Generation and characterization of two novel mouse models exhibiting the phenotypes of the metabolic syndrome: Apob48−/−Lepob/ob mice devoid of ApoE or Ldlr

The metabolic syndrome is a group of disorders including obesity, insulin resistance, atherogenic dyslipidemia, hyperglycemia, and hypertension. To date, few animal models have been described to recapitulate the phenotypes of the syndrome. In this study, we generated and characterized two lines of triple-knockout mice that are deficient in either apolipoprotein E (Apoe−/−) or low-density lipoprotein receptor (Ldlr−/−) and express no leptin (Lepob/ob) or apolipoprotein B-48 but exclusively apolipoprotein B-100 (Apob100/100). These two lines are referred to as Apoe triple-knockout-Apoe 3KO (Apoe−/−Apob100/100Lepob/ob) and Ldlr triple-knockout-Ldlr 3KO (Ldlr−/−Apob100/100Lepob/ob) mice. Both lines develop obesity, hyperinsulinemia, hyperlipidemia, hypertension, and atherosclerosis. However, only Apoe 3KO mice are hyperglycemic and glucose intolerant and are more obese than Ldlr 3KO mice. To evaluate the utility of these lines as pharmacological models, we treated both with leptin and found that leptin therap...