scholarly journals Resistance to hepatic action of vasopressin in genetically obese (ob/ob) mice

1976 ◽  
Vol 160 (1) ◽  
pp. 23-28 ◽  
Author(s):  
D A Hems ◽  
G Y Ma
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Inborn Error ◽  
Cholesterol Synthesis ◽  
Acid Synthesis ◽  
Hepatic Glycogen ◽  
Perfused Liver ◽  
Obese Mice ◽  
Hepatic Action ◽  
Glycogen Breakdown

1. Fatty acid synthesis, measured in the perfused liver of genetically obese (ob/ob) mice with 3H2O or [14C]actate, did not show the inhibition by [8-arginine]vasopressin (antidiuretic hormone) that is observed in livers from normal mice. 2. Hepatic glycogen breakdown in obese mice was stimuulated by vasopressin, but not as extensively as in lean mice. 3. If obese mice received a restricted amount of food, then fatty acid synthesis still did not respond to vasopressin, but glycogen breakdown was fully stimulated. 4. Cholesterol synthesis was not inhibited by vasopressin in livers from obese mice. 5. Vasopressin inhibited fatty acid synthesis in intact lean mice, but not in obese animals. 6. These results suggest that genetic obesity could be due to an inborn error within the mechanisms (other than adenylate cyclase) which mediate responses to extracellular effectors.

scholarly journals Effects of glucagon and insulin on fatty acid synthesis and glycogen degradation in the perfused liver of normal and genetically obese (ob/ob) mice

1978 ◽  
Vol 174 (3) ◽  
pp. 761-768 ◽  
Author(s):  
G Y Ma ◽  
C D Gove ◽  
D A Hems
Keyword(s):  
Fatty Acid ◽  
Food Deprivation ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Biosynthesis ◽  
Glycogen Metabolism ◽  
Acid Synthesis ◽  
Significant Inhibition ◽  
Perfused Liver ◽  
Glucagon And Insulin ◽  
Glycogen Breakdown

1. Rapid effects of hormones on glycogen metabolism and fatty acid synthesis in the perfused liver of the mouse were studied. 2. In perfusions lasting 2h, of livers from normal mice, glucagon in successive doses, each producing concentrations of 10(-10) or 10(-9)M, inhibited fatty acid and cholesterol synthesis. In perfusions lasting 40–50 min, in which medium was not recycled, inhibition of fatty acid synthesis was only observed with glucagon at concentrations greater than 10(-9)M. This concentration was about two orders of magnitude higher than that required for the stimulation of glycogen breakdown. Glucagon did not inhibit the activity of acetyl-CoA carboxylase, assayed 10 or 20 min after addition of glucagon (10(-9) or 10(-10)M). It is proposed that the action of glucagon on hepatic fatty acid biosynthesis could be secondary in time to depletion of glycogen. Insulin prevented the effect of glucagon (10(-10)M) on glycogenolysis, but not that of vasopressin. 3. Livers of genetically obese (ob/ob) mice did not show significant inhibition of lipid biosynthesis in response to glucagon, although there was normal acceleration of glycogen breakdown. This resistance to glucagon action was not reversed by food deprivation. Livers of obese mice exhibited resistance to the counteraction by insulin of glucagon-stimulated glycogenolysis, which was reversible by partial food deprivation.

scholarly journals Synthesis of fatty acids in the perfused mouse liver

1974 ◽  
Vol 142 (3) ◽  
pp. 611-618 ◽  
Author(s):  
D. Michael W. Salmon ◽  
Neil L. Bowen ◽  
Douglas A. Hems
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Saturated Fatty Acids ◽  
Carbon Sources ◽  
Acid Synthesis ◽  
Hepatic Glycogen ◽  
Total Rate ◽  
Glucose Carbon

1. Fatty acid synthesis de novo was measured in the perfused liver of fed mice. 2. The total rate, measured by the incorporation into fatty acid of3H from3H2O (1–7μmol of fatty acid/h per g of fresh liver), resembled the rate found in the liver of intact mice. 3. Perfusions with l-[U-14C]lactic acid and [U-14C]glucose showed that circulating glucose at concentrations less than about 17mm was not a major carbon source for newly synthesized fatty acid, whereas lactate (10mm) markedly stimulated fatty acid synthesis, and contributed extensive carbon to lipogenesis. 4. The identification of 50% of the carbon converted into newly synthesized fatty acid lends further credibility to the use of3H2O to measure hepatic fatty acid synthesis. 5. The total rate of fatty acid synthesis, and the contribution of glucose carbon to lipogenesis, were directly proportional to the initial hepatic glycogen concentration. 6. The proportion of total newly synthesized lipid that was released into the perfusion medium was 12–16%. 7. The major products of lipogenesis were saturated fatty acids in triglyceride and phospholipid. 8. The rate of cholesterol synthesis, also measured with3H2O, expressed as acetyl residues consumed, was about one-fourth of the basal rate of fatty acid synthesis. 9. These results are discussed in terms of the carbon sources of hepatic newly synthesized fatty acids, and the effect of glucose, glycogen and lactate in stimulating lipogenesis, independently of their role as precursors.

EFFECT OF ALLOXAN, INSULIN, AND THYROXINE ON CHOLESTEROL AND FATTY ACID SYNTHESIS BY RAT LIVER HOMOGENATES

1957 ◽  
Vol 35 (1) ◽  
pp. 15-23 ◽  
Author(s):  
J. F. Scaife ◽  
B. B. Migicovsky
Keyword(s):  
Carbon Dioxide ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Rat Liver ◽  
Fatty Acid Synthesis ◽  
Sodium Acetate ◽  
Cholesterol Synthesis ◽  
Acid Synthesis ◽  
Liver Homogenates ◽  
Vitro Effect

The in vitro effect of alloxan and insulin on the synthesis of cholesterol and fatty acids from 1-C14-sodium acetate by rat liver homogenates has been examined. Alloxan caused a reduction in the incorporation of acetate into cholesterol, fatty acids, and C14O2, but an increase in the oxygen consumption and carbon dioxide production. The addition of insulin to homogenates caused a reduction in cholesterol synthesis but an increase in fatty acid synthesis both for normal and diabetic animals. Homogenates from thyrotoxic rats exhibited a marked reduction in cholesterol synthesis when compared with normal animals. C14O2 production by homogenates from starved rats was appreciably lower than for those from normal animals. With this exception no appreciable difference was found in the oxygen uptake, carbon dioxide, or C14O2 production in homogenates from normal, starved, thyroxine-treated, or diabetic animals. Synthesized cholesterol was found to be located principally in the particulate matter of the homogenates after they had been incubated with 1-C14-sodium acetate. Homogenates from starved rats showed no greater tendency to degrade preformed cholesterol during incubation than did those from normal rats.

EFFECT OF ALLOXAN, INSULIN, AND THYROXINE ON CHOLESTEROL AND FATTY ACID SYNTHESIS BY RAT LIVER HOMOGENATES

1957 ◽  
Vol 35 (1) ◽  
pp. 15-23 ◽  
Author(s):  
J. F. Scaife ◽  
B. B. Migicovsky
Keyword(s):  
Carbon Dioxide ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Rat Liver ◽  
Fatty Acid Synthesis ◽  
Sodium Acetate ◽  
Cholesterol Synthesis ◽  
Acid Synthesis ◽  
Liver Homogenates ◽  
Vitro Effect

The in vitro effect of alloxan and insulin on the synthesis of cholesterol and fatty acids from 1-C14-sodium acetate by rat liver homogenates has been examined. Alloxan caused a reduction in the incorporation of acetate into cholesterol, fatty acids, and C14O2, but an increase in the oxygen consumption and carbon dioxide production. The addition of insulin to homogenates caused a reduction in cholesterol synthesis but an increase in fatty acid synthesis both for normal and diabetic animals. Homogenates from thyrotoxic rats exhibited a marked reduction in cholesterol synthesis when compared with normal animals. C14O2 production by homogenates from starved rats was appreciably lower than for those from normal animals. With this exception no appreciable difference was found in the oxygen uptake, carbon dioxide, or C14O2 production in homogenates from normal, starved, thyroxine-treated, or diabetic animals. Synthesized cholesterol was found to be located principally in the particulate matter of the homogenates after they had been incubated with 1-C14-sodium acetate. Homogenates from starved rats showed no greater tendency to degrade preformed cholesterol during incubation than did those from normal rats.

Effect of diabetes on cholesterol and fatty acid synthesis in the rat aorta

1960 ◽  
Vol 198 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Daniel W. Foster ◽  
Marvin D. Siperstein
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Cholesterol Synthesis ◽  
Acid Synthesis ◽  
Rat Aorta ◽  
Diabetic Rats ◽  
Liver Cholesterol ◽  
Hepatic Cholesterol ◽  
Hepatic Cholesterol Synthesis ◽  
Normal Controls

The synthesis of cholesterol and fatty acids from acetate-1-C14 was studied in the aortas and livers of 42 diabetic rats and their normal controls. Hepatic cholesterol synthesis was significantly increased in 13, decreased in 13, and unchanged in 16 of the 42 animals. Fatty acid synthesis was depressed in the liver in 39 of the 42 diabetic rats. Aortic cholesterogenesis was increased in only 2 of the 13 aortas from the same rats showing elevated hepatic cholesterol synthesis. Fatty acid synthesis was depressed in 21 of 42 aortas from the diabetic group. It is concluded, therefore, that the aorta is relatively resistant to stimulation of cholesterol synthesis by diabetes even when hepatic cholesterol synthesis in the same animal is elevated. Lipogenesis on the other hand is commonly depressed in the aorta as well as the liver. Cholesterol was purified through dibrominization and both normal and diabetic aortas were shown to be capable of carrying cholesterol synthesis to completion.

scholarly journals Studies in lipogenesis in vivo. Fatty acid and cholesterol synthesis during starvation and re-feeding

1966 ◽  
Vol 101 (3) ◽  
pp. 811-818 ◽  
Author(s):  
GR Jansen ◽  
ME Zanetti ◽  
CF Hutchison
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Intraperitoneal Injection ◽  
Cholesterol Synthesis ◽  
Liver Glycogen ◽  
Acid Synthesis ◽  
Tracer Dose ◽  
Intraperitoneal Dose

1. Lipogenesis in vivo has been studied in mice given a 250mg. meal of [U-(14)C]glucose (2.5muc) or given an intraperitoneal injection of 25mug. of [U-(14)C]glucose (2.0muc). 2. The ability to convert a [U-(14)C]glucose meal into fatty acid was not significantly depressed by 6-7hr. of starvation. In contrast, incorporation of (14)C into fatty acid in the liver after the intraperitoneal dose of [(14)C]glucose was depressed by 80% and by more than 90% by 1 and 2hr. of starvation respectively. Carcass fatty acid synthesis from the [U-(14)C]glucose meal was not depressed by 12hr. of starvation, whereas from the tracer dose of [U-(14)C]glucose the depression in incorporation was 80% after 6hr. of starvation. 3. Re-feeding for 3 days, after 3 days' starvation, raised fatty acid synthesis and cholesterol synthesis in the liver fivefold and tenfold respectively above the levels in non-starved control mice. These increases were associated with an increased amount of both fatty acid and cholesterol in the liver. 4. After 18hr. of starvation incorporation of a [U-(14)C]glucose meal into carcass and liver glycogen were both increased threefold.

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