CLA isomer t10,c12 induce oxidation and apoptosis in 3t3 adipocyte cells in a similar effect as omega-3 linolenic acid and DHA.

Jon Meadus, P. Vahmani, P. Duff, J.L. Zantinge, T.D. Turner, M.E.R. Dugan

Abstract


Background: Commercial conjugated linoleic acid (CLA) dietary supplements of contain an equal mixture of the C18:2 isomers, cis-9,trans-11 and trans-10,cis-12. CLA-c9t11 occurs naturally in meat and dairy products as the dominant CLA at 75%, whereas the CLA-t10c12 occurs at <1%. CLA-c9t11 generally promotes lipid accumulation but CLA-t10c12 inhibits lipid accumulation and may promote inflammation.

Methods: Purified CLA-c9t11 and CLA-t10c12 were added to 3T3 mature adipocyte cultures at 100uM concentrations and compared with 100uM C18:3(n-3) (α-linolenic acid) and 50uM docosahexaenoic acid (DHA) to study their effect on growth, gene transcription and general oxidation. The results of 4 separate trials were averaged and compared for significance using one way ANOVA and Student’s t-test.

Results: C18:3(n-3), DHA and CLA-t10c12 were inhibitory to 3t3 adipose cell growth and caused significant lipid hydro peroxide activity. CLA-t10c12 and c9t11 increased AFABP, FAS and ACOX1 mRNA expression but DHA and C18:3(n-3) decreased the same mRNAs. CLA-c9t11 but not the t10c12 stimulated adipoQ expression even though; c9t11 had only a slightly greater affinity for PPARγ than CLA- t10c12. The expression of the xenobiotic metabolism genes, aldo-keto reductase 1c1  (akr1c1), superoxide dismutase (SOD) and inflammation chemokine secretions of  eotaxin (CCL11), Rantes (CCL5), MIG (CCL9) and MCP-1 were increased by DHA, C18:3(n-3) and CLA-t10c12. This correlated with apoptosis factors, caspase 3, Bcl-2 and BAXs which were partially reduced by co-treatment with lipophilic anti-oxidant α-tocopherol.

Conclusions: Based on this evidence, CLA-t10c12 promoted more reactive oxygen species (ROS) than CLAc9t11, in a similar effect as C18:3(n-3) and DHA. In response, cascades of genes are activated to deal with the potentially damaging effects of ROS through detoxification, inflammation or apoptosis.

Keywords: CLA-t10c12, CLA-c9t11, gene expression, adipocyte lipid hydroperoxide, DHA,3T3 adipocytes, apoptosis.


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