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Short-term exposure to low-carbohydrate, high-fat diets induces low bone mineral density and reduces bone formation in rats

  1. Maximilian Bielohuby1,
  2. Maiko Matsuura2,
  3. Nadja Herbach3,
  4. Ellen Kienzle4,
  5. Marc Slawik1,
  6. Andreas Hoeflich5,
  7. Martin Bidlingmaier1,*

Article first published online: 14 DEC 2009

DOI: 10.1359/jbmr.090813

Issue

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Volume 25, Issue 2, pages 275–284, February 2010

Additional Information

How to Cite

Bielohuby, M., Matsuura, M., Herbach, N., Kienzle, E., Slawik, M., Hoeflich, A. and Bidlingmaier, M. (2010), Short-term exposure to low-carbohydrate, high-fat diets induces low bone mineral density and reduces bone formation in rats. Journal of Bone and Mineral Research, 25: 275–284. doi: 10.1359/jbmr.090813

Author Information

  1. 1

    Endocrine Research Unit, Medizinische Klinik - Innenstadt, Ludwig Maximilians University, Munich, Germany

  2. 2

    Institute of Anatomy, Ludwig Maximilians University, Munich, Germany

  3. 3

    Institute of Veterinary Pathology, Ludwig Maximilians University, Munich, Germany

  4. 4

    Chair of Animal Nutrition and Dietetics, Ludwig Maximilians University, Munich, Germany

  5. 5

    Laboratory of Mouse Genetics, Research Unit Genetics and Biometry, Research Institute for the Biology of Farm Animals - FBN Dummerstorf, Germany

*Medizinische Klinik - Innenstadt, Klinikum der Universität, Ziemssenstr. 1, 80336 Munich, Germany.

Publication History

  1. Issue published online: 19 FEB 2010
  2. Article first published online: 14 DEC 2009
  3. Manuscript Accepted: 13 JUL 2009
  4. Manuscript Revised: 16 JUN 2009
  5. Manuscript Received: 7 APR 2009

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References

  • 1
    Shai I, Schwarzfuchs D, Henkin Y, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med 2008; 359: 229–241.
  • 2
    Reddy ST, Wang CY, Sakhaee K, Brinkley L, Pak CY. Effect of low-carbohydrate, high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism. Am J Kidney Dis 2002; 40: 265–274.
  • 3
    Carter JD, Vasey FB, Valeriano J. The effect of a low-carbohydrate diet on bone turnover. Osteoporos Int 2006; 17: 1398–1403.
  • 4
    Porta N, Vallee L, Boutry E, et al. Comparison of seizure reduction and serum fatty acid levels after receiving the ketogenic and modified Atkins diet. Seizure 2009; 18: 359–364.
  • 5
    Neal EG, Chaffe HM, Edwards N, Lawson MS, Schwartz RH, Cross JH. Growth of children on classical and medium-chain triglyceride ketogenic diets. Pediatrics 2008; 122: e334–e340.
  • 6
    Bergqvist AG, Schall JI, Stallings VA, Zemel BS. Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. Am J Clin Nutr 2008; 88: 1678–1684.
  • 7
    Zernicke RF, Salem GJ, Barnard RJ, Schramm E. Long-term, high-fat-sucrose diet alters rat femoral neck and vertebral morphology, bone mineral content, and mechanical properties. Bone 1995; 16: 25–31.
  • 8
    Lac G, Cavalie H, Ebal E, Michaux O. Effects of a high fat diet on bone of growing rats: correlations between visceral fat, adiponectin and bone mass density. Lipids Health Dis 2008; 7: 16.
  • 9
    Mardon J, Habauzit V, Trzeciakiewicz A, et al. Influence of high and low protein intakes on age-related bone loss in rats submitted to adequate or restricted energy conditions. Calcif Tissue Int 2008; 82: 373–382.
  • 10
    Hamrick MW, Ding KH, Ponnala S, Ferrari SL, Isales CM. Caloric restriction decreases cortical bone mass but spares trabecular bone in the mouse skeleton: implications for the regulation of bone mass by body weight. J Bone Miner Res 2008; 23: 870–878.
  • 11
    Caton SJ, Yinglong B, Burget L, Spangler LJ, Tschop MH, Bidlingmaier M. Low-carbohydrate high-fat diets: Regulation of energy balance and body weight regain in rats. Obesity (Silver Spring) 2009; 17: 283–289.
  • 12
    Malluche HH, Koszewski N, Monier-Faugere MC, Williams JP, Mawad H. Influence of the parathyroid glands on bone metabolism. Eur J Clin Invest 2006; 36: S23–S33.
  • 13
    Riggs BL, Khosla S, Melton LJ III. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002; 23: 279–302.
  • 14
    Laviola L, Natalicchio A, Perrini S, Giorgino F. Abnormalities of IGF-I signaling in the pathogenesis of diseases of the bone, brain, and fetoplacental unit in humans. Am J Physiol Endocrinol Metab 2008; 295: E991–E999.
  • 15
    Wang Y, Nishida S, Sakata T, et al. Insulin-like growth factor I is essential for embryonic bone development. Endocrinology 2006; 147: 4753–4761.
  • 16
    Boudignon BM, Bikle DD, Kurimoto P, et al. Insulin-like growth factor I stimulates recovery of bone lost after a period of skeletal unloading. J Appl Physiol 2007; 103: 125–131.
  • 17
    Tanaka H, Quarto R, Williams S, Barnes J, Liang CT. In vivo and in vitro effects of insulin-like growth factor I (IGF-I) on femoral mRNA expression in old rats. Bone 1994; 15: 647–653.
  • 18
    Isgaard J, Nilsson A, Lindahl A, Jansson JO, Isaksson OG. Effects of local administration of GH and IGF-1 on longitudinal bone growth in rats. Am J Physiol 1986; 250: E367–E372.
  • 19
    Isaksson OG, Lindahl A, Nilsson A, Isgaard J. Mechanism of the stimulatory effect of growth hormone on longitudinal bone growth. Endocr Rev 1987; 8: 426–438.
  • 20
    Ohlsson C, Bengtsson BA, Isaksson OG, Andreassen TT, Slootweg MC. Growth hormone and bone. Endocr Rev 1998; 19: 55–79.
  • 21
    Eckstein F, Pavicic T, Nedbal S, et al. Insulin-like growth factor binding protein 2 (IGFBP-2) overexpression negatively regulates bone size and mass, but not density, in the absence and presence of growth hormone/IGF-I excess in transgenic mice. Anat Embryol (Berl) 2002; 206: 139–148.
  • 22
    Hoeflich A, Gotz W, Lichanska AM, Bielohuby M, Tonshoff B, Kiepe D. Effects of insulin-like growth factor binding proteins in bone: a matter of cell and site. Arch Physiol Biochem 2007; 113: 142–153.
  • 23
    Lee NK, Karsenty G. Reciprocal regulation of bone and energy metabolism. Trends Endocrinol Metab 2008; 19: 161–166.
  • 24
    Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143–147.
  • 25
    Ziros PG, Basdra EK, Papavassiliou AG. Runx2: of bone and stretch. Int J Biochem Cell Biol 2008; 40: 1659–1663.
  • 26
    Tominaga H, Maeda S, Hayashi M, et al. CCAAT/enhancer-binding protein beta promotes osteoblast differentiation by enhancing Runx2 activity with ATF4. Mol Biol Cell 2008; 19: 5373–5386.
  • 27
    National. Research Council. Nutritional Requiremnets of Laboratory Animals. 4th ed. Washington: National Academy of Sciences; 1995.
  • 28
    Hoeflich A, Weber MM, Fisch T, et al. Insulin-like growth factor binding protein 2 (IGFBP-2) separates hypertrophic and hyperplastic effects of growth hormone (GH)/IGF-I excess on adrenocortical cells in vivo. FASEB J 2002; 16: 1721–1731.
  • 29
    Hunt JR, Hunt CD, Zito CA, Idso JP, Johnson LK. Calcium requirements of growing rats based on bone mass, structure, or biomechanical strength are similar. J Nutr 2008; 138: 1462–1468.
  • 30
    Williams EA, Perkins SN, Smith NC, Hursting SD, Lane MA. Carbohydrate versus energy restriction: effects on weight loss, body composition and metabolism. Ann Nutr Metab 2007; 51: 232–243.
  • 31
    Ward WE, Kim S, Robert Bruce W. A western-style diet reduces bone mass and biomechanical bone strength to a greater extent in male compared with female rats during development. Br J Nutr 2003; 90: 589–595.
  • 32
    Salem GJ, Zernicke RF, Barnard RJ. Diet-related changes in mechanical properties of rat vertebrae. Am J Physiol 1992; 262: R318–R321.
  • 33
    Smith EE, Ferguson VL, Simske SJ, Gayles EC, Pagliassotti MJ. Effects of high fat or high sucrose diets on rat femora mechanical and compositional properties. Biomed Sci Instrum 2000; 36: 385–390.
  • 34
    Karsenty G. Convergence between bone and energy homeostases: leptin regulation of bone mass. Cell Metab 2006; 4: 341–348.
  • 35
    Thomas T. The complex effects of leptin on bone metabolism through multiple pathways. Curr Opin Pharmacol 2004; 4: 295–300.
  • 36
    Hamrick MW, Della-Fera MA, Choi YH, Pennington C, Hartzell D, Baile CA. Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. J Bone Miner Res 2005; 20: 994–1001.
  • 37
    Stevenson AE, Evans BA, Gevers EF, et al. Does adiposity status influence femoral cortical strength in rodent models of growth hormone deficiency? Am J Physiol Endocrinol Metab 2009; 296: E147–E156.
  • 38
    Elefteriou F, Takeda S, Ebihara K, et al. Serum leptin level is a regulator of bone mass. Proc Natl Acad Sci USA 2004; 101: 3258–3263.
  • 39
    Takeda S, Elefteriou F, Levasseur R, et al. Leptin regulates bone formation via the sympathetic nervous system. Cell 2002; 111: 305–317.
  • 40
    Martin A, David V, Malaval L, Lafage-Proust MH, Vico L, Thomas T. Opposite effects of leptin on bone metabolism: a dose-dependent balance related to energy intake and insulin-like growth factor I pathway. Endocrinology 2007; 148: 3419–3425.
  • 41
    Li R, Svenson KL, Donahue LR, Peters LL, Churchill GA. Relationships of dietary fat, body composition, and bone mineral density in inbred mouse strain panels. Physiol Genom 2008; 33: 26–32.
  • 42
    Meunier P, Aaron J, Edouard C, Vignon G. Osteoporosis and the replacement of cell populations of the marrow by adipose tissue: a quantitative study of 84 iliac bone biopsies. Clin Orthop Relat Res 1971; 80: 147–154.
  • 43
    Burkhardt R, Kettner G, Bohm W, et al. Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age: a comparative histomorphometric study. Bone 1987; 8: 157–164.
  • 44
    Nuttall ME, Gimble JM. Is there a therapeutic opportunity to either prevent or treat osteopenic disorders by inhibiting marrow adipogenesis? Bone 2000; 27: 177–184.
  • 45
    Scariano JK, Glew RH, Bou-Serhal CE, Clemens JD, Garry PJ, Baumgartner RN. Serum levels of cross-linked N-telopeptides and aminoterminal propeptides of type I collagen indicate low bone mineral density in elderly women. Bone 1998; 23: 471–477.
  • 46
    Ziros PG, Georgakopoulos T, Habeos I, Basdra EK, Papavassiliou AG. Growth hormone attenuates the transcriptional activity of Runx2 by facilitating its physical association with Stat3β. J Bone Miner Res 2004; 19: 1892–1904 .
  • 47
    Celil AB, Campbell PG. BMP-2 and insulin-like growth factor I mediate Osterix (Osx) expression in human mesenchymal stem cells via the MAPK and protein kinase D signaling pathways. J Biol Chem 2005; 280: 31353–31359.
  • 48
    Ito S, Suzuki N, Kato S, Takahashi T, Takagi M. Glucocorticoids induce the differentiation of a mesenchymal progenitor cell line, ROB-C26 into adipocytes and osteoblasts, but fail to induce terminal osteoblast differentiation. Bone 2007; 40: 84–92.
  • 49
    Kanemaru K, Seya K, Miki I, Motomura S, Furukawa K. Calcification of aortic smooth muscle cells isolated from spontaneously hypertensive rats. J Pharmacol Sci 2008; 106: 280–286.
  • 50
    Chen J, Kunos G, Gao B. Ethanol rapidly inhibits IL-6-activated STAT3 and C/EBP mRNA expression in freshly isolated rat hepatocytes. FEBS Lett 1999; 457: 162–168.
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