Nome Baker

Characteristics of the Cholesterol-Esterifying Activity in Normal and Atherosclerotic Rabbit Aortas

Esterification of cholesterol with [1-14C]palmityl-CoA by an atherosclerotic cell-free homogenate was approximately 16–50-fold greater than that by a normal cell-free homogenate for a given amount of protein in the homogenate. This difference was due to hyperactivity of the cholesterol-esterifying system in the atherosclerotic cell-free homogenate rather than to depletion of radioactive palmityl-CoA in the reaction mixture containing normal homogenate. Neither an activator of cholesterol esterification in the soluble fraction of the atherosclerotic aortic homogenate nor an inhibitor in the soluble fraction of the normal aortic homogenate could be demonstrated. The pH optimum within the pH range covered for esterification and the apparent Km values were approximately the same in normal and atherosclerotic microsomes, suggesting that the enzymes were probably the same. The results suggested a higher concentration or a higher activity of the enzyme in or on atherosclerotic microsomes. An alternative possibility is that high concentrations of free cholesterol in the atherosclerotic microsomes were responsible for the augmented cholesterol esterification. This possibility seems unlikely, because the observed 2.3-fold increase in the free cholesterol concentration should not produce a 25-fold increase in cholesterol esterification. The rate of cholesterol esterification by atherosclerotic microsomes varied with the substrate: oleyl-CoA > palmityl-CoA > linoleyl-CoA.

Turnover and fate of plasma free fatty acids in briefly-fasted lymphoma-bearing mice

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 breath14CO2 (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 breath14CO2 (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.

Comparison of Lipogenic Responses to Dietary Glucose in Selected Mouse Adipose Tissues

Rates of fatty acid synthesis from glucose-carbon (glucose-C) and all other 2-carbon (2-C) units were measured in three white adipose tissues sites of fasted and fed mice, which were given a test meal containing [U-14C]glucose. Total fatty acid synthesis was measured in all mice by intraperitoneal injection of 3H2O. In fasted-refed mice the rates of lipogenesis from glucose-C and all 2-C sources were much faster in popliteal than in epididymal fat. Most of the newly synthesized fatty acids were derived from glucose-C. However, in fed-refed mice these differences between the sites were minimal, and all the absolute rates were much higher than those found in fasted-refed mice. This suggested that the adipose tissue in the three sites did not have different physiological roles. Variability in the actual rates of lipogenesis, from one experiment to another, in fasted-refed mice could be attributed to small differences in the periods of fasting, before the mice were given the test meal.