title: The Murphy Roths Large (MRL) mouse strain is naturally resistant to high fat diet-induced hyperglycemia.
abstract: OBJECTIVE
  Due to their previously identified naturally and chronically increased levels of skeletal muscle pAMPK we hypothesized and now investigated whether the MRL/MpJ (MRL) mice would be resistant to high fat diet (HFD)-induced metabolic changes.
  
  
  METHODS
  Three-week old male MRL and control C57Bl/6 (B6) mice were randomly assigned to 12weeks of high fat diets (HFD) or control diets (CD). Weekly animal masses and fasting blood glucose measurements were acquired. During the last week of diet intervention, fasted animals were subjected to glucose and insulin tolerance tests. At harvest, tissues were dissected for immunoblots and serum was collected for ELISA assays.
  
  
  RESULTS
  The MRL mouse strain is known for its ability to regenerate ear punch wounds, cardiac cryoinjury, and skeletal muscle disease. Despite gaining weight and increasing their fat deposits the MRL mice were resistant to all other indicators of HFD-induced metabolic alterations assayed. Only the HFD-B6 mice displayed fasting hyperglycemia, hyperinsulinemia and hypersensitivity to glucose challenge. HFD-MRL mice were indistinguishable from their CD-MRL counterparts in these metrics. Skeletal muscles from the HFD-MRL contained heightened levels of pAMPK, even above their CD counterparts.
  
  
  CONCLUSIONS
  The MRL mouse strain is the first naturally occurring mouse strain that we are aware of that is resistant to HFD-induced metabolic changes. Furthermore, the increased pAMPK suggests a proximal mechanism for these beneficial metabolic differences. We further hypothesize that these metabolic differences and plasticity provide the basis for the MRL mouse strain's super healing characteristics. This project's ultimate aim is to identify novel therapeutic targets, which specifically increase pAMPK.
authors.affiliation: Department of Physiology and Biophysics, The University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Mull
authors.affiliation: Department of Physiology and Biophysics, The University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Tirsit K
authors.initials: TK
authors.lastname: Berhanu
authors.affiliation: Department of Physiology and Biophysics, The University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Roberts
authors.affiliation: Department of Physiology and Biophysics, The University of Illinois at Chicago, Chicago, IL 60612, USA.|Center for Cardiovascular Research, The University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Ahlke
authors.initials: A
authors.lastname: Heydemann
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D018149:Glucose Intolerance / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008815:Mice, Inbred Strains; D010766:Phosphorylation
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D008055:Lipids; C495693:Slc2a4 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Animal model; Genetic resistance; High fat diet; Skeletal muscle metabolism