| First Author | Shi LJ | Year | 2022 |
| Journal | Int J Mol Sci | Volume | 23 |
| Issue | 11 | PubMed ID | 35682864 |
| Mgi Jnum | J:326023 | Mgi Id | MGI:7287030 |
| Doi | 10.3390/ijms23116184 | Citation | Shi LJ, et al. (2022) Genetic Evidence for a Causal Relationship between Hyperlipidemia and Type 2 Diabetes in Mice. Int J Mol Sci 23(11) |
| abstractText | 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. |
