title: Diet and gene interactions influence the skeletal response to polyunsaturated fatty acids.
abstract: Diets rich in omega-3s have been thought to prevent both obesity and osteoporosis. However, conflicting findings are reported, probably as a result of gene by nutritional interactions. Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor that improves insulin sensitivity but causes weight gain and bone loss. Fish oil is a natural agonist for PPARγ and thus may exert its actions through the PPARγ pathway. We examined the role of PPARγ in body composition changes induced by a fish or safflower oil diet using two strains of C57BL/6J (B6); i.e. B6.C3H-6T (6T) congenic mice created by backcrossing a small locus on Chr 6 from C3H carrying 'gain of function' polymorphisms in the Pparγ gene onto a B6 background, and C57BL/6J mice. After 9months of feeding both diets to female mice, body weight, percent fat and leptin levels were less in mice fed the fish oil vs those fed safflower oil, independent of genotype. At the skeletal level, fish oil preserved vertebral bone mineral density (BMD) and microstructure in B6 but not in 6T mice. Moreover, fish oil consumption was associated with an increase in bone marrow adiposity and a decrease in BMD, cortical thickness, ultimate force and plastic energy in femur of the 6T but not the B6 mice. These effects paralleled an increase in adipogenic inflammatory and resorption markers in 6T but not B6. Thus, compared to safflower oil, fish oil (high ratio omega-3/-6) prevents weight gain, bone loss, and changes in trabecular microarchitecture in the spine with age. These beneficial effects are absent in mice with polymorphisms in the Pparγ gene (6T), supporting the tenet that the actions of n-3 fatty acids on bone microstructure are likely to be genotype dependent. Thus caution must be used in interpreting dietary intervention trials with skeletal endpoints in mice and in humans.
authors.affiliation: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva 14, Switzerland. Electronic address: nicolas.bonnet@unige.ch.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bonnet
authors.affiliation: Service of Endocrinology, Diabetology, and Metabolism, Centre Hospitalier Universitaire Vaudois/Department of Physiology, Lausanne CH-1005, Switzerland; Division of Development and Growth, Department of Paediatrics, University of Geneva School of Medicine, 1211 Geneva 14, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Somm
authors.affiliation: Maine Medical Center Research Institute, Scarborough, ME 04074, USA.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Rosen
mesh_terms: D002001:Adipose Tissue, Brown / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002452:Cell Count; D004032:Diet; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D005395:Fish Oils / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D013131:Spine / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D013977:Tibia / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology
chemical_list: D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005395:Fish Oils
keywords: Aging; Bone microCT; Bone-fat interactions; Genetic animal models; Omega-3s
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