Abstract
Previous reports that rabbit adipose tissue does not synthesize fatty acids at significant rates led us to study in detail the pathways of lipogenesis and glyceroneogenesis in this tissue. We found that rabbit adipose tissue has a low capacity for denovo fatty acid synthesis from glucose but a high capacity for synthesis from pyruvate and acetate. The tissue can also convert pyruvate to glyceride-glycerol via the dicarboxylic acid shuttle and gluconeogenic pathways. Experiments with hydroxycitrate, a potent inhibitor of citrate cleavage enzyme, demonstrated that this is an obligatory enzyme in lipogenesis from pyruvate. The lipogenic system of rabbit adipose tissue resembles that of a ruminant in that it is adapted to utilize acetate rather than glucose. However, in contrast to ruminant tissues, the limited ability to convert glucose to fatty acid results not from a deficiency in the enzymes concerned with the transport of acetyl units out of the mitochondria but from a block prior to the level of pyruvate, most likely at the hexokinase and pyruvate kinase reactions.
Highlights
Previous reports that rabbit adipose tissue does not synthesize fatty acids at significant rates led us to study in detail the pathways of lipogenesis and glyceroneogenesis in this tissue
Preliminary experiments confirmed the observations of Di Girolamo and Rudman [1] that, in contrast to rat adipose tissue, rabbit adipose tissue was unresponsive to insulin and had a low capacity for converting glucose to fatty acid
It is believed that adipose tissue is an important site of lipogenesis in several species of mammals and that glucose is an important physiological precursor for de novo fatty acid synthesis [25]
Summary
Perirenal adipose tissue was removed as rapidly as possible, rinsed at 37°C [9] in Krebs-Henseleit bicarbonate buffer (lo), and gently blotted dry. T h e incubation media contained the various substrates in 2 ml of Krebs-Henseleit bicarbonate buffer, and the atmosphere consisted of 95% oxygen and 5% carbon dioxide. The hexane extract was washed twice with 10 ml of water and evaporated to dryness under N2. A portion of the extract was evaporated to dryness and radioactivity was determined by liquid scintillation spectrometry. The radioactivity in the aqueous phase was assumed to represent glyceride-glycerol, as water-soluble material present prior to saponification was removed by the procedure of Folch et al [12]. The protein content per wet weight of tissue was approximately the same in rat and rabbit, so expressing the results on a protein basis did not change the interpretation
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