期刊
BIOMEDICINES
卷 10, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines10061429
关键词
low-density lipoprotein receptor; apolipoprotein E; hyperglycemia; type 2 diabetes; Western diet
资金
- NIH [R01 DK116768, HL112281]
- Commonwealth Health Research Board (CHRB) Virginia
Comparing C3H-Ldlr(-/-) mice with C3H-Apoe(-/-) mice, we found that a Western diet and hyperlipidemia lead to the development of type 2 diabetes, regardless of genetic causes.
Apoe(-/-) and Ldlr(-/-) mice are two animal models extensively used for atherosclerosis research. We previously reported that Apoe(-/-) mice on certain genetic backgrounds, including C3H/HeJ (C3H), develop type 2 diabetes when fed a Western diet. We sought to characterize diabetes-related traits in C3H-Ldlr(-/-) mice through comparing with C3H-Apoe(-/-) mice. On a chow diet, Ldlr(-/-) mice had lower plasma total and non-HDL cholesterol levels but higher HDL levels than Apoe(-/-) mice. Fasting plasma glucose was much lower in Ldlr(-/-) than Apoe(-/-) mice (male: 122.5 +/- 5.9 vs. 229.4 +/- 17.5 mg/dL; female: 144.1 +/- 12.4 vs. 232.7 +/- 6.4 mg /dL). When fed a Western diet, Ldlr(-/-) and Apoe(-/-) mice developed severe hypercholesterolemia and also hyperglycemia with fasting plasma glucose levels exceeding 250 mg/dL. Both knockouts had similar non-HDL cholesterol and triglyceride levels, and their fasting glucose levels were also similar. Male Ldlr(-/-) mice exhibited greater glucose tolerance and insulin sensitivity compared to their Apoe(-/-) counterpart. Female mice showed similar glucose tolerance and insulin sensitivity though Ldlr(-/-) mice had higher non-fasting glucose levels. Male Ldlr(-/-) and Apoe(-/-) mice developed moderate obesity on the Western diet, but female mice did not. These results indicate that the Western diet and ensuing hyperlipidemia lead to the development of type 2 diabetes, irrespective of underlying genetic causes.
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