title: Hind limb ischemia-reperfusion injury in diet-induced obese mice.
abstract: BACKGROUND
  Obesity is a major risk factor for the development of diabetes. Limb ischemia-reperfusion injury (IR) is a common clinical problem in diabetics who have compromised lower extremity perfusion. This study compared the histologic, metabolic, and functional outcomes after hind limb IR in diet-induced obese (DIO) and non-diabetic (ND) mice during the acute and the regenerative phases of IR.
  
  
  METHODS
  DIO and ND mice were subjected to 1.5 h unilateral hind limb ischemia followed by 1- or 28-d IR. Muscle morphology, metabolic, and genomic stress were evaluated at days 1 and 28 IR; Acute inflammation and thrombosis were only measured at day-1 IR. At day 28, IR, skeletal muscle contractility, and maturation were also assessed.
  
  
  RESULTS
  At day-1 IR, similar levels of acute muscle fiber necrosis were seen in both groups. DIO mice demonstrated substantially greater inflammatory, prothrombotic, and genomic stress responses, which were also associated with a greater reduction in energy substrates and Akt phosphorylation. At 28d, there was no difference in the peak forces generated in the hind limbs for the two groups. DIO mice had reduced fatigue resistance compared with ND and larger areas of fat accumulation although there was no significant difference in muscle fiber maturation.
  
  
  CONCLUSIONS
  DIO mice had an exacerbated acute response to IR with enhanced metabolic deficit, fat accumulation, and defective functional recovery during the regenerative phase of IR. These changes in fatigue resistance reflect compromised functional recovery after IR injury and have relevance for the functional recovery of patients with metabolic syndrome and insulin resistance.
authors.affiliation: Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Vascular and Endovascular Surgery, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: albadawi1@msn.com.
authors.forename: Hassan
authors.initials: H
authors.lastname: Albadawi
authors.affiliation: Division of Vascular Imaging and Intervention, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Rahmi
authors.initials: R
authors.lastname: Oklu
authors.affiliation: Division of Vascular and Endovascular Surgery, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Cormier
authors.affiliation: Division of Vascular and Endovascular Surgery, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: O'Keefe
authors.affiliation: Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Center for Laryngeal Surgery and Voice Rehabilitation, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: James T
authors.initials: JT
authors.lastname: Heaton
authors.affiliation: Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Center for Laryngeal Surgery and Voice Rehabilitation, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: James B
authors.initials: JB
authors.lastname: Kobler
authors.affiliation: Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: William G
authors.initials: WG
authors.lastname: Austen
authors.affiliation: Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Vascular and Endovascular Surgery, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Watkins
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012038:Regeneration; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D013312:Stress, Physiological
chemical_list: D051057:Proto-Oncogene Proteins c-akt
keywords: Diabetes; Diet-induced obesity; Inflammation; Insulin resistance; Limb ischemia; Metabolism; Muscle contraction; Muscle regeneration; Phosphoinositide-3-kinase–protein kinase B/Akt pathway; Reperfusion injury