Affiliations: [a] Division of Biomedical Sciences, Faculty of Science, University of Nottingham Malaysia Campus, Jalan Broga, Semenyih, Selangor Darul Ehsan, Malaysia
| [b] Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| [c] Present address: Biomedical Translation Research Centre, National Biotechnology Research Park, No 99, Lane 130, Academia Road Section 1, Nangang District, Taipei City 11571, Taiwan
| [d] Present address: Swansea University Medical School, Singleton Park, Swansea SA2 8PP, Wales, United Kingdom
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.
