Effect of Hyperthyroidism on Hepatic Lipogenesis in Rats: Studies in Vivo and in Vitro

1984 ◽  
Vol 67 (4) ◽  
pp. 457-460
Author(s):  
Amal S. Al-Saadi ◽  
J. Stewart Orr ◽  
Anthony W. Goode ◽  
Mary C. Sugden
Keyword(s):  
Carbon Flux ◽  
Hepatic Lipogenesis ◽  
Glycogen Depletion ◽  
Extrahepatic Tissues ◽  
Lactate And Pyruvate ◽  
Per Se

1. Lipogenic rates (measured with 3H2O) in hepatocytes from fed or starved euthyroid rats were similar in magnitude to those measured in livers in vivo. Hepatic lipogenesis in vivo in fed triiodothyronine (T3)-treated rats was greater than in fed control rats, but rates in vitro were only 16% of those of control rats. It is concluded that hepatic lipogenesis in vivo in T3-treated rats utilizes precursors from extrahepatic tissues. 2. Glycogen depletion of hepatocytes from fed control rats decreased lipogenesis, and rates were then similar to those in hepatocytes from fed T3-treated rats. Addition of lactate (2 mmol/l) and pyruvate (0.2 mmol/l) had little stimulatory effect on lipogenesis in hepatocytes from fed control rats, but increased lipogenesis in glycogen-depleted hepatocytes (by 86%), hepatocytes from starved rats (by 25%) and hepatocytes from T3-treated rats (by 60%). 3. In the presence of lactate and pyruvate, 3-mercaptopicolinate (3-MPA) (an inhibitor of gluconeogenesis) did not affect lipogenesis in hepatocytes from fed control rats but substantially increased lipogenesis in hepatocytes from starved euthyroid rats or fed hyperthyroid rats. Thus, in hepatocytes from starved euthyroid rats or fed hyperthyroid rats gluconeogenesis competes with lipogenesis for available precursors (lactate and pyruvate). In contrast, in fed rats carbon flux is predominantly towards lipogenesis. 4. Effects of 3-MPA in the presence of lactate and pyruvate were much less in glycogen-depleted cells from fed rats than in hepatocytes from starved or T3-treated rats. Thus glycogen depletion per se does not cause a redirection of carbon flux.

scholarly journals Considerations when investigating lncRNA function in vivo

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Andrew R Bassett ◽  
Asifa Akhtar ◽  
Denise P Barlow ◽  
Adrian P Bird ◽  
Neil Brockdorff ◽  
...  
Keyword(s):  
Normal Cell ◽  
Regulatory Elements ◽  
Genomic Locus ◽  
Cellular Processes ◽  
Cell Processes ◽  
Non Coding Rnas ◽  
Per Se ◽  
Dna Regulatory Elements

Although a small number of the vast array of animal long non-coding RNAs (lncRNAs) have known effects on cellular processes examined in vitro, the extent of their contributions to normal cell processes throughout development, differentiation and disease for the most part remains less clear. Phenotypes arising from deletion of an entire genomic locus cannot be unequivocally attributed either to the loss of the lncRNA per se or to the associated loss of other overlapping DNA regulatory elements. The distinction between cis- or trans-effects is also often problematic. We discuss the advantages and challenges associated with the current techniques for studying the in vivo function of lncRNAs in the light of different models of lncRNA molecular mechanism, and reflect on the design of experiments to mutate lncRNA loci. These considerations should assist in the further investigation of these transcriptional products of the genome.

Glucagon increases urinary oxalate excretion in the guinea pig

1995 ◽  
Vol 269 (3) ◽  
pp. E568-E574 ◽  
Author(s):  
R. P. Holmes ◽  
C. H. Hurst ◽  
D. G. Assimos ◽  
H. O. Goodman
Keyword(s):  
Hepatic Metabolism ◽  
Enzymatic Conversion ◽  
Urinary Oxalate ◽  
Oxalate Excretion ◽  
Lactate And Pyruvate ◽  
Urinary Oxalate Excretion ◽  
Glyoxylate Aminotransferase ◽  
Oxalate Synthesis

Factors that influence hepatic oxalate synthesis are poorly defined. Hormones are important regulators of hepatic metabolism and could potentially be involved. The effects of hyperglucagonemia were examined in guinea pigs injected with either saline or pharmacological doses of glucagon for 4 days. Glucagon treatment increased mean urinary oxalate excretion by 77% in male and 34% in female animals. The levels of hepatic peroxisomal enzymes involved in oxalate synthesis declined with glucagon treatment, but experiments with isolated peroxisomes indicated that oxalate synthesis in vitro was unaffected. Glucagon decreased hepatic alanine levels by 66%, lactate by 69%, and pyruvate by 73%, but glycolate and glyoxylate levels were unaffected. This decrease in alanine would substantially lower the activity of alanine-to-glyoxylate aminotransferase activity in vivo and make more glyoxylate available for oxalate synthesis. The decrease in lactate and pyruvate concentrations would stimulate the enzymatic conversion of glyoxylate to oxalate and may account for the increase in oxalate synthesis without an increase in glyoxylate concentration. These results demonstrate that hepatic oxalate synthesis is influenced by metabolic changes and that alterations in hepatic alanine, lactate, and pyruvate concentrations may be important elements.

Effect of CO2/pH on the aldosterone response to hypoxia in bovine adrenal cells in vitro

1993 ◽  
Vol 265 (4) ◽  
pp. R820-R825
Author(s):  
H. Raff ◽  
B. Jankowski
Keyword(s):  
Respiratory Acidosis ◽  
Inhibitory Effect ◽  
Zona Glomerulosa ◽  
Ang Ii ◽  
Adrenal Cells ◽  
Aldosterone Production ◽  
Per Se ◽  
Air Control

Acidosis increases and hypoxia decreases aldosterone production from the adrenal zona glomulerosa in vivo, in situ, and in vitro. These effects appear to be located at different steps in the steroidogenic process. Because respiratory acidosis and hypoxemia are common sequelae of chronic lung disease, the present experiments evaluated the interaction of hypoxia and CO2 (with uncompensated or compensated extracellular pH) on aldosteronogenesis in vitro. Bovine adrenal zona glomerulosa cells were stimulated with angiotensin II (ANG II) or adenosine 3',5'-cyclic monophosphate under room air control (21% O2-0% CO2), CO2 per se (21% O2-10% CO2), hypoxia per se (10% O2-0% CO2), and the combination of CO2 and hypoxia (10% O2-10% CO2). Furthermore, under CO2, pH was either allowed to decrease from 7.2 to 6.8 (uncompensated) or its decrease was minimized (> 7.05) with NaOH (compensated). CO2 without pH compensation led to a significant increase in ANG II-stimulated aldosterone release; when the decrease in pH was minimized, CO2 inhibited ANG II-stimulated aldosterone release. Hypoxia inhibited aldosterone release; the inhibitory effect of hypoxia predominated when combined with CO2. In the presence of cyanoketone, pregnenolone production from endogenous precursors (early pathway) was unaffected. However, the conversion of corticosterone to aldosterone (late pathway) was inhibited by low O2 but unaffected by CO2. It is concluded that the inhibitory effect of low O2 on the late pathway predominates over the effects of uncompensated or compensated simulated respiratory acidosis on aldosteronogenesis.

SECRETION OF PROGESTERONE BY HUMAN OVARIES PERFUSED IN VITRO

1975 ◽  
Vol 79 (1) ◽  
pp. 111-121 ◽  
Author(s):  
H. Fukunishi ◽  
H. Mickan ◽  
J. Zander
Keyword(s):  
Ovarian Function ◽  
Sodium Lactate ◽  
Bicarbonate Buffer ◽  
Ldh Activity ◽  
Progesterone Secretion ◽  
Experimental Approaches ◽  
Lactate And Pyruvate ◽  
Human Ovaries

ABSTRACT A system for the perfusion of isolated human ovaries is described. Krebs-Ringer bicarbonate buffer (pH 7.4) containing glucose, sodium lactate and pyruvate was perfused at a flow rate of 5–8 ml/min at 37°C through the ovarian artery. Oxygen uptake, LDH-activity, pH and progesterone secretion were determined as parameters of viability of the perfused organ. Our results demonstrate that a relatively simple system used for perfusion was able to preserve ovarian function for at least two hours. This experimental design should not be regarded as physiological but in addition to other experimental approaches it might provide information on the physiology of the human ovary. Though lower values of progesterone secretion than in vivo were found, a correlation of secretion and functional stage of the ovaries could be demonstrated.

Glycogenolysis in the Anoxic Heart

1956 ◽  
Vol 186 (3) ◽  
pp. 518-520 ◽  
Author(s):  
Walter L. Bloom
Keyword(s):  
Critical Factor ◽  
Work Load ◽  
Glycogen Depletion ◽  
Cardiac Work ◽  
Open Chest ◽  
Heart Beating ◽  
Large Vessels ◽  
Intact Rats

It has been generally accepted that cardiac anoxia caused glycogen depletion and epinephrine was implicated as a mediator in this glycogenolysis. Recently, work has shown that epinephrine and norepinephrine produce an increase in cardiac glycogen rather than glycogen depletion in the rat. Since cardiac work was not considered in previous studies, the present experiment was designed to test the effect of work on glycogenolysis of the anoxic heart in vivo and in vitro. Unfasted rats were anesthetized and observations were made on intact rats with anoxia resulting from an open chest. In vitro studies were performed on rapidly excised hearts studied in room air, in saline and in nitrogen. After 4 minutes of anoxia in the open chest 83% of the control glycogen was lost and no difference was noted whether or not the adrenal medullae were present. When the large vessels were severed, much less glycogenolysis occurred in the anoxic heart. No glycogen decrease was observed in the excised heart beating 4 minutes in room air or in nitrogen, but significant glycogenolysis was observed in the anoxic heart beating 4 minutes in saline. The anoxic heart severed from the circulation has shown no glycogenolysis whereas the anoxic heart with intact circulation showed marked glycogenolysis. It would appear from this experiment that anoxia per se was not the cause of glycogen decrease but that the amount of work performed by the anoxic heart was the critical factor in producing glycogenolysis. When a work load was placed on the excised heart beating in saline, glycogen decrease was observed. Epinephrine has been excluded as the cause of glycogenolysis in the anoxic heart since comparable cardiac glycogen changes were observed during anoxia in normal and adrenal demedullated rats.

Antiketogenic effect of glucose per se in vivo in man and in vitro in isolated rat liver cells

Metabolism ◽  
1986 ◽  
Vol 35 (7) ◽  
pp. 608-613 ◽  
Author(s):  
J.P. Riou ◽  
M. Beylot ◽  
M. Laville ◽  
L. De Parscau ◽  
J. Delinger ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Cells ◽  
Isolated Rat Liver ◽  
Rat Liver Cells ◽  
Per Se ◽  
Effect Of Glucose ◽  
Isolated Rat

scholarly journals Effects of dichloroacetate on the metabolism of glucose, pyruvate, acetate, 3-hydroxybutyrate and palmitate in rat diaphragm and heart muscle in vitro and on extraction of glucose, lactate, pyruvate and free fatty acids by dog heart in vivo

1973 ◽  
Vol 134 (4) ◽  
pp. 1067-1081 ◽  
Author(s):  
Anthony McAllister ◽  
S. P. Allison ◽  
Philip J. Randle
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Plasma Free Fatty Acid ◽  
Diabetic Rats ◽  
Inhibitory Effects ◽  
Acetyl Coa ◽  
Citrate Concentration ◽  
Lactate And Pyruvate

1. The extractions of glucose, lactate, pyruvate and free fatty acids by dog heart in vivo were calculated from measurements of their arterial and coronary sinus blood concentration. Elevation of plasma free fatty acid concentrations by infusion of intralipid and heparin resulted in increased extraction of free fatty acids and diminished extractions of glucose, lactate and pyruvate by the heart. It is suggested that metabolism of free fatty acids by the heart in vivo, as in vitro, may impair utilization of these substrates. These effects of elevated plasma free fatty acid concentrations on extractions by the heart in vivo were reversed by injection of dichloroacetate, which also improved extraction of lactate and pyruvate by the heart in vivo in alloxan diabetes. 2. Sodium dichloroacetate increased glucose oxidation and pyruvate oxidation in hearts from fed normal or alloxan-diabetic rats perfused with glucose and insulin. Dichloroacetate inhibited oxidation of acetate and 3-hydroxybutyrate and partially reversed inhibitory effects of these substrates on the oxidation of glucose. In rat diaphragm muscle dichloroacetate inhibited oxidation of acetate, 3-hydroxybutyrate and palmitate and increased glucose oxidation and pyruvate oxidation in diaphragms from alloxan-diabetic rats. Dichloroacetate increased the rate of glycolysis in hearts perfused with glucose, insulin and acetate and evidence is given that this results from a lowering of the citrate concentration within the cell, with a consequent activation of phosphofructokinase. 3. In hearts from normal rats perfused with glucose and insulin, dichloroacetate increased cell concentrations of acetyl-CoA, acetylcarnitine and glutamate and lowered those of aspartate and malate. In perfusions with glucose, insulin and acetate, dichloroacetate lowered the cell citrate concentration without lowering the acetyl-CoA or acetylcarnitine concentrations. Measurements of specific radioactivities of acetyl-CoA, acetylcarnitine and citrate in perfusions with [1-14C]acetate indicated that dichloroacetate lowered the specific radio-activity of these substrates in the perfused heart. Evidence is given that dichloroacetate may not be metabolized by the heart to dichloroacetyl-CoA or dichloroacetylcarnitine or citrate or CO2. 4. We suggest that dichloroacetate may activate pyruvate dehydrogenase, thus increasing the oxidation of pyruvate to acetyl-CoA and acetylcarnitine and the conversion of acetyl-CoA into glutamate, with consumption of aspartate and malate. Possible mechanisms for the changes in cell citrate concentration and for inhibitory effects of dichloroacetate on the oxidation of acetate, 3-hydroxybutyrate and palmitate are discussed.

Accelerated glycogenolysis in uremia and under sucrose feeding: role of phosphorylase alpha regulators

1997 ◽  
Vol 273 (1) ◽  
pp. E17-E27
Author(s):  
Z. Bakkour ◽  
D. Laouari ◽  
S. Dautrey ◽  
J. P. Yvert ◽  
C. Kleinknecht
Keyword(s):  
Hepatic Glucose Production ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Glycogen Storage ◽  
Hepatic Insulin Resistance ◽  
Hepatic Glycogen ◽  
Glycogen Depletion ◽  
Sucrose Feeding

To understand the mechanism of hepatic glycogen depletion found in uremia and under sucrose feeding, we examined net hepatic glycogenolysis-associated active enzymes and metabolites during fasting. Liver was taken 2, 7, and 18 h after food removal in uremic and pair-fed control rats fed either a sucrose or cornstarch diet for 21 days. Other uremic and control rats fasted for 18 h were refed a sucrose meal to measure glycogen increment. Glycogen storage in uremia was normal, suggesting effective glycogen synthesis. During a short fast, sucrose feeding and uremia enhanced net glycogenolysis through different but additive mechanisms. Under sucrose feeding, there were high phosphorylase alpha levels associated with hepatic insulin resistance. In uremia, phosphorylase alpha levels were low, but the enzyme was probably activated in vivo by a fall of inhibitors (ATP, alpha-glycerophosphate, fructose-1,6-diphosphate, and glucose) and a rise of Pi, as verified in vitro. Enhanced gluconeogenesis was also suggested, but excessive hepatic glucose production was unlikely in uremia. During fasting, hypoglycemia occurred in uremia due to reduced glycogenolysis, inefficient hepatic gluconeogenesis, and impaired renal gluconeogenesis. This may be relevant to poor fasting tolerance in uremia, which could be aggravated under excessive sucrose intake.

Fatty Acid Utilization by Adrenalectomized Rats

1956 ◽  
Vol 186 (2) ◽  
pp. 190-192 ◽  
Author(s):  
W. F. Perry ◽  
Helen F. Bowen
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Octanoic Acid ◽  
Hepatic Lipogenesis ◽  
Acetoacetic Acid ◽  
Fatty Acid Utilization ◽  
Liver Slices ◽  
Adrenalectomized Rats

The production of radioactive CO2 by intact and adrenalectomized rats given 1 C14 octanoic acid and the production of radioactive CO2 and radioactive acetoacetic acid by surviving liver slices from adrenalectomized and unoperated rats using 1 C14 octanoic acid as substrate have been studied. It was found that the CO2 production and acetoacetic acid production in vitro and CO2 production in vivo did not differ in the two types of animals. These results suggest that the adrenalectomized rat does not utilize fatty acids at a higher than normal rate and that the previously reported decreased incorporation of acetate into fatty acids by the liver slices from adrenalectomized rats is a reflection of decreased hepatic lipogenesis.

scholarly journals Rapid inhibition of lipogenesis in vivo in lactating rat mammary gland by medium- or long-chain triacylglycerols and partial reversal by insulin

1980 ◽  
Vol 192 (1) ◽  
pp. 361-364 ◽  
Author(s):  
L Agius ◽  
D H Williamson
Keyword(s):  
Mammary Gland ◽  
Glucose Utilization ◽  
Insulin Administration ◽  
Hepatic Lipogenesis ◽  
Medium Chain ◽  
Rat Mammary Gland ◽  
Long Chain ◽  
Partial Reversal

An intragastric load of medium- or long-chain triacylglycerols inhibited lipogenesis in lactating rat mammary gland in vivo by 82 or 89% respectively. This inhibition was reversed partially by insulin administration. Long-chain triacylglycerols inhibited hepatic lipogenesis in vivo but medium-chain triacylglycerols increased it 2-fold. Glucose utilization in vitro by mammary gland acini from triacylglycerol-fed rat was normal.

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