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Horm Metab Res 2006; 38(8): 486-490
DOI: 10.1055/s-2006-949520
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Adiponectin Expression is Paradoxically Increased in Gold-thioglucose-induced Obesity

P. Huypens 1 , E. Quartier 1
  • 1Diabetes Research Center (Partner of the Juvenile Diabetes Research Center for Beta Cell Therapy in Europe), Brussels Free University - VUB, Brussels, Belgium
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Publikationsverlauf

Received 27 September 2005

Accepted after revision 2 February 2006

Publikationsdatum:
29. August 2006 (online)

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Abstract

Following the chemically-induced lesion of the ventromedial nucleus, gold-thioglucose treated rodents display hypothalamic leptin resistance, hyperphagia, hyperinsulinemia and obesity. Despite the exuberant hyperinsulinemia following gold-thioglucose treatment, systemic insulin sensitivity is preserved during the early phase of the obesity syndrome, resulting in extensive fat production and markedly increased leptin levels. Leptin and adiponectin levels are inversely associated in vivo. However, the reciprocal relationship between leptin and adiponectin can not be explained by in vitro observations, suggesting the involvement of the central nervous system. We measured leptin and adiponectin expression levels in gold-thioglucose obese and control mice. In this study, we show that gold-thioglucose treatment causes a profound reduction in the number of hypothalamic glucokinase transcripts in rodents. Also, we demonstrate that the adiponectin expression levels and protein content are increased in gold-thioglucose treated animals, which can explain the increased insulin sensitivity during the early phase of the obesity syndrome. Furthermore, as the increased leptin production in gold-thioglucose obese mice is not paralleled by reduced adiponectin production, our data suggest that the inverse regulation between leptin and adiponectin levels is, at least partially, mediated via the hypothalamus.

Key words

Adipokines - leptin - hypothalamus - adipose tissue - insulin sensitivity

References

  • 1 Debons AF, Krimsky I, Maayan ML, Fani K, Jemenez FA. Gold thioglucose obesity syndrome.  Fed Proc. 1977;  36 143-147
    PubMedSuche in Google Scholar
  • 2 Blair SC, Caterson ID, Cooney GJ. Insulin response to an intravenous glucose load during development of obesity in gold thioglucose-injected mice.  Diabetes. 1993;  42 1153-1158
    PubMedSuche in Google Scholar
  • 3 Blair SC, Caterson ID, Cooney GJ. Insulin response to a spontaneously ingested standard meal during the development of obesity in GTG-injected mice.  Int J Obes Relat Metab Disord. 1996;  20 319-323
    PubMedSuche in Google Scholar
  • 4 Fei H, Okano HJ, Li C, Lee GH, Zhao C, Darnell R, Friedman JM. Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues.  Proc Natl Acad Sci USA. 1997;  94 7001-7005
    CrossrefPubMedSuche in Google Scholar
  • 5 Satoh N, Ogawa Y, Katsuura G, Tsuji T, Masuzaki H, Hiraoka J, Okazaki T, Tamaki M, Hayase M, Yoshimasa Y, Nishi S, Hosoda K, Nakao K. Pathophysiological significance of the obese gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats: evidence for loss of its satiety effect in VMH-lesioned rats.  Endocrinology. 1997;  138 947-954
    CrossrefPubMedSuche in Google Scholar
  • 6 Bryson JM, Phuyal JL, Swan V, Caterson ID. Leptin has acute effects on glucose and lipid metabolism in both lean and gold thioglucose-obese mice.  Am J Physiol. 1999;  277 417-422
    PubMedSuche in Google Scholar
  • 7 Bryson JM, Phuyal JL, Proctor DR, Blair SC, Caterson ID, Cooney GJ. Plasma insulin rise precedes rise in ob mRNA expression and plasma leptin in gold thioglucose-obese mice.  Am J Physiol. 1999;  276 358-364
    PubMedSuche in Google Scholar
  • 8 Le Marchand Y, Freychet P, Jeanrenaud B. Longitudinal study on the establishment of insulin resistance in hypothalamic obese mice.  Endocrinology. 1978;  102 74-85
    PubMedSuche in Google Scholar
  • 9 Penicaud L, Kinebanyan MF, Ferre P, Morin J, Kande J, Smadja C, Marfaing-Jallat P, Picon L. Development of VMH obesity: in vivo insulin secretion and tissue insulin sensitivity.  Am J Physiol. 1989;  257 255-260
    PubMedSuche in Google Scholar
  • 10 Blair SC, Cooney GJ, Denyer GS, Williams PF, Caterson ID. Differences in lipogenesis in tissues of control and gold-thioglucose obese mice after an isocaloric meal.  Biochim Biophys Acta. 1991;  1085 385-388
    PubMedSuche in Google Scholar
  • 11 Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.  Nat Med. 2001;  7 941-946
    CrossrefPubMedSuche in Google Scholar
  • 12 Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.  J Clin Endocrinol Metab. 2001;  86 1930-1935
    CrossrefPubMedSuche in Google Scholar
  • 13 Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients.  Arterioscler Thromb Vasc Biol. 2000;  20 1595-1599
    CrossrefPubMedSuche in Google Scholar
  • 14 Hotta K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC, Matsuzawa Y. 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
    PubMedSuche in Google Scholar
  • 15 Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity.  J Biol Chem. 1996;  271 10697-106703
    CrossrefPubMedSuche in Google Scholar
  • 16 Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.  Biochem Biophys Res Commun. 1999;  257 79-83
    CrossrefPubMedSuche in Google Scholar
  • 17 Fisher FM, McTernan PG, Valsamakis G, Chetty R, Harte AL, Anwar AJ, Starcynski J, Crocker J, Barnett AH, McTernan CL, Kumar S. Differences in adiponectin protein expression: effect of fat depots and type 2 diabetic status.  Horm Metab Res. 2002;  34 650-654
    Thieme ConnectPubMedSuche in Google Scholar
  • 18 Matsubara M, Maruoka S, Katayose S. Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women.  Eur J Endocrinol. 2002;  147 173-180
    CrossrefPubMedSuche in Google Scholar
  • 19 Inoue M, Maehata E, Yano M, Taniyama M, Suzuki S. Correlation between the adiponectin-leptin ratio and parameters of insulin resistance in patients with type 2 diabetes.  Metabolism. 2005;  54 281-286
    CrossrefPubMedSuche in Google Scholar
  • 20 Havel PJ. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin.  Curr Opin Lipidol. 2002;  13 51-59
    CrossrefPubMedSuche in Google Scholar
  • 21 Zhang Y, Matheny M, Zolotukhin S, Tumer N, Scarpace PJ. Regulation of adiponectin and leptin gene expression in white and brown adipose tissues: influence of beta3-adrenergic agonists, retinoic acid, leptin and fasting.  Biochim Biophys Acta. 2002;  1584 115-122
    PubMedSuche in Google Scholar
  • 22 Atzmon G, Yang XM, Muzumdar R, Ma XH, Gabriely I, Barzilai N. Differential gene expression between visceral and subcutaneous fat depots.  Horm Metab Res. 2002;  34 622-628
    Thieme ConnectPubMedSuche in Google Scholar
  • 23 Ueno N, Dube MG, Inui A, Kalra PS, Kalra SP. Leptin modulates orexigenic effects of ghrelin, attenuates adiponectin and insulin levels, and selectively the dark-phase feeding as revealed by central leptin gene therapy.  Endocrinology. 2004;  145 4176-4184
    CrossrefPubMedSuche in Google Scholar
  • 24 Heimberg H, Bouwens L, Heremans Y, Van De Casteele M, Lefebvre V, Pipeleers D. Adult human pancreatic duct and islet cells exhibit similarities in expression and differences in phosphorylation and complex formation of the homeodomain protein Ipf-1.  Diabetes. 2000;  49 571-579
    PubMedSuche in Google Scholar
  • 25 Herberg L, Coleman DL. Laboratory animals exhibiting obesity and diabetes syndromes.  Metabolism. 1977;  26 59-99
    CrossrefPubMedSuche in Google Scholar
  • 26 Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, Uchida S, Ito Y, Takakuwa K, Matsui J, Takata M, Eto K, Terauchi Y, Komeda K, Tsunoda M, Murakami K, Ohnishi Y, Naitoh T, Yamamura K, Ueyama Y, Froguel P, Kimura S, Nagai R, Kadowaki T. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis.  J Biol Chem. 2003;  278 2461-2468
    CrossrefPubMedSuche in Google Scholar
  • 27 Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N, Inaba T, Funahashi T, Matsuzawa Y. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice.  Circulation. 2002;  106 2767-2770
    CrossrefPubMedSuche in Google Scholar
  • 28 Lyngdorf LG, Gregersen S, Daugherty A, Falk E. Paradoxical reduction of atherosclerosis in apoe-deficient mice with obesity-related type 2 diabetes.  Cardiovasc Res. 2003;  59 854-862
    CrossrefPubMedSuche in Google Scholar
  • 29 Haynes WG, Morgan DA, Walsh SA, Mark AL, Sivitz WI. Receptor-mediated regional sympathetic nerve activation by leptin.  J Clin Invest. 1997;  100 270-278
    CrossrefPubMedSuche in Google Scholar
  • 30 Kappes A, Loffler G. Influences of ionomycin, dibutyryl-cycloAMP and tumour necrosis factor-alpha on intracellular amount and secretion of apM1 in differentiating primary human preadipocytes.  Horm Metab Res. 2000;  32 548-554
    PubMedSuche in Google Scholar
  • 31 Nowak L, Adamczak M, Wiecek A. Blockade of sympathetic nervous system activity by rilmenidine increases plasma adiponectin concentration in patients with essential hypertension.  Am J Hypertens. 2005;  18 1470-1475
    CrossrefPubMedSuche in Google Scholar

Correspondence

P. Huypens

Diabetes Research Center·Vrije Universiteit Brussel

Laarbeeklaan 103·1090 Brussels·Belgium

Telefon: +32/2/477 44 71

Fax: +32/2/477 44 72

eMail: Peter.Huypens@vub.ac.be