Article :: Shortterm exposure to lowcarbohydrate highfat diets induces low bone mineral density and reduces bone formation in rats

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Original Article

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

Maximilian Bielohuby¹, Maiko Matsuura², Nadja Herbach³, Ellen Kienzle⁴, Marc Slawik¹, Andreas Hoeflich⁵, Martin Bidlingmaier^{1 *}

¹Endocrine Research Unit, Medizinische Klinik - Innenstadt, Ludwig Maximilians University, Munich, Germany
²Institute of Anatomy, Ludwig Maximilians University, Munich, Germany
³Institute of Veterinary Pathology, Ludwig Maximilians University, Munich, Germany
⁴Chair of Animal Nutrition and Dietetics, Ludwig Maximilians University, Munich, Germany
⁵Laboratory of Mouse Genetics, Research Unit Genetics and Biometry, Research Institute for the Biology of Farm Animals - FBN Dummerstorf, Germany

email: Martin Bidlingmaier (martin.bidlingmaier@med.uni-muenchen.de)

^*Correspondence to Martin Bidlingmaier, Medizinische Klinik - Innenstadt, Klinikum der Universität, Ziemssenstr. 1, 80336 Munich, Germany.

Keywords

Atkins-style diets bone growth GH/IGF system obesity differentiation of mesenchymal cells in bone marrow

Abstract

Low-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in adults and are also used as part of a treatment for children with epilepsy. However, potential risks and side effects remain controversial. We investigated effects of LC-HF diets on growth, bone mineral density (BMD), and turnover in growing rats fed for 4 weeks either normal chow (CH, 9% fat, 33% protein, and 58% carbohydrates), LC-HF-1 (66% fat, 33% protein, and 1% carbohydrates), or LC-HF-2 (94.5% fat, 4.2% protein, and 1.3% carbohydrates). Rats fed LC-HF diets accumulated significantly more visceral and bone marrow fat and showed increased leptin but decreased insulin-like growth-factor 1 (IGF-1). Both LC-HF diets significantly decreased body length (nose to rump), but lengths of humerus, tibia, and femur were significantly reduced with LC-HF-2 only. Peripheral quantitative computed tomography (pQCT) and micro-CT (µCT) independently revealed significant reductions in BMD of tibiae in both LC-HF groups, and tibial maximum load was impaired. Bone-formation marker N-terminal propeptide of type I procollagen was reduced in sera of LC-HF groups, whereas bone resorption marker CrossLaps remained unchanged. Real-time PCR analysis revealed significant reductions by 70% to 80% of transcription factors influencing osteoblastogenesis (Runx2, osterix, and C/EBP) in bone marrow of rats fed LC-HF diets. In conclusion, both LC-HF diets impaired longitudinal growth, BMD, and mechanical properties, possibly mediated by reductions in circulating IGF-1. Serum bone-formation markers as well as expression of transcription factors influencing osteoblastogenesis were reduced. This might indicate a lower rate of mesenchymal stem cells differentiating into osteoblasts, thus explaining reduced bone formation with LC-HF diets. © 2010 American Society for Bone and Mineral Research