E. J. Masoro

Effect of Adrenalectomy on Albumin-Palmitate-1-C14 Oxidation.∗

Summary Oxidation of albumin-palmitate-1-C14 (NEFA) to C14O2 was studied in shamoperated and adrenalectomized rats fasted for 12-18 hours. The C14O2 yield was approximately the same in both animal groups. The conclusion is drawn that ability of rat tissues to oxidize long-chain fatty acids is not affected by adrenalectomy. The C14O2 production from albumin-palmitate complex is not related either to size of animal or to endogenous metabolism, as shown by total CO2 production.

A study of the lipogenic inhibitory mechanisms induced by fasting

Abstract Cytoplasmic particles from livers of fasted rats inhibit fatty acid synthesis by the hepatic supernatant enzyme system. In contrast, the cytoplasmic particles from livers of fed rats stimulate lipogenesis by the supernatant system. The microsomes from livers of fasted rats have the most marked inhibitory activity, which is associated with a material that is protein in nature. The inhibition occurs at the acetyl carboxylase step. Restriction of the amount of ATP available for this reaction by means of an increased microsomal ATPase is probably an important part of the inhibitory action. A microsomal interaction with the particle-free supernatant is also involved in the inhibitory action. The possible physiological significance of lipogenic inhibitors is discussed.

A COMPARISON OF FATTY ACID SYNTHESIS BY LIVER AND KIDNEY.

Summary The lipogenic activity of liver and kidney was compared. Kidney slices synthesize fatty acids at a considerably slower rate than do liver slices; an approximate estimate would place the rate of kidney slice lipogenesis at about 10-20% that of the liver slice. Kidney tissue appears to have a lower level of fatty acid synthesizing enzymes than liver but the difference in lipogenic rate of the intact cell is probably related to other factors as well. Kidney cytoplasmic particles suppress lipogenesis in kidney particle-free supernatant while liver cytoplasmic particles stimulate kidney particle-free supernatant lipogenesis, Thus, the presence of cytoplasmic particles in the kidney that inhibit rather than stimulate fatty acid synthesis probably is also related to difference in lipogenic activity between liver and kidney slices.

The regulation of hepatic acetate-1-C14 metabolism by short-chain fatty acids.

Abstract Propionate, isobutyrate, and caproate inhibited all phases of acetate-1-C 14 metabolism studied. Butyrate suppressed acetate utilization and oxidation without affecting the incorporation of acetate-1-C 14 into fatty acids. This evidence suggests that butyrate increases lipogenesis from acetyl groups. It is proposed that fatty acids exert a regulatory action on acetyl metabolism.

Inhibitory mechanisms in the control of lipogenesis

Synthesis of fatty acids by supernatant prepared from livers of fed rats was measured when various cytoplasmic particles of livers from fed or fasted rats were present. Microsomal inhibition of lipogenesis occurs at the acetyl-CoA carboxylase (acetyl-CoA:CO2 ligase (ADP), EC 6.4.1.2) step and involves at least two mechanisms: The action of a microsomal ATPase (ATP phosphohydrolase) which is elevated in fasting and an unidentified action upon the enzyme acetyl-CoA carboxylase. Inhibition by “light-” and by “intermediate” microsome fractions were tested separately. The inhibition due to the “light” microsomes was completely abolished by an ATP-generating system, indicating that the inhibitory mechanism here is ATP removal. Inhibition by intermediate fraction was only partially abolished by an ATP-generating system, indicating that both ATPase activity and interaction with the enzymes in the supernatant had occurred. Both microsomal fractions were more inhibitory when obtained from fasted rats than those from fed rats. The mitochondrial inhibition did not affect the reaction of the fatty acid synthetase system and probably acts directly on the enzyme acetyl-CoA carboxylase. Mitochondria from fasted rats were more inhibitory than those from fed rats.

Alteration of the pattern of hepatic carbohydrate metabolism by propionate and butyrate

Abstract Butyrate and propionate caused a reduction in C 14 O 2 and lipide-C 14 production from evenly labeled glucose, glucose-1-C 14 , glucose-6-C 14 , and lactate-2-C 14 . Unlike the action of these acids on acetate metabolism, the inhibition of lipogenesis from glucose and lactate was more severe than the reduction in oxidation of these compounds. These striking differences between the inhibitory actions of butyrate and propionate on hepatic acetate metabolism on the one hand and hepatic carbohydrate metabolism on the other seem to suggest that the metabolic path of the C-2 fragment derived from these two sources must differ.

Effect of cold acclimation on vitamin A metabolism.

Summary Hepatic vit. A levels are much higher in cold-acclimated rats than in rats maintained at 25°C. This increase in hepatic vit. A content does not stem from a sparing action induced by cold acclimation but is rather a simple corollary of increased food consumption that accompanies cold-exposure. Moreover, evidence is presented which suggests that the amount of vit. A needed for rats to live at 0-2 °C is not markedly greater than the amount needed to live at 25 °C.

Effects of Short Chain Fatty Acids on Hepatic Acetate Metabolism in Cold Exposure and Fasting.

Summary and conclusions Butyrate, isobutyrate, propionate, caproate, and acetoacetate failed to reverse the block in acetate-1-C14 oxidation found in liver slices from rats fasted at 0-2°C for 24 hours. It appears that the ability of glucose and pyruvate to increase the acetate oxidation activity of these liver slices is related to a specific step in carbohydrate metabolism rather than solely to the fact that carbohydrates are excellent sources of energy.

Effect of Cold-Exposure and Fasting on Pathways of Hepatic Glucose Oxidation.∗

Summary Metabolism of glucose-1-C14 and glucose-6-C14 was studied in liver slices from control rats (fed at 25°C) and cold-fasted rats (fasted 24 hours at 0–2°C). Evidence is presented that suggests that carbohydrate metabolism is diverted towards the hexose monophosphate pathway in the liver of cold-fasted rats. The depressed hepatic fatty acid synthesis in the cold-fasted rat is discussed in the light of this new evidence on carbohydrate metabolism.