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.

Reduced Prostacyclin Survival After Fasting-Induced Elevation of Plasma Free Fatty Acids

1985 ◽  
Vol 54 (02) ◽  
pp. 418-421 ◽  
Author(s):  
S H Goodnight ◽  
S B Inkeles ◽  
N L Kovach ◽  
W E Connor
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Platelet Reactivity ◽  
Plasma Free Fatty Acid ◽  
Vascular Wall ◽  
Functional Assay ◽  
Ratio Test ◽  
Platelet Aggregate

SummaryThe anti-thrombotic effect of prostacyclin (PGI2) may be determined not only by its synthetic rate but also by its subsequent survival in blood. After its release from the vascular wall, prostacyclin binds to plasma albumin which stabilizes the molecule and prolongs its inhibitory effects on platelets. In vitro studies have shown that free fatty acids compete for the same albumin binding sites and may therefore displace PGI2 and substantially shorten its survival. To see if this competition could also occur in vivo, we produced a three-fold rise of plasma free fatty acid concentrations in ten normal volunteers by four days of fasting, which led to a significant reduction in prostacyclin survival as measured by a functional assay based on inhibition of ADP-induced platelet aggregation. The shortening of prostacyclin survival was associated with evidence of increased platelet reactivity as measured by the circulating platelet aggregate ratio test. Diseases that produce marked elevations of free fatty acids such as acute myocardial infarction may also lead to shortened PGI2 survival with potentiation of platelet mediated thrombosis.

Lowering of plasma glucose in diabetic rats by antilipolytic agents

1988 ◽  
Vol 254 (1) ◽  
pp. E23-E30 ◽  
Author(s):  
G. M. Reaven ◽  
H. Chang ◽  
H. Ho ◽  
C. Y. Jeng ◽  
B. B. Hoffman
Keyword(s):  
Glucose Uptake ◽  
Plasma Glucose ◽  
Plasma Free Fatty Acid ◽  
Diabetic Rats ◽  
Plasma Insulin Concentration ◽  
Glucose Response ◽  
Adenosine Receptor Agonist ◽  
Lower Plasma Glucose

Both nicotinic acid (NA) and the adenosine receptor agonist phenylisopropyladenosine (PIA) are potent antilipolytic agents. We have evaluated the ability of these compounds to lower plasma glucose concentration in 450-g male diabetic rats. Diabetes was induced by intravenous streptozotocin, and the rats were studied 7-10 days later. Mean (+/- SE) fasting glucose decreased 4 h after subcutaneous injections of PIA at 0 and 2 h. A similar change in plasma glucose level was also seen in rats injected with NA. The decrease in the concentration of plasma glucose in both instances was preceded by marked sustained reductions in plasma free fatty acid (FFA) concentrations; FFA decreased in PIA-injected rats and in response to NA. With injection of normal saline, neither plasma glucose nor FFA concentrations decreased in diabetic rats. There was no change in the plasma insulin concentration of rats that had hypoglycemic responses to PIA or NA. In vitro glucose uptake was determined in isolated adipocytes, and both PIA and NA were shown to increase basal and maximal insulin-stimulated glucose uptake. The stimulating effect of the two compounds was similar, and the magnitude of the effect was comparable in adipocytes from either normal or diabetic rats. As a result, neither NA nor PIA could restore the defects in glucose transport to normal in adipocytes from diabetic rats. Insulin-stimulated glucose uptake was assessed in vivo by determining the steady-state glucose response of diabetic rats to a continuous infusion of insulin and glucose and was found to be significantly enhanced in response to NA compared with NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid Labelling in Intact Chloroplasts from Exogenous Nucleotide Precursors

1981 ◽  
Vol 36 (1-2) ◽  
pp. 62-70 ◽  
Author(s):  
Margrit Bertrams ◽  
Käthe Wrage ◽  
Ernst Heinz
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
De Novo ◽  
Membrane System ◽  
Chloroplast Envelope ◽  
Label Free ◽  
Intact Chloroplasts ◽  
Time Required

Abstract De novo-synthesis of glycerolipids in chloroplasts is initiated by a stroma enzyme which catalyzes the formation of lyso-phosphatidic acid from glycerophosphate and acyl-CoA. When these substrates are added to isolated, intact chloroplasts, only glycerophosphate can readily pass through the chloroplast envelope which represents a permeation barrier for acyl-CoA, although higher thioester concentrations destroy this membrane system. At low concentrations of acyl-CoA, which do not impair the envelope, intact chloroplasts metabolize exogenous acyl-CoA in two ways to give free fatty acids and labelled phosphatidyl choline. This indicates that the envelope thioesterase can use exogenous substrates. Isolated, intact chloroplasts fixing radioactive CO2 label free fatty acids and acylglycerols but not galactolipids, since they cannot convert 3-phosphoglycerate into UDP-galactose which in vivo is supplied by the cytoplasm. This cooperation was simulated in vitro by adding all enzymes and cofactors necessary for conversion of 3-phosphoglycerate into UDP-galactose to intact chloro­plasts which then formed labelled monogalactosyl diacylglycerol from labelled CO2. The time required to transfer envelope-made galactolipids from the envelope into thylakoids was studied by incubating intact chloroplasts with radioactive UDP-galactose, subsequent osmotic disruption of organelles with concomitant enzymatic degradation of UDP-galactose followed by separation of envelopes and thylakoids. Only after short times (< 1min) appreciable proportions 920-30%) of radioactive galactolipid export from envelopes into thylakoids.

2,5-anhydro-D-mannitol: a fructose analogue that increases food intake in rats

1988 ◽  
Vol 254 (1) ◽  
pp. R150-R153 ◽  
Author(s):  
M. G. Tordoff ◽  
R. Rafka ◽  
M. J. DiNovi ◽  
M. I. Friedman
Keyword(s):  
Fatty Acids ◽  
Food Intake ◽  
Free Fatty Acids ◽  
Plasma Glucose ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Substrate Analogues ◽  
Increase Food Intake ◽  
Related Increase

We examined the effects on food intake and plasma fuels of 2,5-anhydro-D-mannitol (2,5-AM; 2-deoxy-D-fructose), a fructose analogue that inhibits hepatocyte gluconeogenesis and glycogenolysis in vitro. 2,5-AM (50-800 mg/kg po) given to rats during the diurnal fast produced a dose-related increase in food intake during the 2 h after administration. A 200-mg/kg dose of 2,5-AM decreased plasma glucose, increased plasma ketone bodies, free fatty acids, and glycerol, and had no effect on triglycerides. Normal and diabetic rats given 2,5-AM (200 mg/kg ip) increased food intake to the same extent. These results suggest that, unlike other substrate analogues that increase food intake, 2,5-AM increases feeding by creating a metabolic state that resembles fasting.

THE STIMULATING EFFECTS OF ADRENALINE AND ANTERIOR PITUITARY HORMONES ON THE RELEASE OF FREE FATTY ACIDS FROM ADIPOSE TISSUE

1962 ◽  
Vol 25 (2) ◽  
pp. 189-198 ◽  
Author(s):  
R. M. BUCKLE
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Pituitary Hormones ◽  
Thyroid Stimulating Hormone ◽  
Adrenocorticotrophic Hormone ◽  
Fat Pads

SUMMARY The quantity of free fatty acids (FFA) released from rat epididymal fat pads in vitro and their concentration within the tissue were determined. The addition of adrenaline, adrenocorticotrophic hormone (ACTH), thyroid stimulating hormone (TSH) and growth hormone (GH) each increased the release of FFA, and their respective minimum effective concentrations were 0·125, 0·004, 0·5 and 1·25 μg./ml. of medium. In every case, the increased release of FFA was associated with a rise in the quantity present within the pads, and the amount released closely paralleled their concentration within the tissue. It is suggested that the stimulatory effect of all four hormones on the release of FFA from adipose tissue is largely a manifestation of their activity of increasing the concentration of FFA within the cells, and this they do by facilitating the net conversion of storage triglyceride to fatty acid. The significance of the relative activities of the hormones in vitro is discussed and compared with their fatty acid mobilizing effects in vivo.

scholarly journals Elevated free fatty acids affect bovine granulosa cell function: a molecular cue for compromised reproduction during negative energy balance

2019 ◽  
Vol 8 (5) ◽  
pp. 493-505 ◽  
Author(s):  
Arpna Sharma ◽  
Vijay Simha Baddela ◽  
Frank Becker ◽  
Dirk Dannenberger ◽  
Torsten Viergutz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Energy Balance ◽  
Free Fatty Acids ◽  
Dairy Cows ◽  
Combination Treatment ◽  
Follicular Fluid ◽  
Negative Energy

High-yielding dairy cows postpartum face the challenge of negative energy balance leading to elevated free fatty acids levels in the serum and follicular fluid thus affecting the ovarian function. Here, we investigated effects of physiological concentrations of palmitic acid (PA), stearic acid (SA) and oleic acid (OA) on the viability, steroid production and gene expression in a bovine granulosa cell (GC) culture model. Treatment with individual and combined fatty acids increased the CD36 gene expression, while no significant apoptotic effects were observed. Both PA and SA significantly upregulated the expression of FSHR, LHCGR, CYP19A1, HSD3B1, CCND2 and increased 17β-estradiol (E2) production, while OA downregulated the expression of these genes and reduced E2. Interestingly, STAR was equally downregulated by all fatty acids and combination treatment. E2 was significantly reduced after combination treatment. To validate the effects of OA, in vivo growing dominant follicles (10–19 mm) were injected with bovine serum albumin (BSA) with/without conjugated OA. The follicular fluid was recovered 48 h post injection. As in our in vitro model, OA significantly reduced intrafollicular E2 concentrations. In addition, expression of CD36 was significantly up- and that of CYP19A1 and STAR significantly downregulated in antral GC recovered from aspirated follicles. The ovulation rates of OA-injected follicles tended to be reduced. Our results indicate that elevated free fatty acid concentrations specifically target functional key genes in GC both in vitro and in vivo. Suggestively, this could be a possible mechanism through which elevated free fatty acids affect folliculogenesis in dairy cows postpartum.

scholarly journals Studies on lipid digestion in the preruminant calf

1978 ◽  
Vol 40 (1) ◽  
pp. 125-131 ◽  
Author(s):  
J. D. Edwards-Webb ◽  
S. Y. Thompson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Butyric Acid ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Esterified Fatty Acids ◽  
Chain Fatty Acids

1. The lipolysis of cow's milk fat by salivary lipase (EC 3.1.1.3) in the preruminant calf has been studied in vitro by a simulated abomasal digestion, and also in vivo by examining the abomasal effluent collected over 12 h after giving whole milk to a calf.2. In the in vitro experiment the liquid drained from the clot contained a higher proportion of short-chain fatty acids than the abomasal effluent in the in vivo experiment. This was considered to indicate the absorption of short-chain free fatty acids from within the abomasum.3. Preferential release of short-chain fatty acids both in vitro and in vivo was observed.4. The outflow of butyric acid from the abomasum of the calf was initially rapid, but had levelled off at approximately 6 h, whereas the outflow of a typical long-chain fatty acid (palmitic) was fairly constant over the 12 h.Butyric acid predominated in the free fatty acids of abomasal effluent 0.5 h after feeding (668 mmol/mol total free fatty acids) but had become a minor component by 12 h (15 mmol/mol total free fatty acids).5. The mean amounts of free and esterified fatty acids (mmol/mol fatty acid ingested) present in the abomasal effluent from the 12 h collection period were: triglyceride 465, diglyceride 215, monoglyceride 68, free fatty acid 252. These values showed that only one-third of esterified fatty acids ingested are lipolysed to absorbable products by salivary lipase.

In vitro and in vivo effects of increased concentrations of free fatty acids on free thyroxin measurements as determined by five assays

1990 ◽  
Vol 36 (4) ◽  
pp. 611-613 ◽  
Author(s):  
R Sapin ◽  
J L Schlienger ◽  
F Grunenberger ◽  
F Gasser ◽  
J Chambron
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
The Other ◽  
In Vitro Experiments ◽  
Fat Emulsion ◽  
Before And After ◽  
High Concentrations ◽  
In Vivo Effects

Abstract To compare in vitro and in vivo effects of increased concentrations of free fatty acids (FFA) on free thyroxin (FT4) values, we measured FT4 in three pooled sera supplemented with oleate and in serum from 18 euthyroid patients before and after an infusion of fat emulsion (Intralipid). We used five FT4 RIA kits: two two-step methods [Gammacoat, Baxter (GC); Ria-gnost, Behring (RG)], two analog RIAs [Amerlex-M, Amersham (AM); Coat-Ria, BioMérieux (CR)], and one kit with labeled antibodies [Amerlex-MAB*, Amersham (AA)]. In vitro, at the maximum oleate addition of 5 mmol/L, FT4 increased when measured by the GC and RG kits, decreased by the AM kit, and showed no significant change by the CR and AA kits. In vivo, post-Intralipid, FFA concentrations rose significantly and the FT4 changes agreed with the results of the in vitro experiments, except for the RG kit, for which FT4 increased in only nine patients. We conclude that in vitro oleate addition is useful to predict the in vivo effect of increased FFA on FT4 values; moreover, in serum from euthyroid subjects with high concentrations of FFA, FT4 analyzed with the CR or AA kits should better agree with normal results for thyrotropin than FT4 values measured with the other kits.

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