RESUMEN

To test for a regulatory defect in adipose triacylglycerol (essential) fatty acid mobilization in lymphoma-bearing mice, free [1-14C]linoleic acid/mouse serum albumin was injected iv into lymphoma-bearing and control mice, adapted to a reversed light cycle, and studied in three dietary states in the dark period. Mean daily food intake decreased in mice with small and large tumor burdens. Plasma free fatty acid (FFA) oxidation rates, which approximate FFA mobilization rates, were estimated by multicompartmental analysis (CONSAM). Oxidation of linoleate to CO2 was reduced significantly (85%) in ad libitum fed as compared to briefly fasted control mice but not in fed vs. fasted mice with large or small tumor burdens. However, plasma FFA oxidation rates to CO2 did not differ in briefly fasted tumor-bearing and pair-fed control mice. When re-fed a 250-mg test meal, briefly fasted mice with small tumors suppressed plasma free linoleic acid oxidation, as did controls. During simulated night, mildly anorexic, tumor-bearing mice with small tumor burdens mobilized essential fatty acids much faster than controls. This could explain body fat loss. The abnormally rapid rates of FFA (free linoleic acid) mobilization at night probably result from anorexia rather than from inability of food to suppress fat mobilization.

Asunto(s)

RESUMEN

Lymphoma-bearing mice have a circulating lipid-mobilizing factor, but increased plasma free fatty acid (FFA) turnover has not been demonstrable in earlier studies using postabsorptive tumor-bearing mice. We hypothesized that FFA mobilization in lymphoma-bearing mice is only elevated in fed mice and may best be observed at night (dark, reversed light cycle). AKR mice with early and advanced tumors (10(6) SL-3 lymphoma cells, i.p.) and controls were fed ad libitum (reversed light cycle, dark) or fasted 4 h (daylight, regular cycle), given injections of [14C]bicarbonate of [1-14C]palmitate-mouse serum albumin, i.v., and plasma [14C]FFA disappearance and/or breath 14CO2 were monitored. Plasma FFA mobilization, estimated by multicompartmental analysis (SAAM) of the oxidation rate was lower in fasted mice with advanced tumors [tumor, 9.5 +/- 6.0% (%SE); controls, 14 +/- 4.4% micrograms-atoms fatty acid-carbon/min/30 g body weight, n = 3 to 6 mice/time point/group]. Feeding reduced these rates 90% in control mice and 53% in mice with early tumors, but only 14% in mice with advanced tumors. Plasma FFA fractional catabolic rates were 2.5 times faster in fed mice with advanced tumors than in controls. Diminished suppression of fatty acid mobilization in fed tumor-bearing mice (at night) probably accounts partially for the body fat loss.

Asunto(s)

RESUMEN

Body fat loss during tumor growth may be due to increased mobilization of adipose triglycerides. Earlier work from this laboratory suggested that (i) lymphoma-bearing AKR mice have a circulating lipid mobilizing factor (LMF) which caused body fat loss during cancer growth; that (ii) fatty acids (FA) mobilized in these tumor-bearing (TB) mice were not oxidized to CO2 as in starved mice that lose their body fat; and that (iii) instead, the mobilized FA were sequestered by the lymphoma. We tested these hypotheses by injecting [1-14C]palmitate-albumin into lymphoma-bearing and control mice. We measured turnover of plasma FFA for 24 hr and predicted the cumulative conversion of tracer into breath 14CO2 (at 85 min) in the TB mice. Plasma FFA were mobilized more slowly in briefly fasted tumor-bearing mice than in controls with the same plasma FFA pool sizes. The fractional catabolic rate (FCR) (min-1) of plasma FFA turnover in both groups decreased during the night when the mice ate: postabsorptive controls, 1.07 (+/- 5.6%); fed controls, 0.25 (+/- 13%); postabsorptive TB, 0.53 (+/- 4.6%); fed TB, 0.29 (+/- 7.3%). Virtually all of the plasma FFA irreversible disposal in TB mice was accounted for as breath 14CO2 (30 to 40% I.D.), not as tumor lipids (1.1 +/- 0.22% I.D.). Thus, FFA oxidation to CO2 is the major fate of plasma FFA turnover in TB mice, and sequestration of FFA (palmitate) by tumor cells is a quantitatively minor process. The putative circulating LMF did not cause increased FFA mobilization in these lymphoma-bearing mice in the post-absorptive state.

Asunto(s)

RESUMEN

We have reexamined the concept of the irreversible disposal rate (IDR) or fractional catabolic rate (FCR) in relation to the oxidation of a major metabolic fuel, plasma free fatty acids (FFA), in mice. We measured the disappearance of intravenously injected [1-14C]palmitate complexed to mouse serum albumin from the circulation of normal mice fed ad libitum and fasted approximately 4 h before tracer injection. We also measured the appearance of expired 14CO2 in the breath. Using multicompartmental analyses (SAAM) we found that, in contrast to earlier studies in this and other mammals where the estimated IDR has always been two to three times greater than the oxidative rate, the IDR (FCR) corresponded closely to the fractional rate of plasma FFA oxidation to CO2. This rate could be estimated accurately in a study of 10- to 15-min duration. In an extended study (5-h duration) we obtained kinetic evidence of a major transport pathway that involves delayed recycling of FFA through at least several unidentified relatively slowly turning compartments.

Asunto(s)

RESUMEN

Concentrations of albumin in excess of 1% in the incubation mixture inhibited the elongation of added fatty acids and their incorporation into microsomal lipids whereas these reactions were not inhibited with endogenous microsomal membrane fatty acids. The results of these and other studies support the idea that such reactions of membrane lipid fatty acids with membrane-bound enzymes normally occur entirely within the membrane without release of free fatty acids to equilibrate with the fatty acid pool during the process.

Asunto(s)

RESUMEN

Using a technique in which substrate fatty acids are incorporated into microsomal membranes followed by comparison of their rates of desaturation with those of exogenous added fatty acids, it has been found that the desaturation rate may be greater for the membrane-bound substrate than for the added fatty acid. Moreover, the product of the membrane-bound substrate is incorporated into membrane phospholipid whereas the product of the exogenous substrate is found in di- and triacylglycerols and in free fatty acids, as well. These and other findings point to a normal sequence of reaction of membrane lipids with membrane-bounds substrates involving transfer of fatty acid from phospholipid to the coupled enzyme systems without facile equilibration with the free fatty acid pool.

Asunto(s)

Asunto(s)

Asunto(s)