title: Short-term exposure to low-carbohydrate, high-fat diets induces low bone mineral density and reduces bone formation in rats.
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 (microCT) 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/EBPbeta) 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.
authors: Endocrine Research Unit, Medizinische Klinik - Innenstadt, Ludwig Maximilians University, Munich, Germany.
authors: Maximilian
authors: M
authors: Bielohuby
authors: Maiko
authors: M
authors: Matsuura
authors: Nadja
authors: N
authors: Herbach
authors: Ellen
authors: E
authors: Kienzle
authors: Marc
authors: M
authors: Slawik
authors: Andreas
authors: A
authors: Hoeflich
authors: Martin
authors: M
authors: Bidlingmaier
mesh_terms: D000818:Animals; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000648:ultrastructure; D002118:Calcium / Q000097:blood / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D002118:Calcium