Skip to main content

Biotin deficiency in mice is associated with decreased serum availability of insulin-like growth factor-I

Abstract

Background

Biotin deficiency leads to decreased weight and nose-rump length in mice.

Aim of the study

The mechanisms underlying this impairment in body growth are yet unclear. Biotin restriction, however, could affect the availability of growth hormone (GH) and/or insulin like growth factor-I (IGF-I) since both hormones control body growth. We then conducted a correlative study aimed at establishing whether biotin dietary restriction is associated with decreased GH/IGF-I serum concentrations.

Methods

Levels of GH and IGF-I were measured through ELISA in serum samples of male BALB/cAnN mice fed with: 1] standard chow diet (control diet); 2] 30% egg-white biotin-deficient diet; or 3] 30% egg-white diet supplemented with 16.4 µmol biotin per kilogram (biotin sufficient diet). Relative food consumption, as adjusted per gram of body weight, was also determined. GH and IGF-I measurements were taken individually for 20 weeks beginning at the postnatal week 3, when the animals started consuming the corresponding diets. In addition, femur’s weight and longitudinal growth and the organization of its growth plate were all analyzed as indicators of GH/IGF-I function.

Results

No differences in relative food consumption were observed among the three groups of mice along the experimental period that was evaluated. IGF-I serum levels, but not GH ones, were decreased in biotin deficient mice. These animals also showed decreased femur’s longitudinal growth, speed of lengthening and weight gain, as well as shorter and disorganized growth plates.

Conclusions

This study shows that biotin dietary restriction is indeed associated with decreased availability of IGF-I and diminished long bone growth and elongation. These conditions could explain the impairment of longitudinal body growth previously reported in biotin deficient mice. Although cause-effect studies are still needed, we believe our results support the notion that biotin might modulate the availability of IGF-I.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

Abbreviations

BD:

Biotin deficient

BS:

Biotin sufficient

GH:

Somatotropin or growth hormone

IGF-I:

Insulin-like growth factor I

References

  1. Báez-Saldaña A, Ortega E (2004) Biotin deficiency blocks thymocyte maturation, accelerates thymus involution, and decreases nose-rump length in mice. J Nutr 179:1970–1977

    Google Scholar 

  2. Báez-Saldaña A, Diaz G, Espinoza B, Ortega E (1998) Biotin deficiency induces changes in subpopulations of spleen lymphocytes in mice. Am J Clin Nutr 67:431–437

    Google Scholar 

  3. Bain SD, Newbrey JW, Watkins BA (1988) Biotin deficiency may alter tibiotarsal bone growth and modeling in broiler chicks. Poult Sci 67:590–595

    CAS  Google Scholar 

  4. Baker J, Liu JP, Robertson EJ, Efstratiadis A (1993) Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75:73–82

    CAS  Google Scholar 

  5. Balnave D (1997) Clinical symptoms of biotin deficiency in animals. Am J Clin Nutr 30:1408–1413

    Google Scholar 

  6. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  7. Breur GJ, VanEnkevort BA, Farnum CE, Wilsman NJ (1991) Linear relationship between the volume of hypertrophic chondrocytes and the rate of longitudinal bone growth in growth plates. J Orth Res 9:348–359

    Article  CAS  Google Scholar 

  8. Clark RG, Mortensen DL, Carlsson LM, Spencer SA, McKay P, Mulkerrin M, Moore J, Cunningham BC (1996) Recombinant human growth hormone (GH)-binding protein enhances the growth-promoting activity of human GH in the rat. Endocrinology 137:4308–4315

    Article  CAS  Google Scholar 

  9. Dakshinamurti K, Chauhan J (1998) Biotin. Vitam Horm 45:337–384

    Article  Google Scholar 

  10. Efstratiadis A (1998) Genetics of mouse growth. Int J Dev Biol 42:955–976

    CAS  Google Scholar 

  11. Fielder PJ, Mortensen DL, Mallet P, Carlsson B, Baxter RC, Clark RG (1996) Differential long-term effects of insulin-like growth factor-I (IGF-I) growth hormone (GH), and IGF-I plus GH on body growth and IGF binding proteins in hypophysectomized rats. Endocrinology 137:1913–1920

    Article  CAS  Google Scholar 

  12. Fliesen T, Maiter D, Gerard G, Underwood LE, Maes M, Ketelsleger J-M (1989) Reduction of serum insulin-like growth factor-I by dietary protein restriction is age dependent. Pediatr Res 26:415–419

    Article  CAS  Google Scholar 

  13. Friedrich W (1988) Vitamins. Walter de Gruyter, Berlin

    Google Scholar 

  14. Fryburg DA (1994) Insulin-like growth factor I exerts growth hormone and insulin-like actions on human muscle protein metabolism. Am J Physiol 267:E331–E336

    CAS  Google Scholar 

  15. Fryburg DA, Jahn LA, Hill SA, Oliveras DM, Barrett EJ (1995) Insulin and insulin-like growth factor I enhance human skeletal muscle protein anabolism during hyperaminoacidemia by different mechanisms. J Clin Invest 96:1722–1729

    Article  CAS  Google Scholar 

  16. Furukawa Y, Numazawa T, Fukazawa H, Ikai M, Ohinata K, Maebashi M, Kim DH, Ito M, Komai M, Kimura S (1993) Biochemical consequences of biotin deficiency in osteogenic disorder shionogi rats. Int J Vitam Nutr Res 63:129–134

    CAS  Google Scholar 

  17. Garciadiego-Cázares D, Rosales C, Katoh M, Chimal-Monroy J (2004) Coordination of chondrocyte differentiation and joint formation by α5β1 integrin in the developing appendicular skeleton. Development 131:4735–4742

    Article  CAS  Google Scholar 

  18. Harada N, Oda Z, Hara Y, Fujinami K, Okawa M, Ohbuchi K, Yonemoto M, Ikeda Y, Ohkawi K, Aragane K, Tamai Y, Kisunoki J (2007) Hepatic de novo lipogenesis is present in liver specific ACC-1 deficient mice. Mol Cell Biol 27:1881–1888

    Article  CAS  Google Scholar 

  19. Harel Z, Tannebaum GS (1993) Dietary protein restriction impairs both spontaneous and growth hormone-releasing factor-stimulated growth hormone release in the rat. Endocrinology 133:1035–1043

    Article  CAS  Google Scholar 

  20. Hunziker EB, Schenk RK (1989) Physiological mechanisms adopted by chondrocytes in regulating longitudinal bone growth in rats. J Physiol (Lond) 414:55–71

    CAS  Google Scholar 

  21. Hunziker EB, Wagner J, Zapf J (1994) Differential effects of insulin-like growth factor I and growth hormone on developmental stages of rat growth plate chondrocytes in vivo. J Clin Inv 93:1078–1086

    Article  CAS  Google Scholar 

  22. Jones JI, Clemmons DR (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16:3–34

    CAS  Google Scholar 

  23. Kostyo JL (1968) Rapid effects of growth hormone on aminoacid transport and protein synthesis. Ann NY Acad Sci 148:389–407

    Article  CAS  Google Scholar 

  24. Kothapalli N, Camporeale G, Kueh A, Chew YC, Oommen AM, Griffin JB, Zempleni J (2005) Biological functions of biotinylated histones. J Nutr Biochem 16:446–448

    Article  CAS  Google Scholar 

  25. LeRoith D, Bondy C, Yakar S, Liu J, Butler A (2001) The somatomedin hypothesis. Endocr Rev 22:53–74

    Article  CAS  Google Scholar 

  26. Lupu F, Terwilliger JD, Lee K, Segre GV, Efstratiadis A (2001) Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev Biol 229:141–162

    Article  CAS  Google Scholar 

  27. MacLeod JN, Pampori NA, Shapiro BH (1991) Sex differences in the ultradian pattern of plasma growth hormone concentrations in mice. J Endocrinol 131:395–399

    Article  CAS  Google Scholar 

  28. Mejia WN, Yakar S, Sanchez-Gomez M, Umana PA, Setser J, LeRoith D (2002) Protein calorie restriction affects nonhepatic IGF-I production and the lymphoid system: studies using the liver-specific IGF-I gene-deleted mouse model. Endocrinology 143:2233–2241

    Article  Google Scholar 

  29. Mejia-Naranjo W, Yakar S, Bernal R, LeRoith D, Sanchez-Gomez M (2003) Regulation of the splenic somatotropic axis by dietary protein and insulin-like growth factor-I in the rat. Growth Horm IGF Res 13:254–263

    Article  CAS  Google Scholar 

  30. Mock DM (1990) Evidence for a pathogenic role of w6 polyunsaturated fatty acids in the cutaneous manifestations of biotin deficiency. J Ped Gastro Nutr 10:222–229

    CAS  Article  Google Scholar 

  31. Montgomery R, Dryer RL, Conway TW, Spector AA (1980) Biochemistry: a case-oriented approach. The CV Mosby Company, St. Louis

    Google Scholar 

  32. Nijhout HF (2003) The control of growth. Development 130:5683–5687

    Article  CAS  Google Scholar 

  33. Ohlsson C, Nilsson A, Isaksson OGP, Lindahl A (1992) Growth hormone induces multiplication of the slowly cycling germinal cells of the rat tibial growth plate. Proc Natl Acad Sci USA 89:9826–9830

    Article  CAS  Google Scholar 

  34. Ohlsson C, Bengtsson B-A, Isaksson OGP, Andreassen TT, Slootweg MC (1998) Growth hormone and bone. Endocr Rev 19:55–79

    Article  CAS  Google Scholar 

  35. Patel MS, Mistry SP (1968) Effect of biotin deficiency on food intake and body and organ weights of male albino rats. Growth 32:175–187

    CAS  Google Scholar 

  36. Pattie WA, Williams AJ (1967) Selection for weaning weight in Merino sheep: 3. Maintenance requirements and the efficiency of conversion of feed to wool in mature ewes. Aust J Exp Agric Anim Husb 7(25):117–125

    Article  Google Scholar 

  37. Renaville R, Hammadi M, Potetelle D (2003) Role of the somatotropic axis in the mammalian metabolism. Domest Anim Endocrinol 23:351–360

    Article  Google Scholar 

  38. Rodriguez-Melendez R, Zempleni J (2003) Regulation of gene expression by biotin (review). J Nutr Biochem 14:680–690

    Article  CAS  Google Scholar 

  39. Romero-Navarro G, Cabrera-Valladares G, German MS, Matschinsky FM, Velazquez A, Wang J, Fernandez-Mejia C (1999) Biotin regulation of pancreatic glucokinase and insulin in primary cultured rat islets and in biotin-deficient rats. Endocrinology 140:4595–4600

    Article  CAS  Google Scholar 

  40. Schrijver J, Dias T, Hommes FA (1979) Some biochemical observations on biotin deficiency in the rat as a model for human Pyruvate carboxylase deficiency. Nutr Metab 23:179–191

    Article  CAS  Google Scholar 

  41. Stewart CEH, Rotwein P (1996) Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. Physiol Rev 76:1005–1026

    CAS  Google Scholar 

  42. Thissen JP, Ketelslegers JM, Underwood LE (1994) Nutritional regulation of the insulin-like growth factors. Endocr Rev 15:80–101

    CAS  Google Scholar 

  43. Wallenius K, Sjögren K, Peng X-D, Park S, Wallenius V, Liu J-L, Umaerus M, Wennbo H, Isaksson O, Frohman L, Kineman R, Ohlson C, Jansson J-O (2001) Liver-derived IGF-I regulates GH secretion at the pituitary level in mice. Endocrinology 142:4762–4770

    Article  CAS  Google Scholar 

  44. Wang J, Zhou J, Cheng CM, Kopchick JJ, Bondy CA (2004) Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth. J Endocrinol 180:247–255

    Article  CAS  Google Scholar 

  45. Yakar S, Rossen CJ, Beamer WG, Ackert-Bicknell ChL, Wu Y, Liu J-L, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D (2002) Circulating levels of IGF-I directly regulate bone growth and density. J Clin Invest 110:771–781

    CAS  Google Scholar 

  46. Zeigler HP, Green HL, Siegel J (1972) Food and water intake and weight regulation in the pigeon. Physiol Behav 8:127–134

    Article  CAS  Google Scholar 

  47. Zempleni J (2005) Uptake, localization, and noncarboxylase roles of biotin. Annu Rev Nutr 25:175–196

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank to Georgina Díaz for providing animal care assistance, to David Garciadiego-Cázares for the histological processing, and to Georgina Del Vecchyo for her encouragement in achieving femur measurements. Authors are also grateful to Dr. David Riddle for helpful criticisms and editing.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Armida Báez-Saldaña PhD.

Additional information

This work was supported by grants from the Dirección General de Asuntos del Personal Académico (DGAPA), Universidad Nacional Autónoma de México (PAPIIT IN230905, IN200205, IN208605) and the Consejo Nacional de Ciencia y Tecnología, México (52746, 42568Q).

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Báez-Saldaña, A., Gutiérrez-Ospina, G., Chimal-Monroy, J. et al. Biotin deficiency in mice is associated with decreased serum availability of insulin-like growth factor-I. Eur J Nutr 48, 137–144 (2009). https://doi.org/10.1007/s00394-009-0773-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-009-0773-8

Keywords

  • body growth
  • body size
  • bone growth
  • nutrition
  • vitamins
  • growth hormone