Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse

Abstract

Conjugated linoleic acids (CLA) are a class of positional, geometric, conjugated dienoic isomers of linoleic acid (LA). Dietary CLA supplementation results in a dramatic decrease in body fat mass in mice, but also causes considerable liver steatosis. However, little is known of the molecular mechanisms leading to hepatomegaly. Although c9,t11 -and t10,c12 -CLA isomers are found in similar proportions in commercial preparations, the respective roles of these two molecules in liver enlargement has not been studied. We show here that mice fed a diet enriched in t10,c12 -CLA (0.4% w/w) for 4 weeks developed lipoatrophy, hyperinsulinemia, and fatty liver, whereas diets enriched in c9,t11 -CLA and LA had no significant effect. In the liver, dietary t10,c12 -CLA triggered the ectopic production of peroxisome proliferator-activated receptor ␥ (PPAR ␥ ), adipocyte lipid-binding protein and fatty acid transporter mRNAs and induced expression of the sterol responsive element-binding protein-1a and fatty acid synthase genes. In vitro transactivation assays demonstrated that t10,c12 -and c9,t11 -CLA were equally efficient at activating PPAR ␣ , ␤ / ␦ , and ␥ and inhibiting liver-X-receptor.Thus, the specific effect of t10,c12 -CLA is unlikely to result from direct interaction with these nuclear receptors. Instead, t10,c12 -CLA-induced hyperinsulinemia may trigger liver steatosis, by inducing both fatty acid uptake and lipogenesis. -Clément, L., H. Poirier, I. Niot, V. Bocher, M. Guerre-Millo, S. Krief, B. Staels, and P. Besnard. Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse.

Conjugated linoleic acid and obesity control: efficacy and mechanisms

“…15 Similar results have been obtained in other studies in mice. 98,99 The tissue examination did not show any severe pathological changes but increased lipid droplets in the liver and spleen. 15,20 The biochemical, cellular and molecular mechanisms involved in the development of fatty liver and spleen are not well established.…”

The effect of trans-10,cis-12 conjugated linoleic acid on lipogenesis is tissue dependent in hamsters

“…In contrast, Azain et al [4] did not find changes in FAS activity induced by CLA feeding in rats. Other authors found reduced expression of FAS and ACC in mice [5,6] . In the present work, trans-10,cis-12 CLA feeding significantly reduced the mRNA expression of the two specific lipogenic enzymes measured (ACC, FAS).…”

Non-fat milk solids attenuate hypercholesterolemic effect of conjugated linoleic acid

“…One of the mechanisms behind an increase in liver lipids may involve the reduction of leptin and adiponectin mRNA by t10, c12-CLA (Warren et al 2003). Also, the accumulation of fat in liver may be due to the hyperinsulinemia caused by CLA (Clément et al 2002) which SMP could not prevent as milk proteins are also insulinotropic (Nilsson et al 2004). Insulin activates fatty acid uptake in the liver possibly causing high fat deposition in liver of CLA and CLA + SMP groups.…”