Platelet-activating factor causes hypoketonaemia in starved rats

1992 ◽  
Vol 83 (4) ◽  
pp. 495-501
Author(s):  
Atsushi Hiraide ◽  
Rhys D. Evans ◽  
Dermot H. Williamson

1. The aim of this work was to examine whether platelet-activating factor could mimic the hypoketonaemia seen in septic and endotoxic experimental animals. Platelet-activating factor was administered either by the intraperitoneal (high dose) or intravenous (jugular vein, low dose) routes. 2. Intraperitoneal injection of platelet-activating factor (25 μg/kg body weight) decreased the blood ketone body concentration (acetoacetate plus 3-hydroxybutyrate) transiently (30 min after injection) in starved rats. Continuous intravenous infusion of platelet-activating factor (40 ng min−1 kg−1 for 5 h) caused comparable hypoketonaemia. 3. The hepatic acetoacetate concentration also decreased transiently after injection of platelet-activating factor and there was an increase in the 3-hydroxybutyrate/acetoacetate ratio. The hepatic ATP concentration decreased at 15 and 30 min after injection of platelet-activating factor. Infusion of platelet-activating factor caused a similar decrease in hepatic ketone body concentration, but no significant change in the 3-hydroxybutyrate/acetoacetate ratio or adenine nucleotide concentrations. 4. Platelet-activating factor administered by infusion, but not by injection, decreased the plasma non-esterified fatty acid concentration. The plasma glycerol concentration also decreased after infusion of platelet-activating factor, suggesting decreased lipolysis in adipose tissue. 5. Changes in plasma insulin concentration or white adipose tissue blood flow did not appear to contribute to the decrease in the plasma non-esterified fatty acid concentration after infusion of platelet-activating factor. However, there was a significant decrease in blood flow to interscapular brown adipose tissue in both the infused and injected groups. 6. These findings suggest that infusion of platelet-activating factor causes a decrease in ketone bodies by limiting the supply of non-esterified fatty acids to the liver, and that the transient hypoketonaemia seen with intraperitoneal injection may possibly be due to decreased oxidation of non-esterified fatty acids secondary to hepatic vasoconstriction.

1976 ◽  
Vol 51 (1) ◽  
pp. 107-110 ◽  
Author(s):  
N. E. Miller ◽  
O. D. Mjøs ◽  
M. F. Oliver

1. The mechanism whereby p-chlorophenoxyisobutyrate (CPIB) lowers plasma non-esterified fatty acid concentrations has been studied in dogs by measuring the associated changes in adipose tissue metabolism. 2. CPIB lowered arterial concentrations of non-esterified fatty acids during isoprenaline infusion by a mean value of 41%. 3. This was accompanied by a proportionate decrease (45%) in the release of non-esterified fatty acids from subcutaneous adipose tissue in situ, and by a lesser reduction (22%) in that of glycerol. 4. Adipose tissue blood flow was unchanged by CPIB. 5. These findings indicate that the lowering effect of CPIB on non-esterified fatty acid concentrations derives principally from decreased mobilization rather than from increased tissue uptake of the fatty acids, and that this reflects both inhibited lipolysis and enhanced re-esterification of the fatty acids in adipose tissue.


1983 ◽  
Vol 50 (1) ◽  
pp. 81-89 ◽  
Author(s):  
J. A. Bines ◽  
S. V. Morant

1. Changes in concentrations of metabolites in blood and rumen fluid were measured in cows when fat and when thin and when given hay and concentrates at a restricted level or ad lib.2. When fed ad lib., cows consumed 24% more food when thin than when fat.3. Concentrations in rumen fluid of acetate and propionate after feeding at both levels did not differ significantly between fat and thin cows.4. Concentrations in blood of the lipogenic substrates acetate and 3-hydroxybutyrate did not differ between fat and thin cows after feeding, but glucose concentration fell more rapidly in thin cows especially when fed ad lib. Propionate rose more in thin cows than in fat cows when fed ad lib. Non-esterified fatty acids were higher in fat cows before feeding, but fell to similar levels to those in thin cows after feeding.5. The results are interpreted as indicating a more rapid rate of fatty acid synthesis in adipose tissue of thin cows. This in turn tends to lower blood levels of fatty acid precursors and so enhance the rate of their absorption from the rumen. This in turn permits higher intake of food before short-term chemical regulators of intake start to operate.


1971 ◽  
Vol 40 (6) ◽  
pp. 463-477 ◽  
Author(s):  
R. N. Barton

1. The effect of a 4 h period of bilateral hind limb ischaemia on the concentrations of ketone bodies in blood and liver of post-absorptive and starved rats has been investigated. 2. The concentration of total ketone bodies in the blood did not change after injury in post-absorptive rats, but fell after injury in starved rats; the blood β-hydroxybutyrate/acetoacetate ratio fell after injury in both post-absorptive and starved rats. 3. Apart from a transient increase in fed rats, the hepatic β-hydroxybutyrate/acetoacetate ratio did not change after injury in post-absorptive or starved rats until the terminal stages, indicating adequate hepatic oxygenation during the early response to injury. 4. In control post-absorptive and starved rats the concentration of liver total ketone bodies was correlated with that of plasma non-esterified fatty acids; in post-absorptive rats the liver ketone body concentration rose after injury and was higher than would be predicted from the regression line for these controls, suggesting increased ketogenesis compatible with inhibition of complete oxidation of non-esterified fatty acids after injury. In contrast, in starved rats the liver total ketone-body concentration did not change after injury.


1968 ◽  
Vol 106 (3) ◽  
pp. 677-682 ◽  
Author(s):  
Sheila Otway ◽  
D S Robinson

1. The concentration of triglyceride fatty acid in the plasma of the pregnant rat rises to a maximum 2–4 days before parturition. Thereafter there is a rapid decline in the concentration to near normal values at parturition. 2. A similar increase occurs in animals fed on a diet low in fat. There is no increase in food consumption at the time when the triglyceride fatty acid concentration in the plasma is at its peak. 3. Rates of entry of triglyceride fatty acid into the blood during pregnancy have been estimated from the rate of accumulation of triglyceride in the plasma of animals injected with a non-ionic detergent, Triton. A progressive increase occurs in the entry rate as the body weight increases throughout pregnancy. Expressed per constant body weight, the entry rate does not change significantly. 4. Adipose-tissue clearing-factor lipase activity is low at the time when the plasma triglyceride fatty acid concentration is raised. Activity of the enzyme in heart, lung and diaphragm is unchanged. 5. It is suggested that the ‘lipaemia of pregnancy’ may be due to diminished uptake of triglyceride fatty acids by adipose tissue, and, further, that the disappearance of the lipaemia may be due to increased uptake of triglyceride fatty acids by the mammary gland.


1994 ◽  
Vol 86 (2) ◽  
pp. 177-184 ◽  
Author(s):  
A. Kurpad ◽  
K. Khan ◽  
A. G. Calder ◽  
S. Coppack ◽  
K. Frayn ◽  
...  

1. The effect of infusion of noradrenaline (0.42 μmol min−1 kg−1) on the exchange of non-esterified fatty acids, glycerol and other metabolites across subcutaneous abdominal adipose tissue was investigated in five healthy subjects using an arteriovenous catheterization technique and measurement of adipose tissue blood flow using the 133Xe clearance technique. At the same time, the net rate of fat oxidation in the whole body was assessed by indirect calorimetry, and the turnover of glycerol in the whole body and in subcutaneous adipose tissue was estimated using [5-2H]glycerol, which was administered as a primed constant infusion for 1 h before (basal turnover) noradrenaline administration and continued during the 1 h of noradrenaline infusion. 2. The noradrenaline infusion increased the plasma noradrenaline concentration from a basal value of 0.9 ± 0.1 to 12.6 ± 1.2 nmol/(mean ± SEM) at 60 min. It also increased the arterialized concentration of glycerol by 50% (basal value 81 ± 11/μmol/l−1) and that of plasma non-esterified fatty acids three-fold (basal value 357 ± 86 μmol/l). 3. Noradrenaline increased the net release of glycerol by adipose tissue three-fold and that of non-esterified fatty acids three- to four-fold. Although the ratio of non-esterified fatty acid to glycerol release by adipose tissue increased in all subjects from a mean value of 2.7 in the basal period to 3.6 and 3.9 at 50 and 60 min of the noradrenaline infusion, respectively (P < 0.02), at no time point did the ratio differ significantly from 3.0 4. Noradrenaline increased the estimated rate of appearance of glycerol in the whole body from a basal value of 1.5 ± 0.3 to 2.6 ± 0.3 μmol min−1 kg−1 body weight, and the net rate of triacylglycerol oxidation from 1.2 ± 0.1 to 1.7 ± 0.13 μmol min−1 kg−1. The enrichment of glycerol in venous blood draining adipose tissue was two-fold lower than that predicted from the net addition of glycerol to the blood in the basal period (P < 0.02). 5. This study provides a direct demonstration of a ‘hormone’ stimulating lipolysis in human adipose tissue in viva The effect of noradrenaline in significantly increasing the ratio of non-esterified fatty acid to glycerol release by adipose tissue may be partly explained by accumulation in adipose tissue of diacylglycerol, which is associated with release of non-esterified fatty acids but not glycerol. Finally, since the low enrichment of glycerol in venous blood draining adipose tissue cannot be entirely explained by the net addition of glycerol in adipose tissue, there must be exchange between enriched glycerol in blood and unenriched glycerol in adipose tissue. This raises questions about the accuracy of glycerol turnover studies, which are typically carried out over 1 h.


1985 ◽  
Vol 54 (03) ◽  
pp. 563-569 ◽  
Author(s):  
M K Salo ◽  
E Vartiainen ◽  
P Puska ◽  
T Nikkari

SummaryPlatelet aggregation and its relation to fatty acid composition of platelets, plasma and adipose tissue was determined in 196 randomly selected, free-living, 40-49-year-old men in two regions of Finland (east and southwest) with a nearly twofold difference in the IHD rate.There were no significant east-southwest differences in platelet aggregation induced with ADP, thrombin or epinephrine. ADP-induced platelet secondary aggregation showed significant negative associations with all C20-C22 ω3-fatty acids in platelets (r = -0.26 - -0.40) and with the platelet 20: 5ω3/20: 4ω 6 and ω3/ ω6 ratios, but significant positive correlations with the contents of 18:2 in adipose tissue (r = 0.20) and plasma triglycerides (TG) (r = 0.29). Epinephrine-induced aggregation correlated negatively with 20: 5ω 3 in plasma cholesteryl esters (CE) (r = -0.23) and TG (r = -0.29), and positively with the total percentage of saturated fatty acids in platelets (r = 0.33), but had no significant correlations with any of the ω6-fatty acids. Thrombin-induced aggregation correlated negatively with the ω3/6ω ratio in adipose tissue (r = -0.25) and the 20: 3ω6/20: 4ω 6 ratio in plasma CE (r = -0.27) and free fatty acids (FFA) (r = -0.23), and positively with adipose tissue 18:2 (r = 0.23) and 20:4ω6 (r = 0.22) in plasma phospholipids (PL).The percentages of prostanoid precursors in platelet lipids, i. e. 20: 3ω 6, 20: 4ω 6 and 20 :5ω 3, correlated best with the same fatty acids in plasma CE (r = 0.32 - 0.77) and PL (r = 0.28 - 0.74). Platelet 20: 5ω 3 had highly significant negative correlations with the percentage of 18:2 in adipose tissue and all plasma lipid fractions (r = -0.35 - -0.44).These results suggest that, among a free-living population, relatively small changes in the fatty acid composition of plasma and platelets may be reflected in significant differences in platelet aggregation, and that an increase in linoleate-rich vegetable fat in the diet may not affect platelet function favourably unless it is accompanied by an adequate supply of ω3 fatty acids.


2020 ◽  
Vol 19 (2) ◽  
pp. 217-221
Author(s):  
Maria Jesús Lisbona-González ◽  
Candela Reyes-Botella ◽  
Esther Muñoz-Soto ◽  
Maria Victoria Olmedo-Gaya, ◽  
Jorge Moreno-Fernandez ◽  
...  

Adipose tissue is an endocrine organ and has central role in interaction with other organs or tissues while propolis can induce lipolysis. Therefore, the aim of this study is to provide detailed information about adipose tissue homeostasis modifications and body composition during propolis supplement consumption. Twenty male Wistar albino rats (8 weeks) were divided into two groups of 10 animals each and fed for 90 days with two different types of diets: standard for the control group (diet C) and standard diet + 2% propolis (diet P). Thyroid hormones did not show differences, while ghrelin and adiponectin decreased in the group that was fed propolis. Insulin, leptin, and non-esterified fatty acids also increased along with reduced body weight and fat, in addition to increased lean mass when propolis was in the diet. We conclude that propolis could decrease ghrelin and adiponectin but increase non-esterified fatty acids and insulin secretion, which improves body composition.


1961 ◽  
Vol 200 (4) ◽  
pp. 847-850 ◽  
Author(s):  
Judith K. Patkin ◽  
E. J. Masoro

Cold acclimation is known to alter hepatic lipid metabolism. Liver slices from cold-acclimated rats have a greatly depressed capacity to synthesize long-chain fatty acids from acctate-1-C14. Since adipose tissue is the major site of lipogenic activity in the intact animal, its fatty acid synthetic capacity was studied. In contrast to the liver, it was found that adipose tissue from the cold-acclimated rat synthesized three to six times as much long-chain fatty acids per milligram of tissue protein as the adipose tissue from the control rat living at 25°C. Evidence is presented indicating that adipose tissue from cold-acclimated and control rats esterify long-chain fatty acids at the same rate. The ability of adipose tissue to oxidize palmitic acid to CO2 was found to be unaltered by cold acclimation. The fate of the large amount of fatty acid synthesized in the adipose tissue of cold-acclimated rats is discussed.


1988 ◽  
Vol 250 (3) ◽  
pp. 819-825 ◽  
Author(s):  
E P Brass ◽  
R A Beyerinck

Accumulation of propionate, or its metabolic product propionyl-CoA, can disrupt normal cellular metabolism. The present study examined the effects of propionate, or propionyl-CoA generated during the oxidation of odd-chain-length fatty acids, on hepatic oxidation of short- and medium-chain-length fatty acids. In isolated hepatocytes, ketone-body formation from odd-chain-length fatty acids was slow as compared with even-chain-length fatty acid substrates, and increased as the carbon chain length was increased from five to seven to nine. In contrast, rates of ketogenesis from butyrate, hexonoate and octanoate were all approximately equal. Propionate (10 mM) inhibited ketogenesis from butyrate, hexanoate and octanoate by 81%, 53% and 18% respectively. Addition of carnitine had no effect on ketogenesis from the even-chain-length fatty acids, but increased the rate of ketone-body formation from pentanoate (by 53%), heptanoate (by 28%) and from butyrate or hexanoate in the presence of propionate. The inhibitory effect of propionate could not be explained by shunting acetyl-CoA into the tricarboxylic acid cycle, as CO2 formation from butyrate was also decreased by propionate. Examination of the hepatocyte CoA pool during oxidation of butyrate demonstrated that addition of propionate decreased acetyl-CoA and CoA as propionyl-CoA accumulated. Addition of carnitine decreased propionyl-CoA by 50% (associated with production of propionylcarnitine) and increased acetyl-CoA and CoA. Similar changes in the CoA pool were seen during the oxidation of pentanoate. These results demonstrate that accumulation of propionyl-CoA results in inhibition of short-chain fatty acid oxidation. Carnitine can partially reverse this inhibition. Changes in the hepatocyte CoA pool are consistent with carnitine acting by generating propionylcarnitine, thereby decreasing propionyl-CoA and increasing availability of free CoA. The data provide further evidence of the potential cellular toxicity from organic acid accretion, and supports the concept that carnitine's interaction with the cellular CoA pool can have a beneficial effect on cellular metabolism and function under conditions of unusual organic acid accumulation.


2009 ◽  
Vol 34 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Gregory R. Steinberg

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.


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