title: The PPARα Agonist Fenofibrate Improves the Musculoskeletal Effects of Exercise in Ovariectomized Rats.
abstract: The musculoskeletal effects of exercise are attenuated by estrogen deficiency. The peroxisome proliferator-activated receptor-α agonist fenofibrate exerts beneficial effects in bone and muscle. We therefore examined whether fenofibrate could enhance the musculoskeletal training response during estrogen deficiency. We investigated the combined effects of 8 weeks of fenofibrate and jumping exercise in ovariectomized (OVX) Sprague Dawley rats. Female rats were allocated to a sham-operated group and four OVX groups; fenofibrate (OVX-Fen), exercise (OVX-Ex), combined fenofibrate and exercise (OVX-FenEx), and a control group (OVX-Ctr) (n = 12/group). Fenofibrate (90 mg/kg/d) or methylcellulose was given by gavage. The combination of exercise and fenofibrate resulted in enhanced femoral bone mineral density (BMD) and improved bone microarchitecture compared with fenofibrate alone as well as increased trabecular BMD compared with OVX-Ctr. These effects were not seen in the OVX-Ex group. Femoral BMD was normalized in both exercise groups relative to sham and increased more in all intervention groups compared with OVX-Ctr. A higher plasma level of the bone formation marker type 1 collagen amino propeptide was observed in the OVX-Fen and OVX-FenEx groups compared with controls. Lean mass and soleus muscle weight were higher in the OVX-FenEx group than in the OVX-Ctr group, which coincided with lower mRNA levels of Atrogin1. These results suggest that peroxisome proliferator-activated receptor-α activation improves the musculoskeletal effects of exercise during estrogen deficiency.
authors.affiliation: Department of Cancer Research and Molecular Medicine (M.P.M., U.S., A.K.S.), Norwegian University of Science and Technology, N-7491 Trondheim, Norway; Department of Medical Biosciences and Physiological Chemistry (M.E.), Umeå University, SE-901 87 Umeå, Sweden; and Department of Biomedical Sciences (R.G.E., C.S.), University of Veterinary Medicine Vienna, A-1210 Vienna, Austria; and Department of Endocrinology (U.S.), St Olav's University Hospital HF, N-7006 Trondheim, Norway.
authors.forename: Mats Peder
authors.initials: MP
authors.lastname: Mosti
authors.affiliation: Department of Cancer Research and Molecular Medicine (M.P.M., U.S., A.K.S.), Norwegian University of Science and Technology, N-7491 Trondheim, Norway; Department of Medical Biosciences and Physiological Chemistry (M.E.), Umeå University, SE-901 87 Umeå, Sweden; and Department of Biomedical Sciences (R.G.E., C.S.), University of Veterinary Medicine Vienna, A-1210 Vienna, Austria; and Department of Endocrinology (U.S.), St Olav's University Hospital HF, N-7006 Trondheim, Norway.
authors.forename: Madelene
authors.initials: M
authors.lastname: Ericsson
authors.affiliation: Department of Cancer Research and Molecular Medicine (M.P.M., U.S., A.K.S.), Norwegian University of Science and Technology, N-7491 Trondheim, Norway; Department of Medical Biosciences and Physiological Chemistry (M.E.), Umeå University, SE-901 87 Umeå, Sweden; and Department of Biomedical Sciences (R.G.E., C.S.), University of Veterinary Medicine Vienna, A-1210 Vienna, Austria; and Department of Endocrinology (U.S.), St Olav's University Hospital HF, N-7006 Trondheim, Norway.
authors.forename: Reinhold G
authors.initials: RG
authors.lastname: Erben
authors.affiliation: Department of Cancer Research and Molecular Medicine (M.P.M., U.S., A.K.S.), Norwegian University of Science and Technology, N-7491 Trondheim, Norway; Department of Medical Biosciences and Physiological Chemistry (M.E.), Umeå University, SE-901 87 Umeå, Sweden; and Department of Biomedical Sciences (R.G.E., C.S.), University of Veterinary Medicine Vienna, A-1210 Vienna, Austria; and Department of Endocrinology (U.S.), St Olav's University Hospital HF, N-7006 Trondheim, Norway.
authors.forename: Christiane
authors.initials: C
authors.lastname: Schüler
authors.affiliation: Department of Cancer Research and Molecular Medicine (M.P.M., U.S., A.K.S.), Norwegian University of Science and Technology, N-7491 Trondheim, Norway; Department of Medical Biosciences and Physiological Chemistry (M.E.), Umeå University, SE-901 87 Umeå, Sweden; and Department of Biomedical Sciences (R.G.E., C.S.), University of Veterinary Medicine Vienna, A-1210 Vienna, Austria; and Department of Endocrinology (U.S.), St Olav's University Hospital HF, N-7006 Trondheim, Norway.
authors.forename: Unni
authors.initials: U
authors.lastname: Syversen
authors.affiliation: Department of Cancer Research and Molecular Medicine (M.P.M., U.S., A.K.S.), Norwegian University of Science and Technology, N-7491 Trondheim, Norway; Department of Medical Biosciences and Physiological Chemistry (M.E.), Umeå University, SE-901 87 Umeå, Sweden; and Department of Biomedical Sciences (R.G.E., C.S.), University of Veterinary Medicine Vienna, A-1210 Vienna, Austria; and Department of Endocrinology (U.S.), St Olav's University Hospital HF, N-7006 Trondheim, Norway.
authors.forename: Astrid Kamilla
authors.initials: AK
authors.lastname: Stunes
mesh_terms: D000818:Animals; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010052:Ovariectomy; D047493:PPAR alpha / Q000819:agonists*; D010805:Physical Conditioning, Animal; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: D004967:Estrogens; D047493:PPAR alpha; D011345:Fenofibrate