APOE genotype influences insulin resistance, apolipoprotein CII and CIII according to plasma fatty acid profile in the Metabolic Syndrome

Fallaize, Rosalind; Carvalho-Wells, A. L.; Tierney, Audrey C.; Marı́n, Carmen; Kieć‐Wilk, Beata; Dembińska-Kieć, A.; Drevon, Christian A.; Defoort, Catherine; López‐Miranda, José; Risérus, Ulf; Blaak, Ellen E.; Roche, Helen M.; Lovegrove, Julie A.

doi:10.1038/s41598-017-05802-2

Cited by 35 publications

(22 citation statements)

References 62 publications

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“…Despite evidence to link APOE4 with insulin resistance and metabolic syndrome [ 30 , 31 ], the present study found no significant associations between APOE genotype or carriage of E4 and Si. There were also no interactions between APOE genotype and diet for insulin response and secretion, which has been reported previously in E4 carriers on a high SFA diet and linked to insulin resistance [ 9 ].…”

Section: Discussionsupporting

confidence: 68%

“…The common APOE polymorphism has been shown to account for up to 7% of variation in total serum cholesterol (TC) and LDL-C in populations [ 8 ]. APOE4 genotype (carriage of ε4 alleles) has also been linked to insulin resistance and the metabolic syndrome [ 9 , 10 ], and increased risk of coronary heart disease mortality [ 11 , 12 , 13 ]. In contrast, the extent to which APOE genotype contributes to variation in LDL-C in response to the reduction of SFA is less clear.…”

Section: Introductionmentioning

confidence: 99%

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APOE4 Genotype Exerts Greater Benefit in Lowering Plasma Cholesterol and Apolipoprotein B than Wild Type (E3/E3), after Replacement of Dietary Saturated Fats with Low Glycaemic Index Carbohydrates

et al. 2018

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We examined the impact of APOE genotype on plasma lipids and glucose in a secondary analysis of data from a five-arm, randomised controlled, parallel dietary intervention trial (‘RISCK’ study), to investigate the impact of replacing saturated fatty acids (SFA) with either monounsaturated fat (MUFA) or carbohydrate of high or low glycaemic index (GI) on CVD risk factors and insulin sensitivity. We tested the impact of APOE genotype (carriage of E2 and E4 alleles versus E3/E3), determined retrospectively, on plasma lipids, lipoproteins and glucose homeostasis at baseline (n = 469), and on the change in these variables after 24 weeks of dietary intervention (n = 389). At baseline, carriers of E2 (n = 70), E4 (n = 125) and E3/E3 (n = 274) expressed marked differences in total plasma cholesterol (TC, p = 0.001), low density lipoprotein cholesterol (LDL-C, p < 0.0001), apolipoprotein B (apo B, p < 0.0001) and total to high density lipoprotein cholesterol ratio (TC:HDL-C, p = 0.002), with plasma concentrations decreasing in the order E4 > E3/E3 > E2. Following intervention, there was evidence of a significant diet x genotype interaction with significantly greater decreases in TC (p = 0.02) and apo B (p = 0.006) among carriers of E4 when SFA was replaced with low GI carbohydrate on a lower fat diet (TC −0.28 mmol/L p = 0.03; apo B −0.1 g/L p = 0.02), and a relative increase in TC (in comparison to E3/E3) when SFA was replaced with MUFA and high GI carbohydrates (TC 0.3 mmol/L, p = 0.03). Among carriers of E2 (compared with E3/E3) there was an increase in triacylglycerol (TAG) when SFA was replaced with MUFA and low GI carbohydrates 0.46 mmol/L p = 0.001). There were no significant interactions between APOE genotype and diet for changes in indices of glucose homeostasis. In conclusion, variations in APOE genotype led to differential effects on the lipid response to the replacement of SFA with MUFA and low GI carbohydrates.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

APOE4 Genotype Exerts Greater Benefit in Lowering Plasma Cholesterol and Apolipoprotein B than Wild Type (E3/E3), after Replacement of Dietary Saturated Fats with Low Glycaemic Index Carbohydrates

et al. 2018

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“…ApoE is involved in many steps of lipoprotein homeostasis including triglyceride-rich VLDL and chylomicron remnants as well as subset of HDL particles 50 . Previous studies have shown that ApoE is not only important for fat accumulation, but is also linked with mechanisms of insulin resistance and the development of the metabolic syndrome [51][52][53] . ApoE has a wide tissue distribution and function 54 .…”

Section: Discussionmentioning

confidence: 99%

Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics

Valsesia

Chakrabarti

Hager

et al. 2020

Sci Rep

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Weight loss aims to improve glycemic control in obese but strong variability is observed. Using a multiomics approach, we investigated differences between 174 responders and 201 non-responders, that had lost >8% body weight following a low-caloric diet (LCD, 800 kcal/d for 8 weeks). The two groups were comparable at baseline for body composition, glycemic control, adipose tissue transcriptomics and plasma ketone bodies. But they differed significantly in their response to LCD, including improvements in visceral fat, overall insulin resistance (IR) and tissue-specific IR. Transcriptomics analyses found down-regulation in key lipogenic genes (e.g. SCD, ELOVL5) in responders relative to non-responders; metabolomics showed increase in ketone bodies; while proteomics revealed differences in lipoproteins. Findings were consistent between genders; with women displaying smaller improvements owing to a better baseline metabolic condition. Integrative analyses identified a plasma omics model that was able to predict non-responders with strong performance (on a testing dataset, the Receiving Operating Curve Area Under the Curve (ROC AUC) was 75% with 95% Confidence Intervals (CI) [67%, 83%]). This model was based on baseline parameters without the need for intrusive measurements and outperformed clinical models (p = 0.00075, with a +14% difference on the ROC AUCs). Our approach document differences between responders and non-responders, with strong contributions from liver and adipose tissues. Differences may be due to de novo lipogenesis, keto-metabolism and lipoprotein metabolism. These findings are useful for clinical practice to better characterize non-responders both prior and during weight loss.

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“…Decreased long-chain n-3 PUFA was associated with reduced apo CII level in E2 carriers, after FA intervention. These results suggest that subjects with MetS may benefit from personalized dietary interventions based on APOE genotype [26].…”

Section: Candidate Gene Association Studiesmentioning

confidence: 78%

Genetic Diversity of Insulin Resistance and Metabolic Syndrome

Lee¹,

Ahn²,

Park³

et al. 2021

Genetic Variation

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A key in the etiology of a cluster of metabolic syndrome such as hyperglycemia, dyslipidemia, and obesity is known for insulin resistance, which is becoming a major global public health problem. Extensive studies have revealed many genetic factors for both insulin resistance and the components of metabolic syndrome. Advanced modern genotyping methods including genome-wide association studies and next-generation sequencing have allowed for the identification of both common and rare genetic variants related to these chronic disease-associated traits. Multiple genotype–phenotype studies are also needed to identify new and accurate genetic biomarkers in these conditions. The purpose of this chapter is to present genetic variants related to the pathogenesis of metabolic syndrome and insulin resistance and is to review the relevance between insulin resistance and metabolic syndrome clusters in terms of genetic diversity.

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APOE genotype influences insulin resistance, apolipoprotein CII and CIII according to plasma fatty acid profile in the Metabolic Syndrome

Cited by 35 publications

References 62 publications

APOE4 Genotype Exerts Greater Benefit in Lowering Plasma Cholesterol and Apolipoprotein B than Wild Type (E3/E3), after Replacement of Dietary Saturated Fats with Low Glycaemic Index Carbohydrates

APOE4 Genotype Exerts Greater Benefit in Lowering Plasma Cholesterol and Apolipoprotein B than Wild Type (E3/E3), after Replacement of Dietary Saturated Fats with Low Glycaemic Index Carbohydrates

Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics

Genetic Diversity of Insulin Resistance and Metabolic Syndrome

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