Download PDF
Horm Metab Res 2010; 42(11): 787-791
DOI: 10.1055/s-0030-1262854
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Modulation of IGFBP2 mRNA Expression in White Adipose Tissue upon Aging and Obesity

Z. Li1 , F. Picard1
  • 1Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Québec, QC, Canada G1V 4G5
Further Information

Publication History

received 19.03.2010

accepted 12.07.2010

Publication Date:
20 August 2010 (online)

Also available at
    Permissions and Reprints

Abstract

The insulin/IGF-1 signaling pathway is a determinant of aging and age-related diseases. IGF-binding protein 2 (IGFBP2) is secreted by white adipocytes and contributes to the prevention of diet-induced obesity and age-related insulin resistance in mice. However, the expression levels of IGFBP2 in insulin resistance disorders have not been evaluated. The present study was aimed at determining IGFBP2 mRNA levels in adipose tissue in conditions of insulin resistance such as aging and obesity. In visceral white adipose tissue (WAT), but not in subcutaneous WAT, IGFBP2 mRNA levels were significantly lower in obese ob/ob, db/db and high fat-fed mice compared with those of their respective lean and chow-fed littermates. IGFBP2 mRNA levels were also decreased in visceral WAT of 12 and 24 months old mice compared with those of their 4 months old counterparts. Visceral WAT IGFBP2 expression was significantly associated with IGFBP2 circulating levels in mice, suggesting an important contribution from this tissue. The negative effect of aging on IGFBP2 mRNA levels in visceral WAT was confirmed in obese men. These findings demonstrate that the transcription of the IGFBP2 gene is modulated in a depot-specific fashion in obesity and aging in mice and men. Because IGFBP2 is an adipokine, an altered production from visceral WAT depots could impact on IGF-1 signaling and its downstream targets. This supports the need for further molecular and clinical studies to determine the factors regulating IGFBP2 expression and its relevance to metabolicdiseases.

Key words

IGFBP2 - IGF-1 - mice - men - mRNA - plasma - insulin signaling

References

  • 1 Elahi D, Muller DC. Carbohydrate metabolism in the elderly.  Eur J Clin Nutr. 2000;  54 (S 03) S112-S120
    Google Scholar
  • 2 Reaven GM, Chen N, Hollenbeck C, Chen YD. Effect of age on glucose tolerance and glucose uptake in healthy individuals.  J Am Geriatr Soc. 1989;  37 735-740
    Google Scholar
  • 3 Blaak EE. Adrenergically stimulated fat utilization and ageing.  Ann Med. 2000;  32 380-382
    Google Scholar
  • 4 Bravo E, Rivabene R, Bruscalupi G, Calcabrini A, Arancia G, Cantafora A. Age-related changes in lipid secretion of perfused livers from male Wistar rats donors.  J Biochem (Tokyo). 1996;  119 240-245
    Google Scholar
  • 5 Gupta G, Cases JA, She L, Ma XH, Yang XM, Hu M, Wu J, Rossetti L, Barzilai N. Ability of insulin to modulate hepatic glucose production in aging rats is impaired by fat accumulation.  Am J Physiol. 2000;  278 E985-E991
    Google Scholar
  • 6 Imbeault P, Prins JB, Stolic M, Russell AW, O’Moore-Sullivan T, Despres JP, Bouchard C, Tremblay A. Aging per se does not influence glucose homeostasis.  Diabetes Care. 2003;  26 480-484
    Google Scholar
  • 7 Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW, Berg AH, Scherer P, Rossetti L, Barzilai N. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process?.  Diabetes. 2002;  51 2951-2958
    Google Scholar
  • 8 Cartier A, Cote M, Lemieux I, Perusse L, Tremblay A, Bouchard C, Despres JP. Age-related differences in inflammatory markers in men: contribution of visceral adiposity.  Metabolism. 2009;  58 1452-1458
    Google Scholar
  • 9 Caldwell JD, Jirikowski GF. Sex hormone binding globulin and aging.  Horm Metab Res. 2009;  41 173-182
    Google Scholar
  • 10 Nogalska A, Stelmanska E, Sledzinski T, Swierczynski J. Surgical removal of perirenal and epididymal adipose tissue decreases serum leptin concentration and increases lipogenic enzyme activities in remnant adipose tissue of old rats.  Gerontology. 2009;  55 224-228
    Google Scholar
  • 11 Koh SJ, Hyun YJ, Choi SY, Chae JS, Kim JY, Park S, Ahn CM, Jang Y, Lee JH. Influence of age and visceral fat area on plasma adiponectin concentrations in women with normal glucose tolerance.  Clin Chim Acta. 2008;  389 45-50
    Google Scholar
  • 12 Arafat AM, Weickert MO, Frystyk J, Spranger J, Schofl C, Mohlig M, Pfeiffer AF. The role of insulin-like growth factor (IGF) binding protein-2 in the insulin-mediated decrease in IGF-I bioactivity.  J Clin Endocrinol Metab. 2009;  94 5093-5101
    Google Scholar
  • 13 Wheatcroft SB, Kearney MT. IGF-dependent and IGF-independent actions of IGF-binding protein-1 and -2: implications for metabolic homeostasis.  Trends Endocrinol Metab. 2009;  20 153-162
    Google Scholar
  • 14 Hill DJ, Hogg J, Petrik J, Arany E, Han VK. Cellular distribution and ontogeny of insulin-like growth factors (IGFs) and IGF binding protein messenger RNAs and peptides in developing rat pancreas.  J Endocrinol. 1999;  160 305-317
    Google Scholar
  • 15 DeMambro VE, Clemmons DR, Horton LG, Bouxsein ML, Wood TL, Beamer WG, Canalis E, Rosen CJ. Gender-specific changes in bone turnover and skeletal architecture in igfbp-2-null mice.  Endocrinology. 2008;  149 2051-2061
    Google Scholar
  • 16 Wood AW, Schlueter PJ, Duan C. Targeted knockdown of insulin-like growth factor binding protein-2 disrupts cardiovascular development in zebrafish embryos.  Mol Endocrinol. 2005;  19 1024-1034
    Google Scholar
  • 17 Degraff DJ, Malik M, Chen Q, Miyako K, Rejto L, Aguiar AA, Bancroft DR, Cohen P, Sikes RA. Hormonal regulation of IGFBP-2 proteolysis is attenuated with progression to androgen insensitivity in the LNCaP progression model.  J Cell Physiol. 2007;  213 261-268
    Google Scholar
  • 18 Miyako K, Cobb LJ, Francis M, Huang A, Peng B, Pintar JE, Ariga H, Cohen P. PAPA-1 is a nuclear binding partner of IGFBP-2 and modulates its growth-promoting actions.  Mol Endocrinol. 2009;  23 169-175
    Google Scholar
  • 19 Fornoni A, Rosenzweig SA, Lenz O, Rivera A, Striker GE, Elliot SJ. Low insulin-like growth factor binding protein-2 expression is responsible for increased insulin receptor substrate-1 phosphorylation in mesangial cells from mice susceptible to glomerulosclerosis.  Endocrinology. 2006;  147 3547-3554
    Google Scholar
  • 20 Albiston AL, Herington AC. Tissue distribution and regulation of insulin-like growth factor (IGF)-binding protein-3 messenger ribonucleic acid (mRNA) in the rat: comparison with IGF-I mRNA expression.  Endocrinology. 1992;  130 497-502
    Google Scholar
  • 21 Gosteli-Peter MA, Winterhalter KH, Schmid C, Froesch ER, Zapf J. Expression and regulation of insulin-like growth factor-I (IGF-I) and IGF-binding protein messenger ribonucleic acid levels in tissues of hypophysectomized rats infused with IGF-I and growth hormone.  Endocrinology. 1994;  135 2558-2567
    Google Scholar
  • 22 Boney CM, Moats-Staats BM, Stiles AD, D’Ercole AJ. Expression of insulin-like growth factor-I (IGF-I) and IGF-binding proteins during adipogenesis.  Endocrinology. 1994;  135 1863-1868
    Google Scholar
  • 23 Wheatcroft SB, Kearney MT, Shah AM, Ezzat VA, Miell JR, Modo M, Williams SC, Cawthorn WP, Medina-Gomez G, Vidal-Puig A, Sethi JK, Crossey PA. IGF-binding protein-2 protects against the development of obesity and insulin resistance.  Diabetes. 2007;  56 285-294
    Google Scholar
  • 24 Hoeflich A, Wu M, Mohan S, Foll J, Wanke R, Froehlich T, Arnold GJ, Lahm H, Kolb HJ, Wolf E. Overexpression of insulin-like growth factor-binding protein-2 in transgenic mice reduces postnatal body weight gain.  Endocrinology. 1999;  140 5488-5496
    Google Scholar
  • 25 Hedbacker K, Birsoy K, Wysocki RW, Asilmaz E, Ahima RS, Farooqi IS, Friedman JM. Antidiabetic effects of IGFBP2, a leptin-regulated gene.  Cell Metab. 2010;  11 11-22
    Google Scholar
  • 26 Lukanova A, Soderberg S, Stattin P, Palmqvist R, Lundin E, Biessy C, Rinaldi S, Riboli E, Hallmans G, Kaaks R. Nonlinear relationship of insulin-like growth factor (IGF)-I and IGF-I/IGF-binding protein-3 ratio with indices of adiposity and plasma insulin concentrations (Sweden).  Cancer Causes Control. 2002;  13 509-516
    Google Scholar
  • 27 Martin RM, Holly JM, Davey Smith G, Gunnell D. Associations of adiposity from childhood into adulthood with insulin resistance and the insulin-like growth factor system: 65-year follow-up of the Boyd Orr Cohort.  J Clin Endocrinol Metab. 2006;  91 3287-3295
    Google Scholar
  • 28 Nam SY, Lee EJ, Kim KR, Cha BS, Song YD, Lim SK, Lee HC, Huh KB. Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone.  Int J Obes Relat Metab Disord. 1997;  21 355-359
    Google Scholar
  • 29 Heald AH, Kaushal K, Siddals KW, Rudenski AS, Anderson SG, Gibson JM. Insulin-like growth factor binding protein-2 (IGFBP-2) is a marker for the metabolic syndrome.  Exp Clin Endocrinol Diabetes. 2006;  114 371-376
    Google Scholar
  • 30 Mattsson A, Svensson D, Schuett B, Osterziel KJ, Ranke MB. Multidimensional reference regions for IGF-I, IGFBP-2 and IGFBP-3 concentrations in serum of healthy adults.  Growth Horm IGF Res. 2008;  18 506-516
    Google Scholar
  • 31 Clemmons DR, Snyder DK, Busby Jr WH. Variables controlling the secretion of insulin-like growth factor binding protein-2 in normal human subjects.  J Clin Endocrinol Metab. 1991;  73 727-733
    Google Scholar
  • 32 Miard S, Dombrowski L, Carter S, Boivin L, Picard F. Aging alters PPARgamma in rodent and human adipose tissue by modulating the balance in steroid receptor coactivator-1.  Aging Cell. 2009;  8 449-459
    Google Scholar
  • 33 Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome.  Nature. 2006;  444 881-887
    Google Scholar
  • 34 Muzumdar R, Allison DB, Huffman DM, Ma X, Atzmon G, Einstein FH, Fishman S, Poduval AD, McVei T, Keith SW, Barzilai N. Visceral adipose tissue modulates mammalian longevity.  Aging Cell. 2008;  7 438-440
    Google Scholar
  • 35 Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, Cervera P, Le Bouc Y. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice.  Nature. 2003;  421 182-187
    Google Scholar
  • 36 Rincon M, Rudin E, Barzilai N. The insulin/IGF-1 signaling in mammals and its relevance to human longevity.  Exp Gerontol. 2005;  40 873-877
    Google Scholar
  • 37 Arnqvist HJ. The role of IGF-system in vascular insulin resistance.  Horm Metab Res. 2008;  40 588-592
    Google Scholar
  • 38 Miard S, Picard F. Obesity and aging have divergent genomic fingerprints.  Int J Obes (Lond). 2008;  32 1873-1874
    Google Scholar
  • 39 Blüher M, Kahn BB, Kahn CR. Extended longevity in mice lacking the insulin receptor in adipose tissue.  Science. 2003;  299 572-574
    Google Scholar
  • 40 Chiu CH, Lin WD, Huang SY, Lee YH. Effect of a C/EBP gene replacement on mitochondrial biogenesis in fat cells.  Genes Dev. 2004;  18 1970-1975
    Google Scholar
  • 41 Heikkinen S, Argmann C, Feige JN, Koutnikova H, Champy MF, Dali-Youcef N, Schadt EE, Laakso M, Auwerx J. The Pro12Ala PPARgamma2 variant determines metabolism at the gene-environment interface.  Cell Metab. 2009;  9 88-98
    Google Scholar
  • 42 Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI, Claret M, Al-Qassab H, Carmignac D, Ramadani F, Woods A, Robinson IC, Schuster E, Batterham RL, Kozma SC, Thomas G, Carling D, Okkenhaug K, Thornton JM, Partridge L, Gems D, Withers DJ. Ribosomal protein S6 kinase 1 signaling regulates mammalian life span.  Science. 2009;  326 140-144
    Google Scholar
  • 43 Harrison DE, Archer JR, Astle CM. Effects of food restriction on aging: separation of food intake and adiposity.  Proc Natl Acad Sci USA. 1984;  81 1835-1838
    Google Scholar
  • 44 Combs TP, Berg AH, Rajala MW, Klebanov S, Iyengar P, Jimenez-Chillaron JC, Patti ME, Klein SL, Weinstein RS, Scherer PE. Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin.  Diabetes. 2003;  52 268-276
    Google Scholar
  • 45 Misso ML, Jang C, Adams J, Tran J, Murata Y, Bell R, Boon WC, Simpson ER, Davis SR. Differential expression of factors involved in fat metabolism with age and the menopause transition.  Maturitas. 2005;  51 299-306
    Google Scholar
  • 46 Adamczak M, Rzepka E, Chudek J, Wiecek A. Ageing and plasma adiponectin concentration in apparently healthy males and females.  Clin Endocrinol (Oxf). 2005;  62 114-118
    Google Scholar
  • 47 Isobe T, Saitoh S, Takagi S, Takeuchi H, Chiba Y, Katoh N, Shimamoto K. Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study.  Eur J Endocrinol. 2005;  153 91-98
    Google Scholar

Correspondence

F. Picard

Institut universitaire de

cardiologie et de pneumologie

de Québec (IUCPQ)

Y3106 Pavillon Marguerited’Youville

2725 Chemin Ste-Foy

Québec, QC G1V 4G5

Canada

Phone: +1/418/656 8711 ext.: 3737

Fax: +1/418/656 4942

Email: Frederic.Picard@criucpq.ulaval.ca

      >