title: Combined high-fat-resveratrol diet and RIP140 knockout mice reveal a novel relationship between elevated bone mitochondrial content and compromised bone microarchitecture, bone mineral mass, and bone strength in the tibia.
abstract: While resveratrol (RSV) is associated with the prevention of high-fat (HF) diet-induced insulin resistance, the effects on bone health combined with an HF-diet is unknown. Therefore, we determined the effect of RSV on bone microarchitecture in the presence of an HF-diet, while also elucidating molecular adaptations within bone that could contribute to bone health status.
  
  
  
  Male C57BL6 mice were provided control (10% fat) or HF-diet (60% fat) in the presence or absence of RSV for 12 weeks. While RSV prevented HF diet-induced glucose intolerance, HF-RSV compromised tibial microarchitecture, mineral mass, and strength. The compromised outcomes following HF-RSV corresponded with higher markers of osteoclast-activation and bone-resorption (decreased OPG/RANKL ratio; increased cathepsin K), as well as higher markers of tibial mitochondrial content. A molecular model of elevated mitochondrial content (RIP140 knock out (KO) mice) was utilized to determine proof-of-principle that increasing mitochondrial content coincides with decrements in bone health. RIP140 KO mice displayed higher markers of mitochondrial content, and similar to HF-RSV, had compromised bone microarchitecture, lower BMD/strength, and higher markers of osteoclast-activation/bone-resorption.
  
  
  
  These data show that in the presence of an HF-diet, RSV negatively alters bone health, a process associated with increased mitochondrial content and markers of bone resorption.
authors.affiliation: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada. pmiotto@uoguelph.ca.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Miotto
authors.affiliation: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Frendo-Cumbo
authors.affiliation: Department of Kinesiology and Centre for Bone and Muscle Health, Brock University, Ontario, Canada.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Sacco
authors.affiliation: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: David C
authors.initials: DC
authors.lastname: Wright
authors.affiliation: Department of Kinesiology and Centre for Bone and Muscle Health, Brock University, Ontario, Canada.
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Ward
authors.affiliation: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Graham P
authors.initials: GP
authors.lastname: Holloway
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy; D059305:Diet, High-Fat / Q000009:adverse effects*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D000078723:Nuclear Receptor Interacting Protein 1; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013977:Tibia / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D053245:RANK Ligand; D013267:Stilbenes; C505689:Tnfsf11 protein, mouse; D000077185:Resveratrol
keywords: Bone health; Bone turnover; Mitochondria; Resveratrol; Type 2 diabetes