Genetic Evidence for a Causal Relationship between Hyperlipidemia and Type 2 Diabetes in Mice.
Genetic Evidence for a Causal Relationship between Hyperlipidemia and Type 2 Diabetes in Mice.
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DOI：
10.3390/ijms23116184
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发表时间：
2022-05-31
影响因子：
5.6
通讯作者：
Shi, Weibin
中科院分区：
文献类型：
--
作者：
Shi, Lisa J.;Tang, Xiwei;He, Jiang;Shi, Weibin
血脂异常被认为是2型糖尿病（T2 D）的一个危险因素，但他汀类药物和候选基因的研究表明，循环脂质可以防止T2 D的发展。Apoe-null（Apoe-/-）小鼠品系发生自发性血脂异常，并表现出对饮食诱导的T2 D的易感性的广泛变化。因此，我们使用Apoe-/-小鼠来阐明循环脂质与T2 D的表型和遗传关系。雄性F2组由LP/J和BALB/cJ Apoe-/-小鼠之间的杂交产生，并饲喂12周的西方饮食。测量空腹、非空腹血糖和血脂水平，并使用miniMUGA阵列进行基因分型。我们在15号染色体上发现了一个靠近60 Mb的主要QTL Nhdlq 18，它影响空腹和非空腹状态下的非HDL胆固醇和甘油三酯水平。该QTL与调节空腹和非空腹血糖水平的QTL Bglu 20一致。F2小鼠血浆非HDL胆固醇和甘油三酯水平与血糖水平密切相关。校正非HDL胆固醇或甘油三酯后，Bglu 20消失。这些结果证明了血脂异常在小鼠T2 D发展中的致病作用。
Dyslipidemia is considered a risk factor for type 2 diabetes (T2D), yet studies with statins and candidate genes suggest that circulating lipids may protect against T2D development. Apoe-null (Apoe-/-) mouse strains develop spontaneous dyslipidemia and exhibit a wide variation in susceptibility to diet-induced T2D. We thus used Apoe-/- mice to elucidate phenotypic and genetic relationships of circulating lipids with T2D. A male F2 cohort was generated from an intercross between LP/J and BALB/cJ Apoe-/- mice and fed 12 weeks of a Western diet. Fasting, non-fasting plasma glucose, and lipid levels were measured and genotyping was performed using miniMUGA arrays. We uncovered a major QTL near 60 Mb on chromosome 15, Nhdlq18, which affected non-HDL cholesterol and triglyceride levels under both fasting and non-fasting states. This QTL was coincident with Bglu20, a QTL that modulates fasting and non-fasting glucose levels. The plasma levels of non-HDL cholesterol and triglycerides were closely correlated with the plasma glucose levels in F2 mice. Bglu20 disappeared after adjustment for non-HDL cholesterol or triglycerides. These results demonstrate a causative role for dyslipidemia in T2D development in mice.
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DOI：
10.1097/med.0000000000000321
发表时间：
2017-04
期刊：
Current opinion in endocrinology, diabetes, and obesity
影响因子：
--
作者：
Attie AD;Churchill GA;Nadeau JH
通讯作者：
Nadeau JH
影响因子：
2.5
作者：
Keirns BH;Sciarrillo CM;Koemel NA;Emerson SR
通讯作者：
Emerson SR
影响因子：
6.5
作者：
Leduc, Magalie S.;Hageman, Rachael S.;Paigen, Beverly
通讯作者：
Paigen, Beverly
高脂血症小鼠高血糖与颈动脉粥样硬化之间的遗传联系。
影响因子：
3.5
作者：
Shi LJ;Chagari B;An A;Chen MH;Bao Y;Shi W
通讯作者：
Shi W
影响因子：
3.3
作者：
Grainger, Andrew T.;Pilar, Nathanael;Shi, Weibin
通讯作者：
Shi, Weibin