglitazone on expression of these genes in human sc adipose tissue in patients with type 2 diabetes. Patients treated with metformin served as controls.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Twenty diet-treated type 2 diabetes patients (13 women, seven men; age 48 ± 3 yr, body mass index 31 ± 1 kg/m2), not on medication, were randomized in a double-blind fashion to either rosiglitazone (n = 9; 3 male/6 female, 8 mg/d) or metformin (n = 11; 4 male/7 female, 2 g/d) for 16 wk, as described (2). Blood samples and adipose tissue biopsies were taken before and after treatment. Total RNA and cDNA from adipose tissue were prepared as described (2). Serum concentrations of IL-6, resistin, and chemokine (C-C motif) ligand 3 (CCL3) were measured using Human Quantikine ELISA Kits (R&D Systems, Minneapolis, MN). The nature and potential risks of the study were explained to all subjects before obtaining written informed consent. The study was approved by the ethics committees of Helsinki University Hospital and Karolinska Institutet.

Selection of genes for analysis was performed by means of literature search for genes whose expression has previously been shown to be altered by TZDs in white adipose tissue of rodents or cultured adipocytes. In addition, genes whose expression in adipose tissue is believed to be related to insulin resistance or obesity were investigated. mRNA expression was quantified by real-time PCR using ABI 7000 SDS instrument (Applied Biosystems, Foster City, CA), using cDNA synthesized from 15 ng of total RNA in a final volume of 15 µl. The selected genes (n = 50) plus two housekeeping genes (TATA-box binding protein and ribosomal protein large P0) and assays used are listed in Table 1Go.


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  		TABLE 1. Genes selected for quantification

 
Statview (SAS Institute Inc., Cary, NC) software was used for statistical analysis. Expression levels are in arbitrary units and normalized relative to the housekeeping genes ribosomal protein large P0 and TATA-box binding protein. These two values were averaged and fold changes of gene expression after treatment (relative to baseline levels) calculated for each subject. Correlations were calculated using Spearman’s rank correlation coefficient. Comparison of variables before and after treatment was performed with paired t test. Statistical significance was assigned to P < 0.05.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Both rosiglitazone and metformin improved hepatic insulin sensitivity in these patients with type 2 diabetes and decreased glucose, insulin, and non-esterified fatty acid concentrations. Clinical characterization of the patients and effects of this treatment have been reported (2). Body weight decreased by 2.4 ± 0. 9 kg (P < 0.05) in the metformin group and remained unchanged by rosiglitazone (+0.6 ± 0.7 kg, not significant). Unlike metformin, rosiglitazone also improved insulin clearance and peripheral insulin sensitivity and reduced liver fat content (2).

Effects of rosiglitazone and metformin on mRNA expression levels of 50 genes in sc adipose tissue were determined (Table 2Go). Genes significantly up-regulated by rosiglitazone were stearyl-CoA desaturase (SCD; 3.2-fold), CD36 (1.4-fold), fatty acid synthase (FASN; 2.0-fold), {alpha}-1 type 1 procollagen (COL1A1; 1.7-fold), fibronectin (FN1; 1.5-fold), cell death activator C (CIDEC; 1.5-fold), and GLUT4 (1.5-fold). Genes significantly down-regulated were resistin (RETN; 0.28-fold), CCL3 (0.37-fold), IL-6 (0.62-fold), 11ß-hydroxysteroid dehydrogenase 1 (11ßHSD1; 0.55-fold), fatty acid transport protein 1 (FATP1; 0.79-fold), and GLUT1 (0.67-fold). Only adipsin showed a significant change (decrease) in expression after metformin treatment. Adiponectin, lipoprotein lipase, and PPAR{gamma} expression were shown previously to increase after rosiglitazone, but not metformin treatment (2).


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  		TABLE 2. Fold changes of gene expression levels in sc adipose tissue from patients with type 2 diabetes after 16 wk of either rosiglitazone or metformin treatment

 
To investigate whether rosiglitazone-induced changes in adipokine gene expression in adipose tissue were accompanied by changes in circulating concentrations, serum resistin, IL-6, and CCL3 were determined. Serum resistin decreased after treatment with rosiglitazone (7.8 ± 1.2 vs. 6.8 ± 0.9 ng/ml, n = 9; P = 0.03) but was unchanged by metformin (6.5 ± 0.5 vs. 6.0 ± 0.5 ng/ml, n = 11). There were no significant changes in serum IL-6 in either rosiglitazone or metformin groups (0.68 ± 0.11 vs. 0.67 ± 0.12 pg/ml, n = 9, and 0.67 ± 0.10 vs. 0.60 ± 0.06 pg/ml, n = 9, respectively). Serum CCL3 concentrations were below the assay’s detection limit.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
We quantified gene expression in sc adipose tissue in patients with type 2 diabetes before and after treatment with rosiglitazone or metformin. Rosiglitazone altered expression of genes involved in fatty acid synthesis and storage, structural proteins, macrophage-related and inflammation-related genes and genes involved in glucose transport and insulin sensitivity. None of these genes were affected by metformin.

TZD-induced changes in expression of genes involved in fatty acid uptake, metabolism, and triacylglycerol synthesis in rodents and cell lines (4, 5, 6, 8, 9) are similar to our and other results in humans (10, 11, 15). Of all the genes, SCD was the most up-regulated by rosiglitazone. SCD is proposed to play a critical role in the generation of body fat because mice lacking SCD are protected against obesity (16). The increase in SCD by rosiglitazone in adipose tissue may therefore have contributed to the increase in body weight relative to metformin in the present study. Expression of the SCD homolog SCD4 was unaffected by rosiglitazone, indicating a specific effect on SCD expression rather than a general effect on {Delta}9-desaturases. TZD-induced increases in SCD and CD36 expression have also been reported in human skeletal muscle, although the latter was not statistically significant (11). One exception to the apparent coordinated up-regulation of genes involved in triacylglycerol storage in adipose tissue was the rosiglitazone-induced down-regulation of FATP1. This novel finding in human adipose tissue is contrary to previous findings in rodents (9).

The expression of genes encoding structural proteins FN1 and COL1A1 increased in adipose tissue after rosiglitazone. The increase in expression of genes promoting fat storage could be related to adipose tissue growth and thereby increased demand for structural protein synthesis. TZDs increased COL1A1 expression in murine white adipose tissue (5), but decreased FN1 in 3T3-L1 adipocytes (4). Our data are the first to our knowledge to show up-regulation of these genes by a TZD in human adipose tissue.

Insulin resistance is associated with low-grade inflammation and macrophage accumulation within adipose tissue (13). Reducing this inflammation may be an important step in improving insulin sensitivity in type 2 diabetes. In the present study there was decreased expression of inflammatory markers in adipose tissue, implying that inflammation in adipose tissue is related to insulin resistance and not just to obesity. Decreases in CCL3 and IL-6 expression are consistent with previous rodent data (13), but novel in demonstrating such changes with therapeutic doses of rosiglitazone in patients. In contrast to adipose tissue mRNA levels, circulating IL-6 concentrations remained unchanged by rosiglitazone. Because only a small fraction of circulating IL-6 originates from adipose tissue (17), circulating IL-6 may be regulated by changes in IL-6 expression in other tissues. TZD treatment increases resistin expression in 3T3-L1 cells (6), contrary to our findings in diabetic patients. In humans, resistin is highly expressed in macrophages rather than adipocytes (18). Decreased resistin mRNA levels could be explained by a rosiglitazone-mediated decrease in inflammation and reduction in macrophage number or activation in adipose tissue. Serum resistin concentrations were also decreased by rosiglitazone, but not by metformin.

Rosiglitazone-mediated increases in adipose tissue CIDEC expression have been seen in some studies involving murine white adipose tissue (4, 5, 9), but not previously in humans. CIDEC has apoptosis-inducing activity (19) that might be involved in remodeling of adipose tissue through removal of macrophages. Indeed, pioglitazone induced macrophage apoptosis in adipose tissue in individuals with impaired glucose tolerance (20).

Rosiglitazone, but not metformin, increased peripheral insulin mediated glucose uptake in the present study (2). Because GLUT4 is rate-limiting for insulin-stimulated glucose uptake, increased adipose tissue GLUT4 gene expression may play a role in rosiglitazone’s insulin-sensitizing action. Furthermore, a tendency toward a rosiglitazone-mediated increase in GLUT4 expression in human skeletal muscle has been reported (10). Contrary to increased GLUT4 and decreased GLUT1 expression in our study, rosiglitazone increased GLUT1, but not GLUT4 expression in 3T3-L1 cells (9). This adaptation is typical for cultured cells continually exposed to glucose in their culture media. Such differences highlight the importance of studying human adipose tissue in vivo. Furthermore, inhibition of 11ßHSD1 expression by PPAR{gamma} agonists has been shown in 3T3-L1 adipocytes (3), but our study is the first to our knowledge to demonstrate it in human adipose tissue. However, no such effect was observed in patients with type 2 diabetes after 12 wk of pioglitazone (12).

Many genes analyzed in the current study showed no significant change in expression after either rosiglitazone or metformin, despite selection based on previous studies. This may be due to the fact that almost all such studies were performed in rodent adipose tissue or an adipocyte cell line and not in human adipose tissue in vivo. Importantly, in rodent studies (3, 4), the rosiglitazone dose was 10 mg/kg·d, approximately 100-fold higher than therapeutic doses used in humans. Moreover, genes affected by TZDs in rodents are not necessarily similarly regulated in humans. For example, carbonic anhydrase 3 protein increased 2-fold after rosiglitazone treatment in mice (7), whereas we saw no increase in carbonic anhydrase 3 mRNA in human adipose tissue. Also, the ß3 adrenogenic receptor gene was up-regulated 23-fold by TZD in one study (6), but down-regulated 6-fold in another (4), although both studies used 3T3-L1 adipocytes. In the present study ß3 adrenogenic receptor gene expression remained unchanged.

In summary, we investigated effects of therapeutic doses of rosiglitazone on expression of a large number of genes in human adipose tissue in vivo. Our data suggest that coincident to improved insulin sensitivity, rosiglitazone coordinately regulates adipose tissue gene expression to promote lipid storage and decrease inflammation. Also, we show that although there are similarities in TZD-induced improvements in insulin sensitivity, there may be substantial differences in mechanisms of TZD action between experimental models and humans.


   Acknowledgments
 
We thank Katja Tuominen and Mia Urjansson for technical assistance and Sari Mäkimattila for clinical expertise.


   Footnotes
 
Current address for K.K.: Department of Surgery, Akerhus University Hospital, 1478 Lørenskog, Oslo, Norway.

This work was supported by grants from Biovitrum (H.Y.-J., A.H., P.E., R.M.F.), the Swedish Research Council (R.M.F.; project 15352), the Swedish Diabetes Association (R.M.F.), the Novo Nordisk Foundation (R.M.F.), the Loo and Hans Osterman Foundation (R.M.F.), Karolinska Institutet (A.H.), and the Stockholm County Council (A.H.).

First Published Online December 5, 2006

Abbreviations: CCL3, Chemokine (c-c motif) ligand 3; TZD, thiazolidinedione; PPAR{gamma}, peroxisome proliferator activated receptor-{gamma}.

Received July 7, 2006.

Accepted November 22, 2006.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Yki-Jarvinen H 2004 Thiazolidinediones. N Engl J Med 351:1106–1118[Free Full Text]
  2. Tiikkainen M, Hakkinen AM, Korsheninnikova E, Nyman T, Makimattila S, Yki-Jarvinen H 2004 Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes 53:2169–2176[Abstract/Free Full Text]
  3. Berger J, Tanen M, Elbrecht A, Hermanowski-Vosatka A, Moller DE, Wright SD, Thieringer R 2001 Peroxisome proliferator-activated receptor-{gamma} ligands inhibit adipocyte 11ß-hydroxysteroid dehydrogenase type 1 expression and activity. J Biol Chem 276:12629–12635[Abstract/Free Full Text]
  4. Gerhold DL, Liu F, Jiang G, Li Z, Xu J, Lu M, Sachs JR, Bagchi A, Fridman A, Holder DJ, Doebber TW, Berger J, Elbrecht A, Moller DE, Zhang BB 2002 Gene expression profile of adipocyte differentiation and its regulation by peroxisome proliferator-activated receptor-{gamma} agonists. Endocrinology 143:2106–2118[Abstract/Free Full Text]
  5. Albrektsen T, Frederiksen KS, Holmes WE, Boel E, Taylor K, Fleckner J 2002 Novel genes regulated by the insulin sensitizer rosiglitazone during adipocyte differentiation. Diabetes 51:1042–1051[Abstract/Free Full Text]
  6. Li Y, Lazar MA 2002 Differential gene regulation by PPAR{gamma} agonist and constitutively active PPAR{gamma}2. Mol Endocrinol 16:1040–1048[Abstract/Free Full Text]
  7. Sanchez JC, Converset V, Nolan A, Schmid G, Wang S, Heller M, Sennitt MV, Hochstrasser DF, Cawthorne MA 2003 Effect of rosiglitazone on the differential expression of obesity and insulin resistance associated proteins in lep/lep mice. Proteomics 3:1500–1520[CrossRef][Medline]
  8. Singh Ahuja H, Liu S, Crombie DL, Boehm M, Leibowitz MD, Heyman RA, Depre C, Nagy L, Tontonoz P, Davies PJ 2001 Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents. Mol Pharmacol 59:765–773[Abstract/Free Full Text]
  9. Wellen KE, Uysal KT, Wiesbrock S, Yang Q, Chen H, Hotamisligil GS 2004 Interaction of tumor necrosis factor-{alpha}- and thiazolidinedione-regulated pathways in obesity. Endocrinology 145:2214–2220[Abstract/Free Full Text]
  10. Tan GD, Fielding BA, Currie JM, Humphreys SM, Desage M, Frayn KN, Laville M, Vidal H, Karpe F 2005 The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes. Diabetologia 48:83–95[CrossRef][Medline]
  11. Tonelli J, Li W, Kishore P, Pajvani UB, Kwon E, Weaver C, Scherer PE, Hawkins M 2004 Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes. Diabetes 53:1621–1629[Abstract/Free Full Text]
  12. Bogacka I, Xie H, Bray GA, Smith SR 2004 The effect of pioglitazone on peroxisome proliferator-activated receptor-{gamma} target genes related to lipid storage in vivo. Diabetes Care 27:1660–1667[Abstract/Free Full Text]
  13. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H 2003 Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830[CrossRef][Medline]
  14. Sutinen J, Kannisto K, Korsheninnikova E, Fisher RM, Ehrenborg E, Nyman T, Virkamaki A, Funahashi T, Matsuzawa Y, Vidal H, Hamsten A, Yki-Jarvinen H 2004 Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy. Am J Physiol Endocrinol Metab 286:E941–E949
  15. Riserus U, Tan GD, Fielding BA, Neville MJ, Currie J, Savage DB, Chatterjee VK, Frayn KN, O’Rahilly S, Karpe F 2005 Rosiglitazone increases indexes of stearoyl-CoA desaturase activity in humans: link to insulin sensitization and the role of dominant-negative mutation in peroxisome proliferator-activated receptor-{gamma}. Diabetes 54:1379–1384[Abstract/Free Full Text]
  16. Ntambi JM, Miyazaki M, Stoehr JP, Lan H, Kendziorski CM, Yandell BS, Song Y, Cohen P, Friedman JM, Attie AD 2002 Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci USA 99:11482–11486[Abstract/Free Full Text]
  17. Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW 1997 Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-{alpha}, in vivo. J Clin Endocrinol Metab 82:4196–4200[Abstract/Free Full Text]
  18. Patel L, Buckels AC, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA 2003 Resistin is expressed in human macrophages and directly regulated by PPAR{gamma} activators. Biochem Biophys Res Commun 300:472–476[CrossRef][Medline]
  19. Liang L, Zhao M, Xu Z, Yokoyama KK, Li T 2003 Molecular cloning and characterization of CIDE-3, a novel member of the cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector family. Biochem J 370:195–203[CrossRef][Medline]
  20. Bodles AM, Varma V, Yao-Borengasser A, Phanavanh B, Peterson CA, McGehee Jr RE, Rasouli N, Wabitsch M, Kern PA 2006 Pioglitazone induces apoptosis of macrophages in human adipose tissue. J Lipid Res 47:2080–2088[Abstract/Free Full Text]



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