Reader TTS

ABSTRACT OBJECTIVE: Reduced serum adiponectin levels have been found in obesity and type 2 diabetes and variations in the adiponectin gene (_APM1_) have been associated with type 2 diabetes

and features of the metabolic syndrome in different populations. STUDY DESIGN: Here, we investigated the expression of _APM1_ in adipose tissue and studied the relationship between variation

in _APM1_ expression, the _APM1_ G276T polymorphism, the common PPARG Pro12Ala polymorphism and clinical features of 36 morbidly obese (body mass index (BMI) 41.5±4.9 kg/m2) nondiabetic

subjects. RESULTS: _APM1_ mRNA expression in visceral fat was correlated with serum adiponectin levels (_r_=0.54, _P_=0.012). In visceral, but not in subcutaneous, adipose tissue _APM1_ mRNA

level was 38% higher among carriers of the _APM1_ G276T T allele (G/T and T/T) than among carriers of the G/G genotype (0.91±0.06 for G/T and T/T carriers vs 0.66±0.09 for G/G carriers,

_P_=0.013). Carriers of the T allele also had significantly higher body fat percent compared to G/G carriers (65±6 vs 56±10%, _P_=0.011). CONCLUSION: Our results indicate that genetic

variation in _APM1_ influences the expression of the gene in visceral adipose tissue and suggest a potential role for such variation in regulation of body fat accumulation in obese subjects.

Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this

journal Receive 12 print issues and online access $259.00 per year only $21.58 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now

Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer

support SIMILAR CONTENT BEING VIEWED BY OTHERS THE ASSOCIATION BETWEEN VITAMIN D RECEPTOR POLYMORPHISMS AND TISSUE-SPECIFIC INSULIN RESISTANCE IN HUMAN OBESITY Article 20 January 2021

GENETIC VARIATIONS IN ADIPONECTIN LEVELS AND DIETARY PATTERNS ON METABOLIC HEALTH AMONG CHILDREN WITH NORMAL WEIGHT VERSUS OBESITY: THE BCAMS STUDY Article 29 October 2021 IDENTIFICATION OF

CIRCULATING APOLIPOPROTEIN M AS A NEW DETERMINANT OF INSULIN SENSITIVITY AND RELATIONSHIP WITH ADIPONECTIN Article Open access 15 March 2024 REFERENCES * Hotamisligil GS, Arner P, Caro JF,

Atkinson RL, Spiegelman BM . Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. _J Clin Invest_ 1995; 95: 2409–2415. Article  CAS 

Google Scholar  * Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM et al. The hormone resistin links obesity to diabetes. _Nature_ 2001; 409: 307–312. Article  CAS  Google

Scholar  * Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T et al. Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity. _Nat

Med_ 1996; 2: 800–803. Article  CAS  Google Scholar  * Friedman JM, Halaas JL . Leptin and the regulation of body weight in mammals. _Nature_ 1998; 395: 763–770. Article  CAS  Google

Scholar  * Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. _Biochem Biophys Res Commun_

1999; 257: 79–83. Article  CAS  Google Scholar  * Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE et al. Hypoadiponectinemia in obesity and type 2 diabetes: close

association with insulin resistance and hyperinsulinemia. _J Clin Endocrinol Metab_ 2001; 86: 1930–1935. Article  CAS  Google Scholar  * Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H,

Okamoto Y et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. _Circulation_ 1999; 100: 2473–2476. Article  CAS  Google Scholar  * Daimon

M, Oizumi T, Saitoh T, Kameda W, Hirata A, Yamaguchi H et al. Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese Population: the

Funagata study. _Diabetes Care_ 2003; 26: 2015–2020. Article  CAS  Google Scholar  * Tschritter O, Fritsche A, Thamer C, Haap M, Shirkavand F, Rahe S et al. Plasma adiponectin concentrations

predict insulin sensitivity of both glucose and lipid metabolism. _Diabetes_ 2003; 52: 239–243. Article  CAS  Google Scholar  * Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K et al.

Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. _Diabetes_ 2002; 51: 536–540. Article  CAS  Google

Scholar  * Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M et al. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance

syndrome. _Diabetes_ 2002; 51: 2325–2328. Article  CAS  Google Scholar  * Vasseur F, Helbecque N, Dina C, Lobbens S, Delannoy V, Gaget S et al. Single-nucleotide polymorphism haplotypes in

the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians.

_Hum Mol Genet_ 2002; 11: 2607–2614. Article  CAS  Google Scholar  * Populaire C, Mori Y, Dina C, Vasseur F, Vaxillaire M, Kadowaki T et al. Does the -11377 promoter variant of APM1 gene

contribute to the genetic risk for Type 2 diabetes mellitus in Japanese families? _Diabetologia_ 2003; 46: 443–445. Article  CAS  Google Scholar  * Hu FB, Doria A, Li T, Meigs JB, Liu S,

Memisoglu A et al. Genetic variation at the adiponectin locus and risk of type 2 diabetes in women. _Diabetes_ 2004; 53: 209–213. Article  CAS  Google Scholar  * Gu HF, Abulaiti A, Ostenson

CG, Humphreys K, Wahlestedt C, Brookes AJ et al. Single nucleotide polymorphisms in the proximal promoter region of the adiponectin (APM1) gene are associated with type 2 diabetes in Swedish

caucasians. _Diabetes_ 2004; 53 (Suppl 1): S31–S35. Article  CAS  Google Scholar  * Fumeron F, Aubert R, Siddiq A, Betoulle D, Pean F, Hadjadj S et al. Adiponectin gene polymorphisms and

adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study.

_Diabetes_ 2004; 53: 1150–1157. Article  CAS  Google Scholar  * Menzaghi C, Ercolino T, Di Paola R, Berg AH, Warram JH, Scherer PE et al. A haplotype at the adiponectin locus is associated

with obesity and other features of the insulin resistance syndrome. _Diabetes_ 2002; 51: 2306–2312. Article  CAS  Google Scholar  * Menzaghi C, Ercolino T, Salvemini L, Coco A, Kim SH, Fini

G et al. Multigenic control of serum adiponectin levels: evidence for a role of the APM1 gene and a locus on 14q13. _Physiol Genomics_ 2004; 19: 170–174. Article  CAS  Google Scholar  *

Filippi E, Sentinelli F, Trischitta V, Romeo S, Arca M, Leonetti F et al. Association of the human adiponectin gene and insulin resistance. _Eur J Hum Genet_ 2004; 12: 199–205. Article  CAS

  Google Scholar  * Bacci S, Menzaghi C, Ercolino T, Ma X, Rauseo A, Salvemini L et al. The +276 G/T single nucleotide polymorphism of the adiponectin gene is associated with coronary artery

disease in type 2 diabetic patients. _Diabetes Care_ 2004; 27: 2015–2020. Article  CAS  Google Scholar  * Lihn AS, Bruun JM, He G, Pedersen SB, Jensen PF, Richelsen B . Lower expression of

adiponectin mRNA in visceral adipose tissue in lean and obese subjects. _Mol Cell Endocrinol_ 2004; 219: 9–15. Article  CAS  Google Scholar  * Motoshima H, Wu X, Sinha MK, Hardy VE, Rosato

EL, Barbot DJ et al. Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone. _J Clin Endocrinol Metab_

2002; 87: 5662–5667. Article  CAS  Google Scholar  * Ohashi K, Ouchi N, Kihara S, Funahashi T, Nakamura T, Sumitsuji S et al. Adiponectin I164T mutation is associated with the metabolic

syndrome and coronary artery disease. _J Am Coll Cardiol_ 2004; 43: 1195–1200. Article  CAS  Google Scholar  * Yang WS, Tsou PL, Lee WJ, Tseng DL, Chen CL, Peng CC et al. Allele-specific

differential expression of a common adiponectin gene polymorphism related to obesity. _J Mol Med_ 2003; 81: 428–434. Article  CAS  Google Scholar  * Arner P . Regional adipocity in man. _J

Endocrinol_ 1997; 155: 191–192. Article  CAS  Google Scholar  * Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K et al. PPARgamma ligands increase expression and plasma

concentrations of adiponectin, an adipose-derived protein. _Diabetes_ 2001; 50: 2094–2099. Article  CAS  Google Scholar  * Ridderstrale M, Carlsson E, Klannemark M, Cederberg A, Kosters C,

Tornqvist H et al. FOXC2 mRNA Expression and a 5′ untranslated region polymorphism of the gene are associated with insulin resistance. _Diabetes_ 2002; 51: 3554–3560. Article  CAS  Google

Scholar  * Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and

insulin concentrations in man. _Diabetologia_ 1985; 28: 412–419. Article  CAS  Google Scholar  * Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J et al. Association

between adiponectin and mediators of inflammation in obese women. _Diabetes_ 2003; 52: 942–947. Article  CAS  Google Scholar  * Hoffstedt J, Arvidsson E, Sjolin E, Wahlen K, Arner P .

Adipose tissue adiponectin production and adiponectin serum concentration in human obesity and insulin resistance. _J Clin Endocrinol Metab_ 2004; 89: 1391–1396. Article  CAS  Google Scholar

  * Statnick MA, Beavers LS, Conner LJ, Corominola H, Johnson D, Hammond CD et al. Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes.

_Int J Exp Diabetes Res_ 2000; 1: 81–88. Article  CAS  Google Scholar  * Yan H, Yuan W, Velculescu VE, Vogelstein B, Kinzler KW . Allelic variation in human gene expression. _Science_ 2002;

297: 1143. Article  CAS  Google Scholar  * Qiao L, Maclean PS, Schaack J, Orlicky DJ, Darimont C, Pagliassotti M et al. C/EBPalpha regulates human adiponectin gene transcription through an

intronic enhancer. _Diabetes_ 2005; 54: 1744–1754. Article  CAS  Google Scholar  * Kershaw EE, Flier JS . Adipose tissue as an endocrine organ. _J Clin Endocrinol Metab_ 2004; 89: 2548–2556.

Article  CAS  Google Scholar  * Vohl MC, Sladek R, Robitaille J, Gurd S, Marceau P, Richard D et al. A survey of genes differentially expressed in subcutaneous and visceral adipose tissue

in men. _Obes Res_ 2004; 12: 1217–1222. Article  CAS  Google Scholar  * Giusti V, Suter M, Verdumo C, Gaillard RC, Burckhardt P, Pralong FP . Molecular determinants of human adipose tissue:

differences between visceral and subcutaneous compartments in obese women. _J Clin Endocrinol Metab_ 2004; 89: 1379–1384. Article  CAS  Google Scholar  * Swinburn BA, Nyomba BL, Saad MF,

Zurlo F, Raz I, Knowler WC et al. Insulin resistance associated with lower rates of weight gain in Pima Indians. _J Clin Invest_ 1991; 88: 168–173. Article  CAS  Google Scholar  * Yamauchi

T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. _Nat Med_ 2001; 7:

941–946. Article  CAS  Google Scholar  * Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. _Nat

Med_ 2002; 8: 731–737. Article  CAS  Google Scholar  * Shand BI, Scott RS, Elder PA, George PM . Plasma adiponectin in overweight, nondiabetic individuals with or without insulin

resistance. _Diabetes Obes Metab_ 2003; 5: 349–353. Article  CAS  Google Scholar  * Liu YM, Lacorte JM, Viguerie N, Poitou C, Pelloux V, Guy-Grand B et al. Adiponectin gene expression in

subcutaneous adipose tissue of obese women in response to short-term very low calorie diet and refeeding. _J Clin Endocrinol Metab_ 2003; 88: 5881–5886. Article  CAS  Google Scholar  * Hotta

K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity

during the progression to type 2 diabetes in rhesus monkeys. _Diabetes_ 2001; 50: 1126–1133. Article  CAS  Google Scholar  * Lihn AS, Ostergard T, Nyholm B, Pedersen SB, Richelsen B, Schmitz

O . Adiponectin expression in adipose tissue is reduced in first-degree relatives of type 2 diabetic patients. _Am J Physiol Endocrinol Metab_ 2003; 284: E443–E448. Article  CAS  Google

Scholar  * Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G . Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis

factor-alpha expression. _Diabetes_ 2003; 52: 1779–1785. Article  CAS  Google Scholar  * Garaulet M, Viguerie N, Porubsky S, Klimcakova E, Clement K, Langin D et al. Adiponectin gene

expression and plasma values in obese women during very-low-calorie diet. Relationship with cardiovascular risk factors and insulin resistance. _J Clin Endocrinol Metab_ 2004; 89: 756–760.

Article  CAS  Google Scholar  * Milan G, Granzotto M, Scarda A, Calcagno A, Pagano C, Federspil G et al. Resistin and adiponectin expression in visceral fat of obese rats: effect of weight

loss. _Obes Res_ 2002; 10: 1095–1103. Article  CAS  Google Scholar  * Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M et al. Induction of adiponectin, a fat-derived

antidiabetic and antiatherogenic factor, by nuclear receptors. _Diabetes_ 2003; 52: 1655–1663. Article  CAS  Google Scholar  * Altshuler D, Hirschhorn JN, Klannemark M, Lindgren CM, Vohl MC,

Nemesh J et al. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. _Nat Genet_ 2000; 26: 76–80. Article  CAS  Google Scholar  * Yamamoto Y,

Hirose H, Miyashita K, Nishikai K, Saito I, Taniyama M et al. PPAR(gamma)2 gene Pro12Ala polymorphism may influence serum level of an adipocyte-derived protein, adiponectin, in the Japanese

population. _Metabolism_ 2002; 51: 1407–1409. Article  CAS  Google Scholar  * Thamer C, Machicao F, Fritsche A, Stumvoll M, Haring H . No influence of the PPARgamma2 Pro12Ala genotype on

serum adiponectin concentrations in healthy Europeans. _Metabolism_ 2003; 52: 798; author reply 98–99. Article  CAS  Google Scholar  * Kolehmainen M, Uusitupa MI, Alhava E, Laakso M, Vidal H

. Effect of the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor (PPAR) gamma2 gene on the expression of PPARgamma target genes in adipose tissue of massively obese

subjects. _J Clin Endocrinol Metab_ 2003; 88: 1717–1722. Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS This work was supported by Grants from the Foundation for

Strategic Research through the National Network for Cardiovascular Research, the Swedish Foundation for the Study of Diabetes, the Albert Påhlssons Foundation, the Swedish Medical Research

Council, Malmö University Hospital Foundation, the Ernhold Lundström Foundation, the Anna-Lisa and Sven-Eric Lundgren Foundation, the Crafoord Foundation, the Lundberg Foundation, the Magnus

Bergvall Foundation, the Fredrik and Ingrid Thurings Foundation, the Novo Nordisk Foundation and the European Association for the Study of Diabetes (Sankyo Pharma). AUTHOR INFORMATION

AUTHORS AND AFFILIATIONS * Department of Clinical Sciences/Diabetes and Endocrinology, Malmö University Hospital, Lund University, Wallenberg Laboratory, Malmö, Sweden J Fredriksson, E

Carlsson, M Orho-Melander, L Groop & M Ridderstråle Authors * J Fredriksson View author publications You can also search for this author inPubMed Google Scholar * E Carlsson View author

publications You can also search for this author inPubMed Google Scholar * M Orho-Melander View author publications You can also search for this author inPubMed Google Scholar * L Groop View

author publications You can also search for this author inPubMed Google Scholar * M Ridderstråle View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHOR Correspondence to J Fredriksson. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Fredriksson, J., Carlsson, E., Orho-Melander, M.

_et al._ A polymorphism in the adiponectin gene influences adiponectin expression levels in visceral fat in obese subjects. _Int J Obes_ 30, 226–232 (2006).

https://doi.org/10.1038/sj.ijo.0803138 Download citation * Received: 23 March 2005 * Revised: 30 August 2005 * Accepted: 12 September 2005 * Published: 11 October 2005 * Issue Date: 01

February 2006 * DOI: https://doi.org/10.1038/sj.ijo.0803138 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a

shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * adiponectin * _APM1_ * adipose

tissue * gene expression