Adiponectin Oligomers in Human Serum during Acute and Chronic Exercise: Relation to Lipid Metabolism and Insulin Sensitivity

Abstract

Beneficial effects of physical exercise include improved insulin sensitivity, which may be affected by a modulated release of adiponectin, which is exclusively synthesized in white adipose tissue and mediates insulin sensitivity. Adiponectin circulates in three different oligomers, which also have a distinct biological function. We therefore aimed to investigate the distribution of adiponectin oligomers in human serum in relation to physical activity. Thirty-eight lean and healthy individuals were investigated. Seven healthy women and 8 healthy men volunteered to investigate the effect of chronic exercise, at 3 different time points with different training intensities. These individuals were all highly trained and were compared to a control group with low physical activity (n = 15). For studying acute exercise effects, 8 healthy men participated in a bicycle test. Adiponectin was determined by ELISA, oligomers were detected by non-denaturating western blot. Total adiponectin and oligomers were unchanged by acute exercise. LDL cholesterol was significantly lower in the chronic exercise group (p = 0.03). Total adiponectin levels and oligomers were not different between these two groups and were unaltered by different training intensities. However, total adiponectin and specifically HMW oligomers correlated with HDL cholesterol (r = 0.459; p = 0.009). We conclude that acute and chronic exercise does not directly affect circulating adiponectin or oligomer distribution in lean and healthy individuals. Whether such regulation is relevant in individuals with a metabolic disorder remains to be determined. However, our data suggest that adiponectin oligomers have distinct physiological functions in vivo, and specifically HMW adiponectin is closely correlated with HDL cholesterol.

Key words

Exercise - adiponectin - obesity - lipids - insulin sensitivity

References

• 1 Berg A H, Combs T P, Du X, Brownlee M, Scherer P E. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action.  Nat Med. 2001;  7 947-953
• 2 Bobbert T, Rochlitz H, Wegewitz U, Akpulat S, Mai K, Weickert M O, Mohlig M, Pfeiffer A F, Spranger J. Changes of adiponectin oligomer composition by moderate weight reduction.  Diabetes. 2005;  54 2712-2719
• 3 Byberg L, Zethelius B, McKeigue P M, Lithell H O. Changes in physical activity are associated with changes in metabolic cardiovascular risk factors.  Diabetologia. 2001;  44 2134-2139
• 4 Chan D C, Watts G F, Ng T W, Uchida Y, Sakai N, Yamashita S, Barrett P H. adiponectin and other adipocytokines as predictors of markers of triglyceride-rich lipoprotein metabolism.  Clin Chem. 2005;  51 578-585
• 5 Eriksson K F, Lindgarde F. No excess 12-year mortality in men with impaired glucose tolerance who participated in the Malmo Preventive Trial with diet and exercise.  Diabetologia. 1998;  41 1010-1016
• 6 Ferguson M A, White L J, McCoy S, Kim H W, Petty T, Wilsey J. Plasma adiponectin response to acute exercise in healthy subjects.  Eur J Appl Physiol. 2004;  91 324-329
• 7 Havel P J. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin.  Curr Opin Lipidol. 2002;  13 51-59
• 8 Helmrich S P, Ragland D R, Leung R W, Paffenbarger Jr R S. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus.  N Engl J Med. 1991;  325 147-152
• 9 Hu E, Liang P, Spiegelman B M. AdipoQ is a novel adipose-specific gene dysregulated in obesity.  J Biol Chem. 1996;  271 10697-10703
• 10 Hulver M W, Zheng D, Tanner C J, Houmard J A, Kraus W E, Slentz C A, Sinha M K, Pories W J, MacDonald K G, Dohm G L. Adiponectin is not altered with exercise training despite enhanced insulin action.  Am J Physiol. 2002;  283 E861-E865
• 11 Jurimae J, Purge P, Jurimae T. Adiponectin is altered after maximal exercise in highly trained male rowers.  Eur J Appl Physiol. 2005;  93 502-505
• 12 Kirwan J P, del Aguila L F. Insulin signalling, exercise and cellular integrity.  Biochem Soc Trans. 2003;  31 1281-1285
• 13 Kraemer R R, Aboudehen K S, Carruth A K, Durand R T, Acevedo E O, Hebert E P, Johnson L G, Castracane V D. Adiponectin responses to continuous and progressively intense intermittent exercise.  Med Sci Sports Exerc. 2003;  35 1320-1325
• 15 Kriketos A D, Gan S K, Poynten A M, Furler S M, Chisholm D J, Campbell L V. Exercise increases adiponectin levels and insulin sensitivity in humans.  Diabetes Care. 2004;  27 629-630
• 16 Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, Eto K, Yamashita T, Kamon J, Satoh H, Yano W, Froguel P, Nagai R, Kimura S, Kadowaki T, Noda T. Disruption of adiponectin causes insulin resistance and neointimal formation.  J Biol Chem. 2002;  277 25863-25866
• 17 Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1).  Biochem Biophys Res Commun. 1996;  221 286-289
• 18 Nakano Y, Tobe T, Choi-Miura N H, Mazda T, Tomita M. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma.  J Biochem. 1996;  120 803-812
• 19 Pajvani U B, Hawkins M, Combs T P, Rajala M W, Doebber T, Berger J P, Wagner J A, Wu M, Knopps A, Xiang A H, Utzschneider K M, Kahn S E, Olefsky J M, Buchanan T A, Scherer P E. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity.  J Biol Chem. 2004;  279 12152-12162
• 20 Scherer P E, Williams S, Fogliano M, Baldini G, Lodish H F. A novel serum protein similar to C1q, produced exclusively in adipocytes.  J Biol Chem. 1995;  270 26746-26749
• 21 Schulze M B, Shai I, Rimm E B, Li T, Rifai N, Hu F B. Adiponectin and future coronary heart disease events among men with type 2 diabetes.  Diabetes. 2005;  54 534-539
• 22 Shapiro L, Scherer P E. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor.  Curr Biol. 1998;  8 335-338
• 23 Thompson P D, Crouse S F, Goodpaster B, Kelley D, Moyna N, Pescatello L. The acute versus the chronic response to exercise.  Med Sci Sports Exerc. 2001;  33 S438-S445
• 24 Tomas E, Kelly M, Xiang X, Tsao T S, Keller C, Keller P, Luo Z, Lodish H, Saha A K, Unger R, Ruderman N B. Metabolic and hormonal interactions between muscle and adipose tissue.  Proc Nutr Soc. 2004;  63 381-385
• 25 Tonelli J, Li W, Kishore P, Pajvani U B, Kwon E, Weaver C, Scherer P E, Hawkins M. Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes.  Diabetes. 2004;  53 1621-1629
• 26 Tsao T S, Murrey H E, Hug C, Lee D H, Lodish H F. Oligomerization state-dependent activation of NF-kappa B signaling pathway by adipocyte complement-related protein of 30 kDa (Acrp30).  J Biol Chem. 2002;  277 29359-29362
• 27 Tsao T S, Tomas E, Murrey H E, Hug C, Lee D H, Ruderman N B, Heuser J E, Lodish H F. Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways.  J Biol Chem. 2003;  278 50810-50817
• 28 Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S, Hara K, Hada Y, Vasseur F, Froguel P, Kimura S, Nagai R, Kadowaki T. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin.  J Biol Chem. 2003;  278 40352-40363
• 29 Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley R E, Tataranni P A. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.  J Clin Endocrinol Metab. 2001;  86 1930-1935
• 30 Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno N H, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.  Nature. 2003;  423 762-769
• 31 Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn B B, Kadowaki T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase.  Nat Med. 2002;  8 1288-1295
• 32 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 M L, 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
• 33 Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner A J, Tomiyama Y, Matsuzawa Y. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.  Blood. 2000;  96 1723-1732
• 34 Yokoyama H, Emoto M, Araki T, Fujiwara S, Motoyama K, Morioka T, Koyama H, Shoji T, Okuno Y, Nishizawa Y. Effect of aerobic exercise on plasma adiponectin levels and insulin resistance in type 2 diabetes.  Diabetes Care. 2004;  27 1756-1758
• 35 Yuan M, Konstantopoulos N, Lee J, Hansen L, Li Z W, Karin M, Shoelson S E. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta.  Science. 2001;  293 1673-1677
• 36 Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J M. Positional cloning of the mouse obese gene and its human homologue.  Nature. 1994;  372 425-432