The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue. Effects of altered dietary and hormonal conditions

Abstract

1. Epididymal adipose tissues obtained from rats that had been previously starved, starved and refed a high fat diet for 72h, starved and refed bread for 144h or fed a normal diet were incubated in the presence of insulin+glucose or insulin+glucose+acetate. 2. Measurements were made of the whole-tissue concentrations of hexose phosphates, triose phosphates, glycerol 1-phosphate, 3-phosphoglycerate, 6-phosphogluconate, adenine nucleotides, acid-soluble CoA, long-chain fatty acyl-CoA, malate and citrate after 1h of incubation. The release of lactate, pyruvate and glycerol into the incubation medium during this period was also determined. 3. The rates of metabolism of glucose in the hexose monophosphate pathway, the glycolytic pathway, the citric acid cycle and into glyceride glycerol, fatty acids and lactate+pyruvate were also determined over a 2h period in similarly treated tissues. The metabolism of acetate to CO(2) and fatty acids in the presence of glucose was also measured. 4. The activities of acetyl-CoA carboxylase, fatty acid synthetase and isocitrate dehydrogenase were determined in adipose tissues from starved, starved and fat-refed, and alloxan-diabetic animals and also in tissues from animals that had been starved and refed bread for up to 96h. Changes in these activities were compared with the ability of similar tissues to incorporate [(14)C]glucose into fatty acids in vitro. 5. The activities of acetyl-CoA carboxylase and fatty acid synthetase roughly paralleled the ability of tissues to incorporate glucose into fatty acids. 6. Rates of triglyceride synthesis and fatty acid synthesis could not be correlated with tissue concentrations of long-chain fatty acyl-CoA, citrate or glycerol 1-phosphate. In some cases changes in phosphofructokinase flux rates could be correlated with changes in citrate concentration. 7. The main lesion in fatty acid synthesis in tissues from starved, starved and fat-refed, and alloxan-diabetic rats appeared to reside at the level of pyruvate utilization and to be related to the rate of endogenous lipolysis. 8. It is suggested that pyruvate utilization by the tissue may be regulated by the metabolism of fatty acids within the tissue. The significance of this in directing glucose utilization away from fatty acid synthesis and into glyceride-glycerol synthesis is discussed.

Regulation of Mammalian Fatty-Acid Synthetase. The Roles of Carbohydrate and Insulin

“…Although diabetic rats feeding freely con- Tables 1 and 2), confirming previous reports (2,3,18). To avoid the problems of unequal food consumption in the experiments summarized in Tables 1 and 2, all animals were fed by gastric intubation.…”

Acetoacetyl‐CoA synthetase; a lipogenic enzyme in rat tissues

“…In addition, thiolase in liver cytosol does not change in activity with starvation [21]. The low activity of acetoacetyl-CoA synthetase in mammary gland and adipose tissue cytosolic fractions compared with the rates of fatty acid synthesis observed in these tissues [22,23] would also seem to preclude a major role of acetoacetyl-CoA synthetase in providing C2-units for fatty acid synthesis in these tissues.…”

Insulin determines leptin responses during a glucose challenge in fed and fasted rats

“…12,24 It has been shown that leptin secretion is related to insulin-stimulated glucose uptake or metabolism in the adipocyte in vitro 11 and in vivo. 22,25 As fasting decreases the uptake and metabolism of glucose in adipose tissue, [26][27][28] this (in addition to the lower insulin responses) may be the mechanism for the lower leptin secretory response observed in the fasted rats. If leptin has a predominant role as a survival signal in response to starvation, 19 it may be important to maintain low serum leptin levels following fasting.…”