Trans-10,cis-12 Conjugated Linoleic Acid Suppresses the Desaturation of Linoleic and α-Linolenic Acids in HepG2 Cells

Abstract

The objective of this study was to determine the effects of cis-9,trans-11 and trans-10,cis-12 CLA on the fatty acid desaturation in a human hepatoma cell line, HepG2. Therefore, experiments were conducted in which HepG2 cells were incubated with various concentrations of those fatty acids and the concentrations of fatty acids in various lipid fractions of HepG2 cells were determined. In the presence of linoleic acid as substrate, cells treated with 25 micromol/L of trans-10,cis-12 CLA had lower ratios of dihomo-gamma-linoleic acid to linoleic acid and of arachidonic acid to linoleic acid in phospholipids than control cells; with alpha-linolenic acid as substrate, they had a lower ratio of eicosapentaenoic acid to alpha-linolenic acid in phospholipids than control cells. Cells treated with cis-9,trans-11 CLA did not differ in these ratios from control cells. Cells treated with trans-10,cis-12 CLA had also a markedly lower ratio of monounsaturated fatty acids (MUFA) to saturated fatty acids (SFA) in lipids than control cells; cells treated with cis-9,trans-11 CLA had a slightly lower MUFA:SFA ratio than control cells. These findings suggest that trans-10,cis-12 CLA suppresses Delta9-, Delta6- and Delta5-desaturation in HepG2 cells; cis-9,trans-11 CLA slightly reduces Delta9-desaturation but does not inhibit Delta6- and Delta5-desaturation. Moreover, HepG2 cells treated with 100 micromol/L of trans-10,cis-12 CLA released larger amounts of 6-keto-prostaglandin F(1alpha) and prostaglandin F(2alpha) than control cells. Treatment of cells with cis-9,trans-11 CLA did not alter the release of these eicosanoids compared with control cells. In conclusion, this study suggests that trans-10,cis-12 CLA has significant effects on the metabolism of essential fatty acids in HepG2 cells, whereas cis-9, trans-11 CLA does not have any effect in this respect.

Influence of dietary conjugated linoleic acid (CLA) on lipid and fatty acid composition in liver and flesh of Atlantic salmon (Salmo salar)

“…In mammals, CLA is also known to decrease the activity and gene expression of SCD and may also suppress Δ6 and Δ5 desaturases, and elongase (Choi et al, 2001(Choi et al, , 2002Chuang et al, 2001a,b;Eder et al, 2002 have some similar effects in salmon. Thus, there was an indication that SCD in liver was reduced as evidenced by increased 18:0 and decreased 18:1n-9, and a similar effect was observed previously in salmon fry fed CLA (Berge et al, 2004).…”

“…Decreased body fat has also been observed in human studies (Smedman and Vessby, 2001;Thom et al, 2001;Riserus et al, 2001) although the effect was much less than that observed with mice (Terpstra, 2004). CLA is also known to decrease the activity and gene expression of mammalian stearoyl CoA Δ9 desaturase (SCD) (Choi et al, 2001(Choi et al, , 2002 and may also suppress Δ6 and Δ5 desaturase (Chuang et al, 2001a;Eder et al, 2002) and elongase (Chuang et al, 2001b). Further studies have suggested that CLA may enhance growth and feed efficiency in young rodents ) although this has not been consistently observed.…”

Isomer-specific regulation of metabolism and PPARγ signaling by CLA in human preadipocytes

“…For example, the trans-10,cis-12 isomer of CLA has been shown to inhibit fatty acid desaturation by decreasing the activity or mRNA levels of Δ9-, Δ6-, and Δ5-desaturases in murine preadipocytes or hepatic microsomes, human breast cancer cells, and human hepatocytes (21)(22)(23)(24)(25). This trans-10,cis-12 CLA-mediated reduction in fatty acid desaturation results in a decreased monounsaturated fatty acid (MUFA) to saturated fatty acid (SFA) ratio (21,23). It has been postulated that without adequate levels of the MUFA oleate, a preferential substrate for TG synthesis (26), TG levels are diminished.…”

Incorporation of cis-9,trans-11 or trans-10,cis-12 conjugated linoleic acid into plasma and cellular lipids in healthy men

“…Thus, the dose of individual isomers may be relatively low despite high intakes of total CLA compared with the basal diet. Because some effects of CLA may be isomerspecific (11,12,(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), differences in the intake of bioAbbreviations: CE, cholesteryl ester; CLA, conjugated linoleic acid; FAME, fatty acid methyl ester; NEFA, nonesterified fatty acid; PBMC, peripheral blood mononuclear cell; PC, phosphatidylcholine. …”