title: High dietary fat and the development of osteoarthritis in a rabbit model.
abstract: OBJECTIVE
  Osteoarthritis (OA) is associated with obesity, although this relationship remains unclear. Proposed etiologies of OA in obesity include mechanical loading of malaligned joints and possible toxicity of dietary fat. The hypothesis tested in the present study was that increased dietary fat worsens OA in both malaligned and normal joints, detected by biochemical and histological cartilage markers.
  
  
  METHODS
  83 New Zealand white rabbits were divided among two conditions related to OA: bowing of the knee and a 14%kcal vs 47.8%kcal fat diet. Rabbit weights and knee angles were compared throughout the experiment. At 28 and 38 weeks, intra-articular forces were measured, animals sacrificed, and knee cartilage examined for histological changes, glycosaminoglycan content, 35S uptake, and aggrecanase-1 expression.
  
  
  RESULTS
  There were no differences in animal weights or intra-articular forces between the two diets. Despite increased fat content in their diet, animals on the 47.8%kcal fat diet did not gain excess weight. Representative histology showed atypical shearing of articular cartilage among animals on the high fat diet. Animals on the 47.8%kcal fat diet had suppression of protein synthesis compared to the 14%kcal fat diet: lower glycosaminoglycan content and aggrecanase-1 expression in all knee compartments at both times, and lower 35S uptake at 38 weeks.
  
  
  CONCLUSIONS
  These results suggest dietary fat, independent of animal weight, results in altered chondrocyte function. Increased dietary fat was associated with changes in rabbit cartilage in vivo and appears to be a risk factor for the development of OA.
authors.affiliation: Department of Orthopaedics, Rhode Island Hospital and Brown University, Providence, RI, USA. abrunner@partners.org
authors.forename: A M
authors.initials: AM
authors.lastname: Brunner
authors.forename: C M
authors.initials: CM
authors.lastname: Henn
authors.forename: E I
authors.initials: EI
authors.lastname: Drewniak
authors.forename: A
authors.initials: A
authors.lastname: Lesieur-Brooks
authors.forename: J
authors.initials: J
authors.lastname: Machan
authors.forename: J J
authors.initials: JJ
authors.lastname: Crisco
authors.forename: M G
authors.initials: MG
authors.lastname: Ehrlich
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002358:Cartilage, Articular / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D006025:Glycosaminoglycans / Q000378:metabolism; D010003:Osteoarthritis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D011817:Rabbits; D013314:Stress, Mechanical; D013462:Sulfur Radioisotopes / Q000493:pharmacokinetics; D015430:Weight Gain
chemical_list: D006025:Glycosaminoglycans; D013462:Sulfur Radioisotopes; D051722:ADAM Proteins; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein