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J Biol Chem, Vol. 273, Issue 33, 20929-20934, August 14, 1998
From the Fatty acid cycling by chain shortening/elongation
in the peroxisomes is an important source of fatty acids for membrane
lipid synthesis. Its role in the homeostasis of nonessential fatty
acids is poorly understood. We report here a study on the cycling of saturated fatty acids and the effects of troglitazone in HepG2 cells in
culture using [U-13C]stearate or
[U-13C]oleate and mass isotopomer analysis. HepG2 cells
were grown in the presence of 0.7 mmol/liter
[U-13C]stearate or [U-13C]oleate, and in
the presence and absence of 50 µM troglitazone for
72 h. Fatty acids extracted from cell pellets after saponification were analyzed by gas chromatography/mass spectrometry. Peroxisomal
Fatty Acid Cycling in Human Hepatoma Cells and the Effects of
Troglitazone
,,,, and Harbor-UCLA Medical Center, Torrance,
California 90502 and ¶ UCLA School of Medicine,
Los Angeles, California 90024
-oxidation of uniformly 13C-labeled stearate (C18:0) and
oleate (C18:1) resulted in chain shortening and produced uniformly
labeled palmitate (C16:0) and palmitoleate (C16:1). In untreated cells,
16% of C16:0 was derived from C18:0 and 26% of C16:1 from C18:1 by
chain shortening. Such contributions were significantly increased by
troglitazone to 23.6 and 36.6%, respectively (p < 0.001). Desaturation of stearate contributed 67% of the oleate, while
reduction of oleate contributed little to stearate (2%). The
desaturation of C18:0 to C18:1 was not affected by troglitazone. Our
results demonstrated a high degree of recycling of C18:0 and C18:1 to
C16:0 and C16:1 through chain shortening and desaturation. Chain
shortening was accompanied by chain elongation in the synthesis of
other long chain fatty acids. Troglitazone specifically increased
recycling by peroxisomal -oxidation of C18 to C16 fatty acids, and
the interconversion of long chain fatty acids was associated with
reduced de novo lipogenesis.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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