Conjugated linoleic acid isomers induced dyslipidemia and lipoatrophy are exacerbated by rosiglitazone in ApoE null mice fed a Western diet

Abstract

BACKGROUND: Insulin sensitizers have been used to treat Type 2 diabetes. However, their non-negligible side effects have led to cardiovascular concerns and the withdrawal of a member, rosiglitazone. OBJECTIVE: We combined conjugated linoleic acid (CLA) with rosiglitazone to test for amelioration of side effects posed by rosiglitazone in vivo. METHODS: We utilized ApoE null mice fed with Western diet (WD) to test our hypothesis. Mice were fed WD, with or without CLA administration, for 12 weeks. CLA utilized in our study consisted of a 1:1 ratio of 95% pure c9,t11, and t10,c12 isomers at a concentration of 0.1% w/v in fat-free milk. Starting from Week 12, select mice received rosiglitazone. RESULTS: It was found that mice receiving CLA from Week 0 and rosiglitazone from Week 12 had the lowest body weight and exacerbated hepatomegaly. Although these mice had attenuated insulin resistance compared to mice receiving only Western diet, they display a marked increase in total plasma cholesterol and low-density lipoprotein (LDL) cholesterol. Mice receiving early CLA administration developed hyperleptinemia, which was not restored by rosiglitazone. CONCLUSION: Taken together, against the background of ApoE null genotype and WD feeding, simultaneous administration of 1:1 CLA and rosiglitazone led to dyslipidemic lipoatrophy.