title: Tendon repair is compromised in a high fat diet-induced mouse model of obesity and type 2 diabetes.
abstract: BACKGROUND
  The obesity epidemic has resulted in a large increase in type 2 diabetes (T2D). While some secondary complications of T2D are well recognized and their cellular and molecular mechanisms are defined, the impact of T2D on the musculoskeletal system is less understood. Clinical evidence suggests that tendon strength and repair are compromised. Here, a mouse model of obesity and T2D recapitulates the deleterious effects of this condition on tendon repair.
  
  
  METHODS
  Male C57BL/6J mice at 5 weeks of age were placed on a high fat (HF)(60% kcal) or low fat (10% kcal) diet for 12 weeks. The flexor digitorum longus (FDL) tendon was then injured by puncturing it with a beveled needle. Progression of FDL tendon healing was assessed through biomechanical and histological analysis at 0, 7, 14 and 28 days post-injury.
  
  
  RESULTS
  HF-fed mice displayed increased body weight and elevated fasting glucose levels, both consistent with T2D. No differences in biomechanical properties of the uninjured FDL tendon were observed after 12 weeks on HF versus lean diets, but decreased maximum force in uninjured tendons from HF-fed mice was observed at 24 weeks. Following puncture injury, tendons from HF-fed mice displayed impaired biomechanical properties at day 28 post injury. In support of defective repair in the HF-fed mice, histological examination of the injury site showed a smaller area of repair and lower cell content in the repair area of HF-fed mice. Insulin receptors were expressed in most cells at the injury site regardless of diet.
  
  
  CONCLUSIONS
  The HF-diet mouse model of obesity and T2D reproduces the impaired tendon healing that is observed in this patient population. The exact mechanism is unknown, but we hypothesize that a cellular defect, perhaps involving insulin resistance, leads to decreased proliferation or recruitment to the injury site, and ultimately contributes to defective tendon healing.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, United States of America; Department of Biomedical Engineering, University of Rochester, Rochester, New York, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: David
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Khyrie H
authors.initials: KH
authors.lastname: Jones
authors.affiliation: Department of Biomedical Engineering, University of Rochester, Rochester, New York, United States of America.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Inzana
authors.affiliation: Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zuscik
authors.affiliation: Department of Biomedical Engineering, University of Rochester, Rochester, New York, United States of America; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Hani A
authors.initials: HA
authors.lastname: Awad
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, United States of America; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Mooney
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001786:Blood Glucose; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism; D059305:Diet, High-Fat; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D013708:Tendon Injuries / Q000473:pathology*; D014945:Wound Healing
chemical_list: D001786:Blood Glucose