Abstract

BackgroundStudies in rodents and some studies in humans have shown that conjugated linoleic acid (CLA), especially its trans-10, cis-12 isomer, reduces body fat content. However, some but not all studies in mice and humans (though none in rats) have found that CLA promotes insulin resistance. The molecular mechanisms responsible for these effects are unclear, and there are conflicting reports on the effects of CLA on peroxisomal proliferator-activated receptor-γ (PPARγ) activation and expression. We have conducted three experiments with CLA in obese mice over three weeks, and one over eleven weeks. We have also investigated the effects of CLA isomers in PPARγ and PPARα reporter gene assays.ResultsInclusion of CLA or CLA enriched with its trans-10, cis-12 isomer in the diet of female genetically obese (lepob/lepob) mice for up to eleven weeks reduced body weight gain and white fat pad weight. After two weeks, in contrast to beneficial effects obtained with the PPARγ agonist rosiglitazone, CLA or CLA enriched with its trans-10, cis-12 isomer raised fasting blood glucose and plasma insulin concentrations, and exacerbated glucose tolerance. After 10 weeks, however, CLA had beneficial effects on glucose and insulin concentrations. At this time, CLA had no effect on the plasma TNFα concentration, but it markedly reduced the plasma adiponectin concentration. CLA and CLA enriched with either isomer raised the plasma triglyceride concentration during the first three weeks, but not subsequently. CLA enriched with its trans-10, cis-12 isomer, but not with its cis-9, trans-11 isomer, stimulated PPARγ-mediated reporter gene activity; both isomers stimulated PPARα-mediated reporter gene activity.ConclusionsCLA initially decreased but subsequently increased insulin sensitivity in lepob/lepob mice. Activation of both PPARγ and PPARα may contribute to the improvement in insulin sensitivity. In the short term, however, another mechanism, activated primarily by trans-10, cis-12-CLA, which probably leads to reduced adipocyte number and consequently reduced plasma adiponectin concentration, may decrease insulin sensitivity.

Highlights

  • Studies in rodents and some studies in humans have shown that conjugated linoleic acid (CLA), especially its trans10, cis-12 isomer, reduces body fat content

  • We describe activation of peroxisomal proliferator-activated receptor-γ (PPARγ) by t10, c12 but not by c9, t11-CLA, whereas PPARα was activated by both isomers

  • Weight gain Inclusion of CLA in the diet of genetically obese mice reduced their body weight, or weight gain compared to mice fed on a diet containing a similar amount of sunflower oil (Figure 1)

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Summary

Introduction

Studies in rodents and some studies in humans have shown that conjugated linoleic acid (CLA), especially its trans, cis-12 isomer, reduces body fat content. Some but not all studies in mice and humans (though none in rats) have found that CLA promotes insulin resistance. CLA may be of benefit in cancer, atherosclerosis and possibly some disorders of the immune system. It reduces weight gain and fat accretion in rats and mice. More marked effects of CLA on body weight and body composition have been obtained in rats and especially mice, possibly because the rate of energy expenditure relative to energy stores is much higher in rodents than in humans

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