Impact of apoE genotype on oxidative stress, inflammation and disease risk. Mol Nutr Food Res 52:131-145 ([IF: 4.909])

Institute of Human Nutrition and Food Science, Christian Albrechts University of Kiel, Kiel, Germany.
Molecular Nutrition & Food Research (Impact Factor: 4.6). 01/2008; 52(1):131-45. DOI: 10.1002/mnfr.200700322
Source: PubMed


Although in developing countries an apolipoprotein E4 (apoE4) genotype may offer an evolutionary advantage, as it has been shown to offer protection against certain infectious disease, in Westernised societies it is associated with increased morbidity and mortality, and represents a significant risk factor for cardiovascular disease, late-onset Alzheimer's disease and other chronic disorders. ApoE is an important modulator of many stages of lipoprotein metabolism and traditionally the increased risk was attributed to higher lipid levels in E4 carriers. However, more recent evidence demonstrates the multifunctional nature of the apoE protein and the fact that the impact of genotype on disease risk may be in large part due to an impact on oxidative status or the immunomodulatory/anti-inflammatory properties of apoE. An increasing number of studies in cell lines, targeted replacement rodents and human volunteers indicate higher oxidative stress and a more pro-inflammatory state associated with the epsilon4 allele. The impact of genotype on the antioxidant and immunomodulatory/anti-inflammatory properties of apoE is the focus of the current review. Furthermore, current information on the impact of environment (diet, exercise, smoking status, alcohol) on apoE genotype-phenotype associations are discussed with a view to identifying particular lifestyle strategies that could be adapted to counteract the 'at-risk' E4 genotype.

Download full-text


Available from: Gerald Rimbach, Jan 30, 2015
  • Source
    • "Although effects of famine on the human gene pool are considered exaggerated [49] an advantage for individuals carrying an APOE allele that favours fatty acid deposition and curbs fatty acid mobilization and energy dissipation to save adipose tissue energy stores – such as ε3 -may be reasonable. However, other factors including differences in fertility or reproductive success [50], traumatic head injury outcome [51] and inflammatory processes and therefore ability to combat infectious diseases [52] may also have contributed to the universal spread of the ɛ3 allele. "
    [Show abstract] [Hide abstract]
    ABSTRACT: ScopeOf the three human apolipoprotein E (APOE) alleles, the ε3 allele is most common, which may be a result of adaptive evolution. In this study, we investigated whether the APOE genotype affects body weight and energy metabolism through regulation of fatty acid utilization.Methods and resultsTargeted replacement mice expressing the human APOE3 were significantly heavier on low- and high-fat diets compared to APOE4 mice. Particularly on high-fat feeding, food intake and dietary energy yields as well as fat mass were increased in APOE3 mice. Fatty acid mobilization determined as activation of adipose tissue lipase and fasting plasma nonesterified fatty acid levels were significantly lower in APOE3 than APOE4 mice. APOE4 mice, in contrast, exhibited higher expression of proteins involved in fatty acid oxidation in skeletal muscle.Conclusion Our data suggest that APOE3 is associated with the potential to more efficiently harvest dietary energy and to deposit fat in adipose tissue, while APOE4 carriers tend to increase fatty acid mobilization and utilization as fuel substrates especially under high-fat intake. The different handling of dietary energy may have contributed to the evolution and worldwide distribution of the ε3 allele.
    Molecular Nutrition & Food Research 11/2014; 59(2). DOI:10.1002/mnfr.201400636 · 4.60 Impact Factor
  • Source
    • "This suggests that even very small concentrations of curcumin or curcumin metabolites below the analytical detection limit may induce effects on the molecular level (neuro-or mitohormesis) and account for the observed neuroprotective effects (Mattson and Cheng 2006; Calabrese et al. 2010). The apolipoprotein (APO) E4 allele is a major genetic risk factor for sporadic or late-onset AD (Strittmatter and Roses 1996; Jofre-Monseny et al. 2008). APOE is involved in the distribution and cellular uptake of cholesterol and is the major apolipoprotein in the brain (Huebbe et al. 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Curcumin from Curcuma longa may exert putative neuroprotective properties in the brain. Impaired mitochondrial function is implicated in Alzheimer's disease and the presence of the apolipoprotein (APO) E4 genotype, which is a risk factor for late-onset Alzheimer's disease, may aggravate mitochondrial malfunction. Here, we report that in the brain of 16-month-old APOE4-targeted replacement mice, adenosine triphosphate (ATP) concentrations were significantly lower than in APOE3 mice. A 3-month dietary supplementation of 0.2 % curcumin numerically increased ATP concentrations in APOE3 and significantly in APOE4 mice compared to the respective controls. Curcumin significantly induced the transcription of peroxisome proliferator-activated receptor (PPAR) γ and mitochondrial transcription factor A (TFAM) in APOE3, but not in APOE4 mice. Moreover, PPARγ coactivator (PGC)-1α and guanine-adenine repeat binding protein α (GABPa) mRNA was only increased in APOE3 mice. Consistent with these observations, protein expression of mitochondrial respiratory complexes, especially of complex IV, also appeared to be increased in APOE3 mice. In conclusion, we provide evidence that curcumin affects mitochondrial function and gene and protein expression in the murine brain despite its low bioavailability and carriers of the Alzheimer's disease-risk genotype APOE4 may be less responsive to dietary curcumin than APOE3 carriers.
    Genes & Nutrition 05/2014; 9(3):397. DOI:10.1007/s12263-014-0397-3 · 2.79 Impact Factor
  • Source
    • "This was originally attributed to elevated blood lipid levels in this subgroup [4]. However , the mechanisms that relate APOE4 to increased CVD risk may be more complex than solely a lipid effect [1] [2] with studies largely conducted in transgenic animals or cell lines indicating that the APOE4 allele is related to a more pro-oxidative and pro-inflammatory state compared with the APOE3 allele [1] [2]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Apolipoprotein E (APOE) genotype is believed to play an important role in cardiovascular risk. APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. Blood samples were collected from a subset of SATgenε participants (n = 52/88), prospectively recruited according to APOE genotype (n = 26 E3/E3 and n = 26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45 g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24 h with either 0.05 or 1 μg/ml of bacterial lipopolysaccharide (LPS). Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P < 0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P < 0.05). In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects.
    Cytokine 04/2014; 66(2). DOI:10.1016/j.cyto.2013.12.015 · 2.66 Impact Factor
Show more