Genetic Evidence for a Causal Relationship between Hyperlipidemia and Type 2 Diabetes in Mice

Shi, Lisa J.; Tang, Xiwei; He, Jiang; Shi, Weibin

doi:10.3390/ijms23116184

Cited by 2 publications

(2 citation statements)

References 67 publications

(79 reference statements)

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“…Interval mapping plots for Chr15 show the coincidence of the proximal atherosclerosis QTL ( Ath52 ) with QTL for fasting, non-fasting plasma glucose ( Bglu20 ), LDL cholesterol and triglyceride levels ( Nhdlq18 ) ( Figure 3 A–G). Details on Bglu20 and Nhdlq18 and the characterization of plasma lipids and glucose in the F2 mice have been reported [ 16 , 39 ]. The LP allele was associated with larger atherosclerotic lesion size and higher plasma levels of glucose, non-HDL cholesterol and triglyceride, while the BALB allele had opposite effects on these traits ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic Mice

Abramson

Shi

Lee

et al. 2022

Cells

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Hyperlipidemia and type 2 diabetes (T2D) are major risk factors for atherosclerosis. Apoe-deficient (Apoe−/−) mice on certain genetic backgrounds develop hyperlipidemia, atherosclerosis, and T2D when fed a Western diet. Here, we sought to dissect phenotypic and genetic relationships of blood lipids and glucose with atherosclerotic plaque formation when the vasculature is exposed to high levels of cholesterol and glucose. Male F2 mice were generated from LP/J and BALB/cJ Apoe−/− mice and fed a Western diet for 12 weeks. Three significant QTL Ath51, Ath52 and Ath53 on chromosomes (Chr) 3 and 15 were mapped for atherosclerotic lesions. Ath52 on proximal Chr15 overlapped with QTL for plasma glucose, non-HDL cholesterol, and triglyceride. Atherosclerotic lesion sizes showed significant correlations with fasting, non-fasting glucose, non-fasting triglyceride, and body weight but no correlation with HDL, non-HDL cholesterol, and fasting triglyceride levels. Ath52 for atherosclerosis was down-graded from significant to suggestive level after adjustment for fasting, non-fasting glucose, and non-fasting triglyceride but minimally affected by HDL, non-HDL cholesterol, and fasting triglyceride. Adjustment for body weight suppressed Ath52 but elevated Ath53 on distal Chr15. These results demonstrate phenotypic and genetic connections of blood glucose and triglyceride with atherosclerosis, and suggest a more prominent role for blood glucose than cholesterol in atherosclerotic plaque formation of hyperlipidemic mice.

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Section: Resultsmentioning

confidence: 99%

Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic Mice

Abramson

Shi

Lee

et al. 2022

Cells

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“…In animal experiments, ApoE4 mice showed impaired glucose and insulin tolerance, reduced insulin secretion, and decreased cognitive and sensorimotor characteristics compared to ApoE3 mice, and these changes were associated with central nervous system processes. 47 Dyslipidemia is considered to be a risk factor for diabetes, 48 so the regulatory effects of ApoE expressed by different APOE genotypes on lipid metabolism are different, which is related to the pathogenesis of diabetes. The mechanism of the relationship between ApoE subtypes and DM risk is unclear and needs more in-depth research to reveal.…”

Section: Discussionmentioning

confidence: 99%

E2/E3 and E3/E4 Genotypes of the Apolipoprotein E are Associated with Higher Risk of Diabetes Mellitus in Patients with Hypertension

Han,

Xiong,

Zhong

et al. 2023

IJGM

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Objective Apolipoprotein E (APOE) plays an important role in the lipid metabolism. APOE polymorphisms have been implicated in susceptibility to diabetes mellitus (DM). However, the association between APOE polymorphisms and the risk of DM among the hypertensive patients remains unclear. Our study aimed to evaluate this relationship to provide clues for further developing DM in hypertensive patients. Methods The study included 808 hypertensive patients with DM and 1226 hypertensive patients without DM as controls. The APOE 388T>C (rs429358) and 526C>T (rs7412) polymorphisms were genotyped by polymerase chain reaction (PCR) - microarray. Differences in APOE genotypes between subjects and controls were compared. To analyze the relationship between APOE genotypes and DM risk, multiple logistic regression analysis was performed after adjusting for gender, age, smoking history, and drinking history. Results The APOE E2/E4, E3/E3 genotype and ε2, ε3 allele frequency had significant difference between DM patients and controls ( P <0.05). The DM patients with ɛ4 allele had lower level in high-density lipoprotein cholesterol (HDL-C) and higher level in apolipoprotein B (ApoB) than those with ɛ2 allele. The results of logistic regression analysis indicated that the APOE genotype of E2/E3 with adjusted OR=1.350 (95% Cl=1.009–1.806, P =0.043) and E3/E4 with adjusted OR=1.325 (95% Cl=1.034–1699, P =0.026) may be independent risk factors for DM. Conclusion APOE E2/E3 and E3/E4 genotypes may be risk factors for developing diabetes mellitus in hypertensive patients.

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Genetic Evidence for a Causal Relationship between Hyperlipidemia and Type 2 Diabetes in Mice

Cited by 2 publications

References 67 publications

Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic Mice

Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic Mice

E2/E3 and E3/E4 Genotypes of the Apolipoprotein E are Associated with Higher Risk of Diabetes Mellitus in Patients with Hypertension

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