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Activation of leptin expression by an inhibitor of carnitine palmitoyltransferase-1

International Journal of Obesity volume 28, pages 649–651 (2004)Cite this article

Abstract

Leptin may regulate peripheral fatty acid oxidation and invoke a feedback mechanism that affects leptin expression in adipocytes. The objective of this study, therefore, was to determine whether inhibiting systemic fatty acid oxidation at the level of carnitine palmitoyltransferase-1 (CPT1) affects leptin expression. To accomplish this objective, fed or overnight fasted rats were treated with 2-tetradecylglycidic acid (TDGA), a specific, irreversible CPT1 inhibitor, and acute changes in rat epididymal leptin expression and serum leptin content were measured using Northern, RT–PCR, and radioimmunoassay analyses. Overnight fasting decreased both epididymal leptin mRNA content and serum leptin. Treating overnight fasted rats with TDGA increased both their epididymal leptin mRNA and their serum leptin significantly in a time- and concentration-dependent manner. TDGA affected neither epididymal leptin mRNA nor serum leptin in fed rats where systemic fatty acid oxidation is low. These results support the conclusion that CPT1-linked fatty acid oxidation is a key modulator of leptin expression in fasting rats.

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References

  1. Ahima RS, Flier JS . Leptin. Ann Rev Physiol 2000; 62: 413–437.

    Article  CAS  Google Scholar 

  2. Vernon Rayner D, Trayhurn P . Regulation of leptin production: sympathetic nervous system interactions. J Mol Med 2001; 79: 8–20.

    Article  Google Scholar 

  3. Levine AS, Billington CJ . Do circulating leptin concentrations reflect body adiposity of energy flux? Am J Clin Nutr 1998; 68: 761–762.

    Article  CAS  Google Scholar 

  4. Minokoshi Y, Kim Y-B, Peroni OD, Fryer LGD, Muller C, Carling D, Kahn BB . Leptin stimulates fatty acid oxidation by activating AMP-activated protein kinase. Nature 2002; 415: 339–343.

    Article  CAS  Google Scholar 

  5. Muoio DM, Dohm GL, Fiedorek FT, Tapscott EB, Coleman RA . Leptin directly alters lipid partitioning in skeletal muscle. Diabetes 1997; 46: 1360–1363.

    Article  CAS  Google Scholar 

  6. Shimabukuro M, Koyama K, Chen G, Wand M-Y, Trieu F, Lee Y, Newgard CB, Unger RH . Direct antidiabetic effect of leptin through triglyceride depletion of tissues. Proc Natl Acad Sci USA 1997; 94: 4637–4641.

    Article  CAS  Google Scholar 

  7. Atkinson LL, Fischer MA, Lopaschuk GD . Leptin activates cardiac fatty acid oxidation independent of changes in the AMP-activated protein kinase-acetyl-CoA carboxylase-malonyl-CoA axis. J Biol Chem 2002; 277: 29424–29430.

    Article  CAS  Google Scholar 

  8. Worm D, Vinten J, Vaag A, Henriksen JE, Beck-Nielsen H . The nicotinic acid analogue acipomox increases plasma leptin and decreases fatty acid in type 2 diabetes patients. Eur J Endocrinol 2000; 143: 389–395.

    Article  CAS  Google Scholar 

  9. Wang-Fisher Y-L, Han J, Guo W . Acipomox stimulates leptin production from isolated rat adipocytes. J Endocrinol 2002; 174: 267–272.

    Article  CAS  Google Scholar 

  10. Kiorpes TC, Hoerr D, Ho W, Weaner LE, Inman MG, Tutwiler GF . Identification of 2-tetradecylglycidyl coenzyme A as the active form of methyl 2-tetradecylglycidate (methyl palmoxirate) and its characterization as an irreversible, active site-directed inhibitor of carnitine palmitoyltransferase A in isolated rat liver mitochondria. J Biol Chem 1984; 259: 9750–9755.

    CAS  PubMed  Google Scholar 

  11. Wolkowicz P, Urthaler F, Forrest C, Shen H, Durand J, Wei C-C, Oparil S, Dell'Italia LJ . 2-Tetradecylglycidic acid, an inhibitor of carnitine palmitoyltransferase-1, induces myocardial hypertrophy via the AT1 receptor. J Mol Cell Cardiol 1999; 31: 1405–1412.

    Article  CAS  Google Scholar 

  12. Grenett HE, Bounelis P, Fuller GM . Identification of a human cDNA with high homology to yeast omnipotent suppressor 45. Gene 1992; 110: 239–243.

    Article  CAS  Google Scholar 

  13. Grenett HE, Wolkowicz PE, Benza RL, Tresnak JK, Wheeler CG, Booyse FM . Identification of a 251-bp fragment of the PAI-1 gene promoter that mediates the ethanol-induced suppression of PAI-1 expression. Alcohol: Clin Exp Res 2001; 25: 629–636.

    Article  CAS  Google Scholar 

  14. Margetic S, Gazzola C, Pegg GG, Hill RA . Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 2002; 26: 1407–1433.

    Article  CAS  Google Scholar 

  15. Shimokawa T, Kumar MV, Lane MD . Effect of fatty acid synthase inhibitor on food intake and expression of hypothalamic neuropeptides. Proc Natl Acad Sci USA 2002; 99: 66–71.

    Article  CAS  Google Scholar 

  16. Loftus TM, Jaworsky DE, Frehywot GL, Townsend CA, Ronnett GV, Lane MD, Kuhajda FP . Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 2000; 288: 2379–2781.

    Article  CAS  Google Scholar 

  17. Martin RJ, Bird MI, Saggerson ED, Munday LA, Clark JB . Enzyme activities in regions of the hypothalamus. J Neurochem 1987; 48: 738–740.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants from the American Diabetes Association, NIH (HL-57965) and the UAB Clinical Nutrition Research Center to PEW.

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Authors and Affiliations

  1. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    P Wolkowicz, H Grenett & F Urthaler

  2. Department of Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA

    M Belousova

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  1. P Wolkowicz
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  2. H Grenett
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  3. M Belousova
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  4. F Urthaler
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Correspondence to P Wolkowicz.

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Wolkowicz, P., Grenett, H., Belousova, M. et al. Activation of leptin expression by an inhibitor of carnitine palmitoyltransferase-1. Int J Obes 28, 649–651 (2004). https://doi.org/10.1038/sj.ijo.0802585

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  • DOI: https://doi.org/10.1038/sj.ijo.0802585

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