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Changes in FAT/CD36, UCP2, UCP3 and GLUT4 gene expression during lipid infusion in rat skeletal and heart muscle

International Journal of Obesity volume 26, pages 838–847 (2002)Cite this article

Abstract

Objective: It has been reported that an increased availability of free fatty acids (NEFA) not only interferes with glucose utilization in insulin-dependent tissues, but may also result in an uncoupling effect of heart metabolism. We aimed therefore to investigate the effect of an increased availability of NEFA on gene expression of proteins involved in transmembrane fatty acid (FAT/CD36) and glucose (GLUT4) transport and of the uncoupling proteins UCP2 and 3 at the heart and skeletal muscle level.

Study Design: Euglycemic hyperinsulinemic clamp was performed after 24 h Intralipid® plus heparin or saline infusion in lean Zucker rats. Skeletal and heart muscle glucose utilization was calculated by 2-deoxy-[1-3H]-D-glucose technique. Quantification of FAT/CD36, GLUT4, UCP2 and UCP3 mRNAs was obtained by Northern blot analysis or RT-PCR.

Results: In Intralipid® plus heparin infused animals a significant decrease in insulin-mediated glucose uptake was observed both in the heart (22.62±2.04 vs 10.37±2.33 ng/mg/min; P<0.01) and in soleus muscle (13.46±1.53 vs 6.84±2.58 ng/mg/min; P<0.05). FAT/CD36 mRNA was significantly increased in skeletal muscle tissue (+117.4±16.3%, P<0.05), while no differences were found at the heart level in respect to saline infused rats. A clear decrease of GLUT4 mRNA was observed in both tissues. The 24 h infusion of fat emulsion resulted in a clear enhancement of UCP2 and UCP3 mRNA levels in the heart (99.5±15.3 and 80±4%) and in the skeletal muscle (291.5±24.7 and 146.9±12.7%).

Conclusions: As a result of the increased availability of NEFA, FAT/CD36 gene expression increases in skeletal muscle, but not at the heart level. The augmented lipid fuel supply is responsible for the depression of insulin-mediated glucose transport and for the increase of UCP2 and 3 gene expression in both skeletal and heart muscle.

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Acknowledgements

This work was supported by a grant of ‘Ricerca Finalizzata della Regione Veneto’ and by MURST (Ministero della Ricerca Scientifica e Tecnologica) grant no. 9806241798006 to GF and grant no. 980624179800 to MOC. We thank Mrs Marilena Tormene and Mrs Sonia Leandri for the expert technical assistance.

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Authors and Affiliations

  1. Department of Medical and Surgical Sciences, Internal Medicine, University of Padova, Padova, Italy

    R Vettor, R Fabris, R Serra, AM Lombardi, M Granzotto, MO Marzolo, G Federspil & E Nisoli

  2. Department of Preclinical Sciences, Center for Study and Research on Obesity, LITA Vialba, L. Sacco Hospital, University of Milano, Milano, Italy

    C Tonello & MO Carruba

  3. CNRS/CEREMOD, UPR 9078, Meudon, France

    D Ricquier

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  1. R Vettor
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Vettor, R., Fabris, R., Serra, R. et al. Changes in FAT/CD36, UCP2, UCP3 and GLUT4 gene expression during lipid infusion in rat skeletal and heart muscle. Int J Obes 26, 838–847 (2002). https://doi.org/10.1038/sj.ijo.0802005

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