title: Low-carbohydrate, high-fat diets have sex-specific effects on bone health in rats.
abstract: OBJECTIVE
  Studies in humans suggest that consumption of low-carbohydrate, high-fat diets (LC-HF) could be detrimental for growth and bone health. In young male rats, LC-HF diets negatively affect bone health by impairing the growth hormone/insulin-like growth factor axis (GH/IGF axis), while the effects in female rats remain unknown. Therefore, we investigated whether sex-specific effects of LC-HF diets on bone health exist.
  
  
  METHODS
  Twelve-week-old male and female Wistar rats were isoenergetically pair-fed either a control diet (CD), "Atkins-style" protein-matched diet (LC-HF-1), or ketogenic low-protein diet (LC-HF-2) for 4 weeks. In females, microcomputed tomography and histomorphometry analyses were performed on the distal femur. Sex hormones were analysed with liquid chromatography-tandem mass spectrometry, and endocrine parameters including GH and IGF-I were measured by immunoassay.
  
  
  RESULTS
  Trabecular bone volume, serum IGF-I and the bone formation marker P1NP were lower in male rats fed both LC-HF diets versus CD. LC-HF diets did not impair bone health in female rats, with no change in trabecular or cortical bone volume nor in serum markers of bone turnover between CD versus both LC-HF diet groups. Pituitary GH secretion was lower in female rats fed LC-HF diet, with no difference in circulating IGF-I. Circulating sex hormone concentrations remained unchanged in male and female rats fed LC-HF diets.
  
  
  CONCLUSIONS
  A 4-week consumption of LC-HF diets has sex-specific effects on bone health-with no effects in adult female rats yet negative effects in adult male rats. This response seems to be driven by a sex-specific effect of LC-HF diets on the GH/IGF system.
authors.affiliation: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstrasse 1, 80336, Munich, Germany.
authors.forename: Ayse
authors.initials: A
authors.lastname: Zengin
authors.affiliation: Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital of Munich (LMU), Campus Grosshadern, Marchioninistrasse 15, 81377, Munich, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Kropp
authors.affiliation: Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital of Munich (LMU), Campus Grosshadern, Marchioninistrasse 15, 81377, Munich, Germany.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chevalier
authors.affiliation: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstrasse 1, 80336, Munich, Germany.
authors.forename: Riia
authors.initials: R
authors.lastname: Junnila
authors.affiliation: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstrasse 1, 80336, Munich, Germany.
authors.forename: Elahu
authors.initials: E
authors.lastname: Sustarsic
authors.affiliation: Centre for Clinical Veterinary Medicine, Institute of Veterinary Pathology, LMU, Munich, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Herbach
authors.affiliation: Endocrinology Unit, Department of Medical and Surgical Sciences and Center for Applied Biomedical Research, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Flaminia
authors.initials: F
authors.lastname: Fanelli
authors.affiliation: Endocrinology Unit, Department of Medical and Surgical Sciences and Center for Applied Biomedical Research, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Mezzullo
authors.affiliation: Anatomische Anstalt, Lehrstuhl II, LMU, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Milz
authors.affiliation: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstrasse 1, 80336, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.affiliation: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstrasse 1, 80336, Munich, Germany. Maximilian.Bielohuby@sanofi.com.|R&D Diabetes Division/Insulin Biology, Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, Bldg. H821, 65926, Frankfurt am Main, Germany. Maximilian.Bielohuby@sanofi.com.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bielohuby
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001842:Bone and Bones / Q000502:physiology*; D050528:Diet, Carbohydrate-Restricted; D059305:Diet, High-Fat; D018753:Diet, Protein-Restricted; D004958:Estradiol / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D010012:Osteogenesis; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D012739:Gonadal Steroid Hormones; D020738:Leptin; D008055:Lipids; D010446:Peptide Fragments; D011347:Procollagen; D012709:Serum Albumin; C047202:procollagen Type I N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Bone mineral density; Growth hormone; Insulin-like growth factor-I; Ketogenic diet; Nutrition; Sex hormones