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Journal of Lipid Research, Vol. 45, 1992-1999, November 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Demonstration of reverse fatty acid transport from rat cardiomyocytes

Byung-Hyun Park^*, Young Lee^*, Marlei Walton, Laurence Duplomb^* and Roger H. Unger^1,*,

^* Gifford Laboratories, Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390
The Mary Nell and Ralph B. Rogers Magnetic Resonance Center, Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390
VA North Texas Health Care System, 4500 South Lancaster Road, Dallas, TX 75216

¹ To whom correspondence should be addressed. e-mail: roger.unger{at}utsouthwestern.edu

Fatty acids flow from adipocytes to nonadipose tissues during fasting and exercise and normally are fully oxidized. To determine if nonadipose tissues can export unoxidized FA when FA influx exceeds oxidation, neonatal cardiomyocytes were cultured in 1 µCi ¹⁴C-palmitate in the presence of etomoxir to block oxidation. The cells took up and stored 25% of the radioactivity as ¹⁴C-triacylglycerol in 12 h, but 4.5% of the label was released in 3 h and comigrated with ¹⁴C-palmitate. Both uptake and release of radioactivity were increased by insulin and reduced by the nonspecific inhibitors of FA transporters phloretin and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Perfused hearts from etomoxir-treated lean rats released 221 ± 59 nmol/10 min of FA. Hearts from high-fat-fed lean rats released 366 ± 172 nmol/10 min (P < 0.05). Hearts from obese rats released 744 ± 260 and 1,578 ± 630 nmol/10 min at 8 and 12 weeks of age, respectively. Perfusion with insulin increased FA release by 32%.

In vitro and ex vivo findings suggest that nonadipose tissues such as myocardium can export FA when the unoxidized lipid content is excessive.

Abbreviations: FABP, fatty acid-binding protein; FAT/CD36, fatty acid transporter; ZDF, Zucker Diabetic Fatty [rat]

Supplementary key words free fatty acid • insulin • liporegulation • triacylglycerol

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