LDL receptor but not apolipoprotein E deficiency increases diet-induced obesity and diabetes in mice

Abstract

The aim of this study was to determine whether phenotypes associated with type 2 diabetes are altered in dyslipidemic obese mice. C57BL/6 wild-type, low-density lipoprotein (LDL) receptor-deficient (LDLR-/-), and apolipoprotein E-deficient (apoE-/-) mice were fed a high-fat, high-carbohydrate diet (diabetogenic diet), and the development of obesity, diabetes, and hypertriglyceridemia was examined. Wild-type mice became obese and developed hyperglycemia, but not hypertriglyceridemia, in response to this diet. LDLR-/- mice fed the diabetogenic diet became more obese than wild-type mice and developed severe hypertriglyceridemia and hyperleptinemia. Surprisingly, glucose levels were only modestly higher and insulin levels and insulin-to-glucose ratios were not strikingly different from those of wild-type mice. In contrast, diabetogenic diet-fed apoE-/- mice were resistant to changes in glucose and lipid homeostasis despite becoming obese. These data suggest that modifications in lipoprotein profiles associated with loss of the LDL receptor or apoE function have profound and unique consequences on susceptibility to diet-induced obesity and type 2 diabetic phenotypes.

Comparison of 99mTc-annexin A5 with 18F-FDG for the detection of atherosclerosis in ApoE−/− mice

“…Intramural bleeding was also reportedly observed in the brachiocephalic arteries at an older age (60 weeks old) possibly caused by plaque rupture [43]. that apoE -/-mice were resistant to developing hyperglycemia in response to high-fat, even diabetogenic diet [44]. In fact, the plasma glucose levels in our apoE -/-mice were within a normal range.…”

Diet-Induced Increases in Adiposity, but Not Plasma Lipids, Promote Macrophage Infiltration Into White Adipose Tissue

“…Like wild-type mice, LDL receptor (LDLR) Ϫ/Ϫ mice are susceptible to dietinduced obesity and insulin resistance. In addition, they also develop hyperlipidemia (21,22), making them a useful model in which to study the physiological consequences of combined obesity and hyperlipidemia. The A y /a;LDLR Ϫ/Ϫ mice were produced by intercrossing obesity-prone agouti yellow mice (A y /a) with LDLR Ϫ/Ϫ mice.…”

Diabetic Vascular Disease

“…Introduction of cholesterol ester This model also is amenable to diet induced insulin resistance and hyperglycemia. 91 Insulin resistance by itself did not alter lesion area. 92 In other studies diabetic LDL receptor knockout mice developed more lesions associated with a marked increase in plasma cholesterol.…”