The effects of the conjugated linoleic acid (CLA) isomers c9, t11 CLA and t10,c12 CLA on peroxisome proliferator activated receptor gamma (PPARy) gene expression in a monocytic cell line
Al-Nakhaili, Mohammed Khalifa
Cardiff Metropolitan University
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Type 2 Diabetes mellitus (T2DM) is a metabolic disorder that presents itself mainly in elderly people and develops due to either insufficient insulin production or insulin resistance by body cells. Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome proliferator-activated receptor gamma (PPARy), which are currently used in the treatment of T2DM, However, the treatment with TZDs has some limitations and can cause some side effects including fluid retention peripheral edema mild anaemia, weight gain and possible increased risk of congestive heart failure. Conjugated linoleic acid (CLA) is a fatty acid that belongs to the polyunsaturated fatty acids group in which cis-9, trans-LL CLA and trans-10, cis-12 CLA are the predominant isomers and being the primary focus of most of the studies evaluating the biological activities of CLA. CLA is a natural PPARy ligand found to promote many physiological effects including lipid and glucose metabolism and to increase insulin sensitivity. This study examined the role of CLA isomers (cis-9,trans-ll CLA and trans-l0,cis-12 CLA) in different concentrations (l00uM md 20uM) on PPARy gene expression by using human monocytic leukaemia cell line THP-1 at various time points (0, 6, 24, 48, and 72 hours). RNA was extracted from THP-1 cells and amplified by Real time (RT-PCR) to measure and display PPARy gene expression relative to the housekeeping gene GAPDH. This study has demonstrated that conjugated linoleic acid isomers tl0,c12 CLA and c9,tll CLA are capable of increasing PPARy gene expression in THP-1 cells in majority of the time points (P-value is <0.05). This may contribute to the critical role in the regulation of insulin sensitivity and in reducing blood glucose in T2DM patients. Additionally, this study has generated important insights into the ability of CLA and especially tl0,cl2 to activate PPARy, which is associated with the use of TZDs in diabetes treatments. Therefore, the use of CLA could have a potential nonpharmacological role for the prevention and treatment of T2DM. However, the positive health effects attributed to CLA are mainly based on cell culture models and animal studies with comparatively less scientific evidence from direct studies on humans. Therefore, further studies will be undertaken to clarify the molecular mechanism underlying CLA effects in health benefits, especially antidiabetagenic, and any possible negative effects.
MSc Biomedical Sciences
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