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The Effects of Calcium Channel Blocker Benidipine and Calmodulin Antagonist W7 on GDP-Binding Capacity of Brown Adipose Tissue in Mice

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Abstract

It has been suggested that increased dietary calcium intake can attenuate obesity. Calcium antagonists, such as benidipine, also have been shown to have an anti-obesity effect. However, the mechanism for calcium-related anti-obesity effect has not yet been established. A defective brown adipose tissue thermogenesis has been shown in obese rodents. This study was designed to examine the direct effects of calcium channel blocker benidipine and calmodulin antagonist W7 administration on the adaptive thermogenesis in brown adipose tissue taken from the genetically obese mice and their lean controls. The GDP binding to brown-fat cell mitochondria was used as a brown adipose tissue thermogenic index. The results show that benidipine treatment had no marked effect on brown-fat cell GDP-binding capacities in both obese and lean mice. However, GDP-binding capacities were significantly reduced in both obese and lean mice after the W7 administration. The results of this study support the previous finding that benidipine did not have direct thermogenic effect on brown adipose tissue and suggest that the change in intracellular calmodulin availability might contribute to the adaptive thermogenesis in brown adipose tissue.

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References

  1. Kopelman PG (2000) Obesity as a medical problem. Nature 404:635–643

    PubMed  CAS  Google Scholar 

  2. Bray GA (1999) Etiology and pathogenesis of obesity. Clin Cornerstone 2:1–15

    Article  PubMed  CAS  Google Scholar 

  3. Zemel MB (2002) Regulation of adiposity and obesity risk by dietary calcium: mechanism and implications. J Am Coll Nutr 21:146S–151S

    PubMed  CAS  Google Scholar 

  4. Pereira M, Jacobs DR, Van Horn L, Slattery ML, Kartashov AI, Ludwig DS (2002) Dairy consumption, obesity, and the insulin resistance syndrome in young adults: the CARDIA Study. J Am Med Assoc 287:2081–2089

    Article  Google Scholar 

  5. Levy J, Gavin JR, Sowers JR (1994) Diabetes mellitus: a disease of abnormal cellular-calcium metabolism. Am J Med 96:260–273

    Article  PubMed  CAS  Google Scholar 

  6. Resnick LH (1992) Cellular ions in hypertension, insulin resistance, obesity, and diabetes: a unifying theme. J Am Soc Nephrol 3(suppl.l):s78–s85

    PubMed  CAS  Google Scholar 

  7. DeFronzo RA, Ferrannini E (1991) Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14:173–194

    Article  PubMed  CAS  Google Scholar 

  8. Nedergaard J (1983) The relationship between extramitochondrial Ca2+ concentration, respiratory rate, and membrane potential in mitochondria from brown adipose tissue of the rat. Eur J Biochem 133:185–191

    Article  PubMed  CAS  Google Scholar 

  9. Shi H, Halvorsen Y, Ellis PN, Wilkison WO, Zemel MB (2000) Role of intracellular calcium in human adipocyte differentiation. Physiol Genomics 3:75–82

    PubMed  CAS  Google Scholar 

  10. Zemel MB, Shi H, Greer B, Dirienzo D, Zemel PC (2000) Regulation of adiposity by dietary calcium. FASEB J 14:1132–1138

    PubMed  CAS  Google Scholar 

  11. De-Meis L (2003) Brown adipose tissue Ca2+-ATPase: uncoupled ATP hydrolysis and thermogenic activity. J Biol Chem 278:41856–41861

    Article  PubMed  CAS  Google Scholar 

  12. Mirmiran P, Esmaillzadeh A, Azizi F (2005) Dairy consumption and body mass index: an inverse relationship. Int J Obes 29:115–121

    Article  CAS  Google Scholar 

  13. Schrager S (2005) Dietary calcium intake and obesity. J Am Board Fam Pract 18:205–210

    Article  PubMed  Google Scholar 

  14. Zemel MB, Richards J, Mathis S, Milstead A, Gebhardt L, Silva E (2005) Dairy augmentation of total and central fat loss in obese subjects. Int J Obes 29:391–397

    Article  CAS  Google Scholar 

  15. Huang TTK, McCrory MA (2005) Dairy intake, obesity, and metabolic health in children and adolescents: knowledge and gaps. Nutr Rev 63:71–80

    Article  PubMed  Google Scholar 

  16. Harris RBS (2005) Dairy protein, calcium and body weight—the need for a mechanism. Int J Obes 29:388–390

    Article  CAS  Google Scholar 

  17. Kim JH, Mynatt RL, Moore JW, Woychik RP, Moustaid N, Zemel MB (1996) The effects of calcium channel blockade on agouti-induced obesity. FASEB J 10:1646–1652

    PubMed  CAS  Google Scholar 

  18. Yoshida T, Umekawa T, Wakabayshi Y, Sakane N, Kondo M (1994) Mechanism of anti-obesity action of benidipine hydrochloride in mice. Int J Obesity 18:776–779

    CAS  Google Scholar 

  19. Sakane N, Kotani K, Hioki C, Yoshida T, Kawada T (2007) Up-regulation of muscle uncoupling protein 3 gene expression by calcium channel blocker, benidipine hydrochloride in rats. Endocrine J 54:771–775

    Article  CAS  Google Scholar 

  20. Zhao J, Golozoubova V, Bengtsson T, Cannon B, Nedergaard J (1999) Benidipine induces thermogenesis in brown adipose tissue by releasing endogenous noradrenaline: a possible mechanism for the anti-obesity effect of calcium antagonists. Int J Obes 23:238–245

    Article  CAS  Google Scholar 

  21. Cohen P, Blee CB (1988) Calmodulin. Elsevier, Amsterdam

    Google Scholar 

  22. Fournier L, Whitfield JF, Schwartz JL, Begin-Heick N (1994) Cyclic AMP triggers large [Ca2+]i oscillations in glucose-stimulated beta-cells from ob/ob mice. J Biol Chem 269:1120–1124

    PubMed  CAS  Google Scholar 

  23. Nadal A, Valdeolmillos M, Soria B (1994) Metabolic regulation of intracellular calcium concentration in mouse pancreatic islets of Langerhans. Am J Physiol 267:E769–E774

    PubMed  CAS  Google Scholar 

  24. Rehnmark S, Bianco AC, Kieffer JD, Silva JE (1992) Transcriptional and post-transcriptional mechanisms in uncoupling protein mRNA response to cold. Am J Physiol 262:E58–E67

    PubMed  CAS  Google Scholar 

  25. Rothwell NJ, Stock MJ (1988) Brown adipose tissue: does it play a role in the development of obesity? Diabetes Metab Rev 4:595–601

    Article  PubMed  CAS  Google Scholar 

  26. Lowell BB, Spiegelman BM (2000) Towards a molecular understanding of adaptive thermogenesis. Nature 404:652–660

    PubMed  CAS  Google Scholar 

  27. Fain JH, Reed N, Saperstein R (1967) The isolation and metabolism of brown fat cells. J Biol Chem 242:1887–1894

    PubMed  CAS  Google Scholar 

  28. Cannon B, Lindberg O (1979) Mitochondria from brown adipose tissue: isolation and properties. Methods Enzymol 55:65–78

    Article  PubMed  CAS  Google Scholar 

  29. Desutels M, Zaror-Behrens G, Himms-Hagen J (1978) Increased purine nucleotide binding, altered polypeptide composition, and thermogenesis in brown adipose tissue of cold-acclimated rats. Can J Biochem 56:378–383

    Article  Google Scholar 

  30. Chen MD, Lin PY, Chen PS, Cheng V, Lin WH (1997) Zinc attenuation of GDP binding to brown adipocytes mitochondria in genetically obese (ob/ob) mice. Biol Trace Elem Res 57:139–145

    Article  PubMed  CAS  Google Scholar 

  31. Harashima H, Kiwada H, Kajita J, Kobayashi S (1994) Effect of benidipine hydrochloride (Coniel), a new calcium antagonist, on the cardiac output, regional blood flow and vascular resistance in conscious, spontaneously hypertensive rats. Biopharm Durg Dispos 15:431–438

    Article  CAS  Google Scholar 

  32. Ackland ML, McArdle HJ (1996) Cation-dependent uptake of zinc in human fibroblasts. Biometals 9:29–37

    Article  PubMed  CAS  Google Scholar 

  33. Izawa T, Komabayashi T (1994) Ca2+ and lipolysis in adipocytes from exercise-trained rats. J Appl Physiol 77:2618–2624

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Science Council (NSC85-2311-B-029-001) and Overseas Chinese Institute of Technology (OCIT96A-063), Taiwan. We thank Drs. Wei-Chen Liao and Piin-Sheng Chen for their helpful discussion and technical assistance.

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, 407, Taiwan, Republic of China

    Yuh-Min Song

  2. Department of Chemistry, Tunghai University, Taichung, 407, Taiwan, Republic of China

    Pi-Yao Lin

  3. General Education Center, Overseas Chinese Institute of Technology, No. 100 Chiao-Kwang Road, Taichung, 407, Taiwan, Republic of China

    Ming-Der Chen

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  1. Yuh-Min Song
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  2. Pi-Yao Lin
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  3. Ming-Der Chen
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Correspondence to Ming-Der Chen.

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Song, YM., Lin, PY. & Chen, MD. The Effects of Calcium Channel Blocker Benidipine and Calmodulin Antagonist W7 on GDP-Binding Capacity of Brown Adipose Tissue in Mice. Biol Trace Elem Res 127, 245–250 (2009). https://doi.org/10.1007/s12011-008-8244-2

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  • DOI: https://doi.org/10.1007/s12011-008-8244-2

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