Conjugated linoleic acid and hepatic lipogenesis in mouse: role of the mitochondrial citrate carrier

Alexandra W.C Einerhand,Sara Colombo,Vincenzo Zara,Laura Conte,Alessandra Ferramosca,Viviana Savy

doi:10.1194/jlr.m600138-jlr200

Alexandra W.C Einerhand, Sara Colombo + Show 4 more

Open Access

https://doi.org/10.1194/jlr.m600138-jlr200

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Abstract

Conjugated linoleic acid (CLA) is able to reduce adiposity by affecting lipid metabolism. In particular, CLA administration to mice reduces body fat mass with a concomitant lipid accumulation in the liver. We investigated the effects of CLA on the activity of the mitochondrial citrate carrier (CIC), which is implicated in hepatic lipogenesis. The transport activity of the CIC, measured both in intact mitochondria and in the proteoliposomes, progressively increased with the duration of CLA feeding. An increase in the CIC activity of approximately 1.7-fold was found in 16 week CLA-treated mice with respect to control animals. A kinetic analysis showed a 1.6-fold increase in the V(max) of citrate transport but no change in the K(m) value. Western blot experiments revealed an increase of approximately 1.7-fold in the expression of CIC after CLA treatment. A strict correlation between the increase in CIC activity and the stimulation of the cytosolic lipogenic enzymes was also found. These data indicate that the CIC may play a role in the onset of hepatic steatosis in CLA-fed mice by supplying the carbon source for de novo fatty acid synthesis.

Highlights

Conjugated linoleic acid (CLA) is able to reduce adiposity by affecting lipid metabolism
This study was designed to investigate a possible effect of CLA on the citrate carrier (CIC), which plays a key role in hepatic lipogenesis for several reasons: i) citrate is formed in the mitochondrial matrix mainly from dietary carbohydrates and is exported by the CIC to the cytosol, where citrate generates acetyl-CoA, the substrate for acetyl-coenzyme A carboxylase (ACC), the first enzymatic step of de novo fatty acid synthesis (Fig. 6); ii) citrate exported to the cytosol is the substrate for lipogenesis but is the positive allosteric modulator of ACC (Fig. 6); and iii) the activity of the CIC is modulated by dietary and hormonal factors
A progressive increase was found in the activities of the cytosolic lipogenic enzymes

Summary

Introduction

Conjugated linoleic acid (CLA) is able to reduce adiposity by affecting lipid metabolism. The transport activity of the CIC in mouse liver mitochondria and in the reconstituted system (proteoliposomes) was measured at the times indicated.

Results

Conclusion