Relationship between Serum Adiponectin Concentration and Intramyocellular Lipid Stores in Humans

Abstract

The recently identified adipocytokine adiponectin has been shown to improve insulin action and decrease triglyceride content in skeletal muscle (by stimulating lipid oxidation) in mice. In the present study, we tested the hypothesis that high serum concentrations of adiponectin are associated with lower intramyocellular (IMCL) fat content by promoting lipid oxidation in humans. IMCL-content in predominantly non-oxidative tibialis anterior muscle and oxidative soleus was determined by proton magnetic resonance spectroscopy in a cross- sectional study involving 63 healthy volunteers. In a second set of experiments, changes in IMCL in both muscles were measured after a three days dietary lipid challenge (n = 18) and after intravenous lipid challenge (n = 12) with suppressed lipid oxidation under hyperinsulinemia. Adiponectin serum concentrations were found to be negatively correlated with IMCL in the oxidative soleus muscle (IMCL [sol]) (r = - 0.46, p < 0.001) independent of measures of obesity, but not with IMCL in the non-oxidative tibialis anterior muscle (IMCL [tib]) (p = 0.40). Adiponectin serum concentrations were negatively correlated with the observed increase in IMCL load after dietary lipid challenge in the tibialis (r = 0.53, p = 0.03) but not in the soleus muscle. During suppression of lipid oxidation by hyperinsulinemia, no effect of adiponectin on IMCL was observed in either soleus or tibialis muscle. Overall, the presented findings are consistent with the hypothesis that adiponectin promotes lipid oxidation in humans resulting in lower intracellular lipid content in human muscle. These results are consistent with animal data, where adiponectin could be shown to enhance lipid oxidation and reduce muscle triglycerides.

Key words

Adiponectin - Intramyocellular Fat - Type 2 Diabetes - Insulin Resistance - Obesity

References

• 1 Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Die 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
• 2 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
• 3 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
• 4 Balletshofer B M, Rittig K, Volk A, Maerker E, Jacob S, Rett K, Haring H. Impaired non-esterified fatty acid suppression is associated with endothelial dysfunction in insulin resistant subjects.  Horm Metab Res. 2001;  33 428-431
• 5 Kelley D E, Mandarino L J. Fuel selection in human skeletal muscle in insulin resistance: a reexamination.  Diabetes. 2000;  49 677-683
• 6 Schick F, Machann J, Brechtel K, Strempfer A, Klumpp B, Stein D T, Jacob S. MRI of muscular fat.  Magn Reson Med. 2002;  47 720-727
• 7 Thamer C, Haap M, Volk A, Maerker E, Becker R, Bachmann O, Machicao F, Häring H U, Stumvoll M. Evidence for greater oxidative substrate flexibility in male carriers of the Pro 12 Ala polymorphism in PPARgamma2.  Horm Metab Res. 2002;  34 132-136
• 8 Bachmann O P, Dahl D B, Brechtel K, Machann J, Haap M, Maier T, Loviscach M, Stumvoll M, Claussen C D, Schick F, Häring H U, Jacob S. Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans.  Diabetes. 2001;  50 2579-2584
• 9 Schick F, Eismann B, Jung W I, Bongers H, Bunse M, Lutz O. Comparison of localized proton NMR signals of skeletal muscle and fat tissue in vivo: two lipid compartments in muscle tissue.  Magn Reson Med. 1993;  29 158-167
• 10 Boesch C, Kreis R. MR-spectroscopy (MRS) of different nuclei applied to human muscle: additional information obtained by 1H-MRS.  Int J Sports Med. 1997;  18 (Suppl. 4) S310-S312
• 11 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
• 12 Polgar J, Johnson M A, Weightman D, Appleton D. Data on fibre size in thirty-six human muscles. An autopsy study.  J Neurol Sci. 1973;  19 307-318