Mechanisms of obesity and related pathologies: Role of apolipoprotein E in the development of obesity

Abstract

Apolipoprotein E is a polymorphic glycoprotein in humans with a molecular mass of 34.5 kDa. It is a component of chylomicron remnants, very low density lipoprotein, low density lipoprotein and high density lipoprotein, and is primarily responsible for maintaining plasma lipid homeostasis. In addition to these well‐documented functions, recent studies in experimental mouse models, as well as population studies, show that apolipoprotein E also plays an important role in the development of obesity and insulin resistance. It is widely accepted that disruption in homeostasis between food intake and energy expenditure, and the subsequent deposition of excess fatty acids into fat cells in the form of triglycerides, leads to the development of obesity. Despite the pivotal role of obesity and dyslipidemia in the development of the metabolic syndrome and heart disease, the functional interactions between adipose tissue and components of the lipoprotein transport system have not yet been investigated thoroughly. In this minireview, we focus on the current literature pertinent to the involvement of apolipoprotein E in the development of pathologies associated with the metabolic syndrome.

The low density lipoprotein receptor modulates the effects of hypogonadism on diet-induced obesity and related metabolic perturbations

“…As shown in Fig. 3D , exemestane-treated accumulation and improved glucose metabolism in mice and humans ( 21,22,32,33 ( Fig. 4A ), a fi nding that coincides with the reduced body fat accumulation obtained in TD Ldlr Ϫ / Ϫ mice.…”

“…Recent studies by us and others have suggested that the lipoprotein metabolic pathway is a pivotal contributor to the development of obesity and related metabolic dysfunctions in experimental mice. Specifi cally, mice deficient in ApoE, a key protein in the clearance of chylomicron remnants, LDL, and VLDL in plasma, are resistant to diet-induced obesity, insulin resistance, and glucose intolerance ( 21,22 ), while knock-in ApoE3 transgenic mice are sensitized toward these conditions ( 21 ). Similarly, expression levels of LDL receptor-related protein 1 (Lrp1), a member of the LDL receptor (Ldlr) superfamily that binds lipoprotein-associated ApoE modulates the development of obesity and its related metabolic perturbations mainly by regulating the fl ux of dietary TGs to hepatic and adipose tissues and the energy expenditure (EE) of the tested mice ( 23 ).…”

A genetic risk tool for obesity predisposition assessment and personalized nutrition implementation based on macronutrient intake

“…APOE gene encodes for a major structural apolipoprotein of several lipoprotein classes (chylomicrons, very low-density lipoprotein-VLDL-and HDL), which plays diverse roles in lipoprotein metabolism. Polymorphisms in APOE have been previously related with lipid metabolism disorders, cardiovascular disease, Alzheimer's disease and obesity phenotype (Sima et al 2007;Kypreos et al 2009;Ridge et al 2013). Although a large number of studies have observed the association between APOE genotypes and obesity, up to date, no study has found any statistically significant association between rs429358 and obesity phenotype (Clark et al 2009).…”

Impact of Genetic Polymorphisms on Insulin Resistance

“…However, a number of studies with experimental mouse models have shown that apoE also has an important role in the development of obesity and insulin resistance (Kypreos et al, 2009;Gao et al, 2007). ApoE is involved in excess fat accumulation and energy metabolism, including the regulation of food intake and energy expenditure.…”