Investigating the isomer-specific effects of conjugated linoleic acid on adiposity and insulin resistance in db/db mice.

摘要

Conjugated linoleic acid (CLA) has been shown to reduce adiposity in humans and in some animal models. Trans (t)-10, cis (c)-12 CLA can lead to severe fat ablation and worsen insulin resistance in lean and ob/ob mice as opposed to improving insulin sensitivity without changes in adiposity in fa/fa Zucker rats. In order to investigate whether this is a species or genotype specific effect, seven-week old db/db mice were randomly assigned to groups fed ad libitum either 0.4% c9, t 11 CLA, 0.4% t10, c12 CLA or a control diet for six weeks. A weight-matched group were fed restricted amounts of a control diet to match the body weight of the t10, c12 CLA fed mice. Serum glucose, insulin, triglycerides and leptin concentrations were assayed and protein levels of select insulin signalling mediators and leptin in the epididymal adipose tissue were analyzed by Western blotting.;Protein kinase C (PKC) describes a group of enzymes that have gained much attention for their ability to phosphorylate cell surface receptors and insulin signalling mediators thereby altering normal insulin signalling. To investigate possible mechanisms for the action of CLA on insulin signalling, the levels of the protein kinase C (PKC) isoforms from all classes (conventional, novel and atypical) were quantified in the epididymal adipose tissue of the mice as well as in mature 3T3-L1 adipocytes treated with CLA. PKCalpha, betaI, theta, epsilon, mu and zeta/lambdaA were all found at varying levels and subcellular locations in the epididymal adipose tissue of lean and db/db mice and 3T3-Ll adipocytes.;These results demonstrate that the t10, c12 isomer of CLA depletes adipose tissue of db/db mice without worsening insulin sensitivity while influencing the activity of a variety of PKC isoforms in adipose tissue. This is one of the first studies to determine the presence of these enzymes in the adipose tissue of db/db mice and their ability to be modulated by CLA.;Mice fed t10, c12 CLA ceased to gain weight while simultaneously increasing their feed intake. HOMA-IR revealed no differences in insulin resistance among any of the db/db mice. Levels of the phosphorylated p85 subunit of phosphatidylinositol 3-kinase were highly elevated in epididymal fat of db/db mice and were highest in the t10, c12 CLA fed group. Serum leptin concentrations of c9, t11 CLA fed mice were higher than both control and t10, c12 CLA fed mice. However, the t10, c12 CLA-fed mice had the greatest concentration of leptin when expressed per mass of visceral adipose tissue. Elevated leptin protein levels were also seen in epididymal adipose tissue of the t10, c12 CLA fed mice.