Study on the Distribution and Elimination of the New Hormone Irisin In Vivo: New Discoveries Regarding Irisin

Abstract

Irisin is a newly discovered factor that is secreted by skeletal muscle and plays an important role in the homeostasis and metabolism of energy balance. This study used irisin radiolabeled with ¹²⁵I and small-animal SPECT/CT imaging to investigate the metabolic elimination and distribution of irisin in vivo. Irisin was labeled with ¹²⁵I using the Iodogen method. Small-animal SPECT/CT imaging was performed on C57/B16 mice at 15, 30, 60, 120, and 240 min after receiving a tail vein injection, and the radioactive distribution in the organs of mice was determined at 15, 60, and 120 min. Small-animal SPECT/CT imaging revealed the highest level of radioactivity in the gallbladder followed by the liver and kidney. Radioactivity decreased gradually with time in all organs. The radioactive distribution in the mice organs also showed that the highest %ID/g was in the gallbladder followed by the kidney and liver, and decreased gradually with time. The radioactivity in the gastric system reached its highest level at 60 min. Finally, our study showed the metabolic clearance of ¹²⁵I-irisin is achieved primarily through the hepatobiliary and renal system and provided the basis for the clinical application of irisin.

Key words

iodine-125 radionuclide - small-animal SPECT/CT - hepatobiliary clearance - renal clearance

^*  These authors contributed equally to this work.

• References

• 1 Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA 2013; 309: 71-82
• 2 Novelle MG, Contreras C, Romero-Pico A, Lopez M, Dieguez C. Irisin, two years later. Int J Endocrinol 2013; 2013: 1-8
• 3 Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Hojlund K, Gygi SP, Spiegelman BM. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481: 463-468
• 4 Castillo-Quan JI. From white to brown fat through the PGC-1alpha-dependent myokine irisin: implications for diabetes and obesity. Dis Model Mech 2012; 5: 293-295
• 5 Charos AE, Reed BD, Raha D, Szekely AM, Weissman SM, Snyder M. A highly integrated and complex PPARGC1A transcription factor binding network in HepG2 cells. Genome Res 2012; 22: 1668-1679
• 6 Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, Huang K, Tu H, van Marken Lichtenbelt WD, Hoeks J, Enerback S, Schrauwen P, Spiegelman BM. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012; 150: 366-376
• 7 Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D, Penicaud L, Casteilla L. Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci 1992; 103: 931-942
• 8 Cunha A. Basic research: Irisin – behind the benefits of exercise. Nat Rev Endocrinol 2012; 8: 195
• 9 Diao L, Meibohm B. Pharmacokinetics and pharmacokinetic-pharmacodynamic correlations of therapeutic peptides. Clin Pharmacokinet 2013; 52: 855-868
• 10 Carone FA, Peterson DR. Hydrolysis and transport of small peptides by the proximal tubule. Am J Physiol 1980; 238: 151-158
• 11 Tolmachev V, Orlova A, Lundqvist H. Approaches to improve cellular retention of radiohalogen labels delivered by internalising tumour-targeting proteins and peptides. Curr Med Chem 2003; 10: 2447-2460
• 12 Zhang HJ, Zhang XF, Ma ZM, Pan LL, Chen Z, Han HW, Han CK, Zhuang XJ, Lu Y, Li XJ, Yang SY, Li XY. Irisin is inversely associated with intrahepatic triglyceride contents in obese adults. J Hepatol 2013; 59: 557-562