title: Mice long-term high-fat diet feeding recapitulates human cardiovascular alterations: an animal model to study the early phases of diabetic cardiomyopathy.
abstract: OBJECTIVE
  Hypercaloric diet ingestion and sedentary lifestyle result in obesity. Metabolic syndrome is a cluster of clinical features secondary to obesity, considered as a pre-diabetic condition and recognized as an independent risk factor for cardiovascular diseases. To better understand the relationship between obesity, metabolic syndrome and cardiovascular disease as well as for the development of novel therapeutic strategies, animal models that reproduce the etiology, course and outcomes of these pathologies are required. The aim of this work was to characterize the long-term effects of high-fat diet-induced obesity on the mice cardiovascular system, in order to make available a new animal model for diabetic cardiomyopathy.
  
  
  RESULTS
  Male C57BL/6 mice were fed with a standardized high-fat diet (obese) or regular diet (normal) for 16 months. Metabolic syndrome was evaluated testing plasma glucose, triglycerides, cholesterol, insulin, and glucose tolerance. Arterial pressure was measured using a sphygmomanometer (non invasive method) and by hemodynamic parameters (invasive method). Cardiac anatomy was described based on echocardiography and histological studies. Cardiac function was assessed by cardiac catheterization under a stress test. Cardiac remodelling and metabolic biomarkers were assessed by RT-qPCR and immunoblotting. As of month eight, the obese mice were overweight, hyperglycaemic, insulin resistant, hyperinsulinemic and hypercholesterolemic. At month 16, they also presented normal arterial pressure but altered vascular reactivity (vasoconstriction), and cardiac contractility reserve reduction, heart mass increase, cardiomyocyte hypertrophy, cardiac fibrosis, and heart metabolic compensations. By contrast, the normal mice remained healthy throughout the study.
  
  
  CONCLUSIONS
  Mice fed with a high-fat diet for prolonged time recapitulates the etiology, course and outcomes of the early phases of human diabetic cardiomyopathy.
authors.affiliation: Instituto de Ciencias, Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile. scalligaris@udd.cl
authors.forename: Sebastián D
authors.initials: SD
authors.lastname: Calligaris
authors.forename: Manuel
authors.initials: M
authors.lastname: Lecanda
authors.forename: Felipe
authors.initials: F
authors.lastname: Solis
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ezquer
authors.forename: Jaime
authors.initials: J
authors.lastname: Gutiérrez
authors.forename: Enrique
authors.initials: E
authors.lastname: Brandan
authors.forename: Andrea
authors.initials: A
authors.lastname: Leiva
authors.forename: Luis
authors.initials: L
authors.lastname: Sobrevia
authors.forename: Paulette
authors.initials: P
authors.lastname: Conget
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017931:DNA Primers / Q000235:genetics; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000503:physiopathology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004562:Electrocardiography; D015151:Immunoblotting; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers