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Inhibition of Fatty Acid Incorporation into Adipose Tissue Triglycerides in Ehrlich Ascites Tumor-bearing Mice¹

Research Service, Veterans Administration Medical Center, Los Angeles, California 90073, and Department of Medicine, UCLA School of Medicine, and Crump Institute for Medical Engineering, University of California at Los Angeles, Los Angeles, California 90024

Using a recently developed technique of direct tracer injection into selective adipose tissue sites (Baker et al., Mech. Ageing Dev., 27: 295–313, 1984), we have studied the esterification of free fatty acids (FFA) to triglyceride fatty acids in the epididymal fat pads of normal and Ehrlich ascites carcinoma-bearing mice. We have tested the hypothesis that, during Ehrlich ascites carcinoma growth, a defect develops, resulting in the inhibition of the esterification and incorporation of FFA into adipose tissue diglyceride and triglyceride fatty acids. Our technique allowed the measurement of the disappearance of [1-¹⁴C]palmitic acid as FFA and its incorporation into di- and triglyceride fatty acids over 1 h. Multicompartmental analysis was used to compute the fractional rates of esterification and turnover. Using measured FFA pool sizes and assuming near-steady-state conditions, we estimated the transport rates (mass/time) of fatty acid esterification and turnover.

Our results indicate that, compared to controls (normal mice), the epididymal fat pads of mice bearing early (5-day) and advanced (9-day) Ehrlich ascites carcinoma, respectively, show: 65% and near complete (99%) decreases in the fractional rates of FFA esterification; about 2- and 24-fold increases in the FFA pool sizes; and 40% and 70% decreases in the transport rates of esterification.

¹ This work was supported by NIH USPHS Grant CA 15813 and Veterans Administration research.

Intramural computing support was obtained from the School of Medicine, UCLA. The modeling work was conducted using the SAAM program on the IBM 3033 computer at the UCLA Office of Academic Computing.

² To whom requests for reprints should be addressed, at Liver Research Laboratory, VA Wadsworth Medical Center, Bldg. 115, Rm. 316, Los Angeles, CA 90073.

³ Present address: Department of Medicine, UCSD Medical Center (H 811C), 225 Dickinson St., San Diego, CA 92103.

Received 4/29/85. Revised 8/26/85. Accepted 10/ 2/85.