| Popis: |
The prevalence and increasing incidences of obesity and obesity-related illnesses are not limited to westernized countries, but exist as a global epidemic impacting the health of adults and children. According to the WHO, over 1 billion adults are overweight (BMI > 25 kg/m2) and approximately one-third of this population has been diagnosed as clinically obese (BMI > 30 kg/m2). Causality between obesity and metabolic disorders (such as type 2 diabetes), cancer, cardiovascular diseases and liver diseases have been investigated using a variety of in vitro and in vivo models, including genetically engineered mice. The overall purpose of the current study was to fully characterize a genetically intact mouse of obesity for evidence of type II diabetes using clinical and anatomical pathology examination. Male C57Bl/6J mice were fed either a control diet or one in which 60% kcal were due to lard as early as 5 weeks of age and maintained on either diet through age 30 weeks. During the study, body weight and body fat measurements were obtained and complete necropsy was performed on mice at 15, 20, 30, and 40 weeks of age. Mice physiology was assessed and characterized through the analysis of serum chemistry (glucose, cholesterol, triglycerides, insulin, and leptin), histopathologic evaluation of tissues, and determination of hepatic and renal function. Significant increases in both body weight and body fat percentages were determined in male mice fed the high-fat diet vs. age-matched littermates consuming the control diet at 15, 20, 30, and 40 weeks. In concert with increased body weight and body fat %, serum cholesterol concentrations were significantly elevated throughout the study in obese vs. mice fed the control-diet. Serum insulin levels were ≥ 4-fold higher in obese vs. controldiet fed mice by ages 30 and 40 weeks. 100% of male mice on the high fat diet developed hepatic lipidosis (steatosis) by age 30 weeks with subsequent inflammation (steatohepatitis) by age 40 weeks. Obese male mice also exhibited mesangial cell and matrix proliferation (minimal to moderate) by 30 and 40 weeks of age. Notably, similar hepatic and renal lesions have been identified in humans with obesity-related illnesses, non-alcoholic fatty liver disease (NAFLD) and/or type II diabetes. The current genetically intact animal model may prove valuable in achieving the obesity phenotype in a manner appropriate to the onset of obesity and obesity-related diseases in humans. |
