Novel anti‐adipogenic properties of the individual trans8,cis10 conjugated linoleic acid (CLA) isomer in 3T3‐L1 adipocytes

Abstract

In this study, we hypothesized that trans(t)8,cis(c)10 conjugated linoleic acid (CLA) isomer possesses anti-adipogenic properties in resemblance to its structural analog, the t10,c12 CLA isomer. After chemical synthesis and purification of the t8,c10 CLA isomer in our laboratory, we report, for the first time, its individual action on the lipid metabolism of 3T3-L1 adipocytes. Cells were supplemented with 50 mM of linoleic acid (LA), t10,c12, or t8,c10 during 11 days of differentiation. Intracellular triacylglycerols (TAG) content was affected by fatty acid treatments. The t8,c10 CLA isomer reduced TAG content but in a lower magnitude, three times less, than the t10,c12 isomer. The supplementation with LA increased TAG storage thus reversing CLA isomers effect. The fatty acid profile of treated adipocytes showed that the t8,c10 CLA isomer incorporation was identical to the t10,c12. The mRNA expression of several genes involved in lipogenesis, lipolysis, fatty acid b-oxidation, and adipocytes differentiation underlying anti-adipogenic action was determined. The t10,c12 CLA isomer decreased gene expression levels related to lipogenesis but did not up-regulate HSL and PPARA associated with lipolysis and fatty acid b-oxidation, respectively. The t8,c10 CLA isomer increased SCD mRNA level without affecting delta 9 desaturase index-16, an indicator of SCD enzyme activity. Taken together, our results indicate that the t8,c10 CLA isomer, tested individually on lipid metabolism of 3T3-L1 adipocytes, is anti-adipogenic.Practical applications: New and more effective weight loss supplements are widely pursued facing the worldwide obesity epidemic. Over the last few decades, the anti-adipogenic properties of conjugated linoleic acid (CLA) have been studied and confirmed for the t10,c12 CLA isomer but, until now, there was no information on its structural analog, the t8,c10. This study provides novel insights on the putative anti-adipogenic ability of the t8,c10 CLA isomer exploiting potential molecular mechanisms of action in 3T3-L1 adipocytes.

Trans10,cis15 18:2 Isolated from Beef Fat Does Not Have the Same Anti‐Adipogenic Properties as Trans10,cis12–18:2 in 3T3‐L1 Adipocytes

“…Interestingly, we found 15:0 was the second major saturated fatty acid in adipocytes following 16:0. The presence of 15:0 and its delta-9 desaturation product (c9-15:1) has been previously reported in 3T3-L1 adipocytes [24,28]. It has been shown that 15:0 mainly originates from alpha oxidation of 16:0 and can subsequently undergo delta-9 desaturation [28,29].…”

“…In contrast to t10,c12-18:2, supplementation with t10,c15 or LNA did not affect adipocyte TAG or total fatty acids. Recently, Martins et al [24] showed that treating 3T3-L1 adipocytes with t8,c10-18:2 (a CLA isomer) reduced the TAG content of cells, although to a much smaller extent than t10,c12-18:2 (−20 % vs. −80 %). These findings combined with our data suggest that the trans double bond at carbon 10 in conjunction with a cis double bond at carbon 12 is required for the anti-adipogenic activity of t10,c12-18:2.…”

PPAR‐γ: Its ligand and its regulation by microRNAs

“…In inflammatory bowel disease, Susana et al have shown that treatment with CLA ( trans ‐10, cis ‐12) restrains adipogenesis by downregulating PPAR‐γ . Similarly, ( trans ‐8, cis‐ 10) isomer of CLA can act as antiadipogenic in 3T3‐L1 adipocytes . Furthermore, synchronized functions between SIRT1 and AMPK that are used by ( trans ‐10, cis ‐12) of CLA can hinder PPAR‐γ expression in 3T3‐L1 adipocytes for lowering TG levels .…”

“…41 Similarly, (trans-8, cis-10) isomer of CLA can act as antiadipogenic in 3T3-L1 adipocytes. 42 Furthermore, synchronized functions between SIRT1 and AMPK that are used by (trans-10, cis-12) of CLA can hinder PPAR-γ expression in 3T3-L1 adipocytes for lowering TG levels. 43 Another CLA isomer, punicic acid (PA), found in pomegranate seeds, has been discovered to be antidiabetic, antiobesity, and anticarcinogenic.…”