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

Abstract

Citation: Meadus WJ, Vahmani P, Duff P, Zantinge JL, Turner TD, and Dugan M.E.R. Oxidation and apoptosis are induced by CLA-t10c12 similar to DHA in 3T3 adipocyte cells. Functional Foods in Health and Disease 2017; 7(2): 149-167 ABSTRACT Background: Commercial conjugated linoleic acid (CLA) dietary supplements contain an equal mixture of the C18:2 isomers, cis-9trans-11 and trans-10cis-12. Predominantly, CLAc9t11 occurs naturally in meat and dairy products at ~ 0.5% of total fat , whereas CLAt10c12 occurs at > 0.1%. Recent studies show that CLA-c9t11 generally promotes lipid accumulation but CLA-t10c12 may inhibit lipid accumulation and may also promote inflammation. The omega-3 fatty acids α-linolenic acid (C18:3n-3) and docosahexaenoic acid (DHA) have also been observed to inhibit lipid accumulation and effect inflammation; therefore we examined the effects of the two main isomers of CLA and omega -3 fatty acids C18:3n-3 and DHA at the molecular level to determine if they are causing similar oxidative stresses.Methods: Purified CLA-c9t11 and CLA-t10c12 were added to 3T3 cells induced into mature adipocyte cultures at 100uM concentrations and compared with 100uM C18:3n-3 (α-linolenic acid) and 50uM docosahexaenoic acid (DHA) to observe their effect on growth, gene transcription and general oxidation. The results of multiple separate trials were averaged and compared for significance at levels of P < 0.05, using one way ANOVA and Student's t-test.Results: C18:3n-3, DHA and CLA-t10c12 inhibited 3T3 adipose cell growth and caused a significant increase in lipid hydro peroxide activity. CLA-t10c12 and c9t11 increased AFABP, FAS and ACOX1 mRNA gene expression but DHA and C18:3n-3 decreased the same mRNAs. CLA-c9t11 but not the t10c12 stimulated adipoQ expression even though; CLA-c9t11 had only a slightly greater affinity for PPARγ than CLA-t10c12, according to TR-FRET assays. 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, C18:3n-3 and CLA-t10c12 but not CLA-c9t11. This correlated with an increase in apoptosis factors, caspase 3, Bcl-2 and BAXs. Apoptosis factors were partially reduced by co-treatment with lipophilic anti-oxidant α-tocopherol.Conclusions: CLA-t10c12 stimulated the production of more reactive oxygen species (ROS) than CLA-c9t11. In response, cascades of genes are activated in detoxification, inflammation or apoptosis, to deal with the potentially damaging effects of ROS including CCL5 and MCP-1. This was similar to treatment with the omega-3 fatty acids but the fat metabolic enzymes were generally inhibited by C18:3n-3 and DHA except CLA-t10c12 which did not stimulate adipoQ.

The antioxidant components of milk and their role in processing, ripening, and storage: Functional food

“…Several vegetable oils have LA enhancing property in milk. Rumen biohydrogenation can be prevented by addition of oilseeds; hence, inclusion of oilseeds in the diet has been explored in many studies [ 35 ]. Many trials established that a high level of unsaturated fatty acid (UFA) in milk, particularly polyunsaturated fatty acids (PUFAs), increases the risk of oxidation and off-flavor [ 36 ].…”