Ldlr-Deficient Mice with an Atherosclerosis-Resistant Background Develop Severe Hyperglycemia and Type 2 Diabetes on a Western-Type Diet
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-Ld...
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| Published in | Biomedicines Vol. 10; no. 6; p. 1429 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
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MDPI AG
16.06.2022
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| Online Access | Get full text |
| ISSN | 2227-9059 2227-9059 |
| DOI | 10.3390/biomedicines10061429 |
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| Abstract | 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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| AbstractList | 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. and mice are two animal models extensively used for atherosclerosis research. We previously reported that 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- mice through comparing with C3H- mice. On a chow diet, mice had lower plasma total and non-HDL cholesterol levels but higher HDL levels than mice. Fasting plasma glucose was much lower in than 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, and 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 mice exhibited greater glucose tolerance and insulin sensitivity compared to their counterpart. Female mice showed similar glucose tolerance and insulin sensitivity though mice had higher non-fasting glucose levels. Male and 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. 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.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. |
| Author | Chen, Mei-Hua Liu, Zhenqi Shi, Weibin Li, Jing Bao, Kelly |
| AuthorAffiliation | 2 Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA; zl3e@hscmail.mcc.virginia.edu 1 Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USA; jjeileen2006@hotmail.com (J.L.); kqb2j@virginia.edu (K.B.); mc2xc@hscmail.mcc.virginia.edu (M.-H.C.) |
| AuthorAffiliation_xml | – name: 1 Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USA; jjeileen2006@hotmail.com (J.L.); kqb2j@virginia.edu (K.B.); mc2xc@hscmail.mcc.virginia.edu (M.-H.C.) – name: 2 Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA; zl3e@hscmail.mcc.virginia.edu |
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| SubjectTerms | Animal models Apolipoprotein E Arteriosclerosis Atherosclerosis Cardiovascular disease Cholesterol Diabetes Diabetes mellitus (non-insulin dependent) Diet Fasting Females Glucose Glucose tolerance High density lipoprotein Hypercholesterolemia Hyperglycemia Hyperlipidemia Insulin Laboratories Lipids Low density lipoprotein low-density lipoprotein receptor Males Mutation Plasma Reagents type 2 diabetes Variance analysis Western diet |
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| Title | Ldlr-Deficient Mice with an Atherosclerosis-Resistant Background Develop Severe Hyperglycemia and Type 2 Diabetes on a Western-Type Diet |
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