Abstract
Trans-10,cis-12 conjugated linoleic acid (CLA) has previously been shown to be the CLA isomer responsible for CLA-induced reductions in body fat in animal models, and we have shown that this isomer, but not the cis-9,trans-11 CLA isomer, specifically decreased triglyceride (TG) accumulation in primary human adipocytes in vitro. Here we investigated the mechanism behind the isomer-specific, CLA-mediated reduction in TG accumulation in differentiating human preadipocytes. Trans-10,cis-12 CLA decreased insulin-stimulated glucose uptake and oxidation, and reduced insulin-dependent glucose transporter 4 gene expression. Furthermore, trans-10,cis-12 CLA reduced oleic acid uptake and oxidation when compared with all other treatments. In parallel to CLA's effects on metabolism, trans-10,cis-12 CLA decreased, whereas cis-9,trans-11 CLA increased, the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and several of its downstream target genes when compared with vehicle controls. Transient transfections demonstrated that both CLA isomers antagonized ligand-dependent activation of PPARgamma. Collectively, trans-10,cis-12, but not cis-9, trans-11, CLA decreased glucose and lipid uptake and oxidation and preadipocyte differentiation by altering preadipocyte gene transcription in a manner that appeared to be due, in part, to decreased PPARgamma expression.
Highlights
Trans-10,cis-12 conjugated linoleic acid (CLA) has previously been shown to be the CLA isomer responsible for CLA-induced reductions in body fat in animal models, and we have shown that this isomer, but not the cis-9,trans-11 CLA isomer, decreased triglyceride (TG) accumulation in primary human adiopcytes in vitro
The monounsaturated fatty acid (MUFA)/saturated fatty acid (SFA) ratio was lower in cultures treated with 30 M trans-10,cis-12 CLA compared with vehicle controls
In keeping with these data, the mRNA level of stearoyl-CoA desaturase-1 (SCD-1), an enzyme that introduces a double bond at position ⌬9 in 16:0 and 18:0, was greatly reduced in cultures treated with 30 M trans-10,cis-12 CLA when compared with cultures treated with cis-9,trans-11 CLA or vehicle (Fig. 2)
Summary
Trans-10,cis-12 conjugated linoleic acid (CLA) has previously been shown to be the CLA isomer responsible for CLA-induced reductions in body fat in animal models, and we have shown that this isomer, but not the cis-9,trans-11 CLA isomer, decreased triglyceride (TG) accumulation in primary human adiopcytes in vitro. Satory and Smith [19] found paradoxically that postconfluent cultures of differentiating 3T3-L1 preadipocytes treated with a crude mixture of CLA isomers had greater rates of lipogenesis and increased levels of TG compared with vehicle controls, yet CLA inhibited proliferation in preconfluent cultures. This CLA-mediated inhibition of proliferation was confirmed by Brodie et al [20], yet they found that a crude mixture of CLA isomers decreased TG content and/or markers of adipocyte differentiation in 3T3-L1 preadipocytes.
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