Ldlr-Deficient Mice with an Atherosclerosis-Resistant Background Develop Severe Hyperglycemia and Type 2 Diabetes on a Western-Type Diet.

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.

• Authors: Weibin Shi, Jing Li, Kelly Bao, Mei-Hua Chen, Zhenqi Liu
• Journal: Biomedicines (Biomedicines) Vol. 10 Issue 6 (Jun 16 2022) ISSN: 2227-9059 [Print] Switzerland
• PMID: 35740449 (Publication Type: Journal Article)