scholarly journals Circulating free fatty acids are increased independently of PPARγ activity after administration of poloxamer 407 to mice

2008 ◽  
Vol 86 (9) ◽  
pp. 643-649 ◽  
Author(s):  
Thomas P. Johnston ◽  
David J. Waxman

Poloxamer 407 (P-407) is a copolymer surfactant that induces a dose-controlled dyslipidemia in both mice and rats. Human macrophages cultured with P-407 exhibit a concentration-dependent reduction in cholesterol efflux to apolipoprotein A1 (apoA1) linked to downregulation of the ATP-binding cassette transporter A1 (ABCA1). Activators of peroxisome proliferator-activated receptor gamma (PPARγ), as well as PPARα, increase expression of liver X receptor alpha (LXRα) in macrophages and promote the expression of ABCA1, which, in turn, mediates cholesterol efflux to apoA1. The present study investigated whether P-407 interferes with this signaling pathway. A transactivation assay was used to evaluate whether P-407 can either activate or inhibit the transcriptional activity of PPARγ. Because thiazolidinedione drugs (PPARγ agonists) improve glycemic control in type 2 diabetes by reducing blood glucose concentrations, P-407 was also evaluated for its potential to alter plasma insulin and blood glucose concentrations in wild-type (C57BL/6) and PPARγ-deficient mice. Additionally, because thiazolidinediones attenuate release of free fatty acids (FFAs) from adipocytes and, consequently, decrease circulating plasma levels of FFAs, plasma concentrations of circulating FFAs were also determined in P-407-treated mice. P-407 was unable to modulate PPARγ activity in cell-based transactivation assays. Furthermore, P-407 did not perturb plasma insulin and blood glucose concentrations after administration to mice. However, by an as yet unidentified mechanism, P-407 caused a significant increase in the serum concentration of FFAs in mice beginning 3 h after administration and lasting more than 24 h postdosing. It is concluded that P-407 does not interfere with the functional activity of PPARγ after administration to mice.

1971 ◽  
Vol 125 (2) ◽  
pp. 541-544 ◽  
Author(s):  
R. A. Hawkins ◽  
K. G. M. M. Alberti ◽  
C. R. S. Houghton ◽  
D. H. Williamson ◽  
H. A. Krebs

1. Sodium acetoacetate was infused into the inferior vena cava of fed rats, 48h-starved rats, and fed streptozotocin-diabetic rats treated with insulin. Arterial blood was obtained from a femoral artery catheter. 2. Acetoacetate infusion caused a fall in blood glucose concentration in fed rats from 6.16 to 5.11mm in 1h, whereas no change occurred in starved or fed–diabetic rats. 3. Plasma free fatty acids decreased within 10min, from 0.82 to 0.64mequiv./l in fed rats, 1.16 to 0.79mequiv./l in starved rats and 0.83 to 0.65mequiv./l in fed–diabetic rats. 4. At 10min the plasma concentration rose from 20 to 49.9μunits/ml in fed unanaesthetized rats and from 6.4 to 18.5μunits/ml in starved rats. There was no change in insulin concentration in the diabetic rats. 5. Nembutal-anaesthetized fed rats had a more marked increase in plasma insulin concentration, from 30 to 101μunits/ml within 10min. 6. A fall in blood glucose concentration in fed rats and a decrease in free fatty acids in both fed and starved rats is to be expected as a consequence of the increase in plasma insulin. 7. The fall in the concentration of free fatty acids in diabetic rats may be due to a direct effect of ketone bodies on adipose tissue. A similar effect on free fatty acids could also be operative in normal fed or starved rats.


1968 ◽  
Vol 58 (4) ◽  
pp. 545-557 ◽  
Author(s):  
M. Karp ◽  
A. Pertzelan ◽  
M. Doron ◽  
A. Kowadlo-Silbergeld ◽  
Z. Laron

ABSTRACT Lysine-8-vasopressin (LVP) was administered intramuscularly in a dose of 5–10 units to 20 children and adolescents, divided into the following 3 groups: I – normal controls; II – patients with isolated growth hormone deficiency; III – patients with pituitary insufficiency involving several hormones. In all the patients studied, LVP induced a rise in plasma 11-hydroxycorticosteroids. In the normal controls LVP induced a moderate rise in blood glucose. Patients with isolated growth hormone deficiency showed no rise, and those with pituitary insufficiency involving several hormones showed a great variability in response. In all 3 groups there was a sharp decrease in plasma free fatty acids, most marked in the patients with isolated growth hormone deficiency, and a slower return to base line levels. There was no change in the plasma concentration of growth hormone in any of the patients. Plasma insulin rose moderately in the normal controls; there was little or no change in any of the patients with pituitary insufficiency. The above finding that LVP induced a reduction in plasma free fatty acids in the patients with pituitary insufficiency without any concomitant elevation of plasma insulin and blood glucose, is in agreement with the assumption that LVP acts directly on adipose tissue.


1998 ◽  
Vol 8 (1) ◽  
pp. 24-35 ◽  
Author(s):  
Kieran E. Fallon ◽  
Elizabeth Broad ◽  
Martin W. Thompson ◽  
Patricia A. Reull

The fluid and food intakes of 7 male participants in a 100-km ultramarathon were recorded. The mean exercise time was 10 hr 29 min. Nutrient analysis revealed a mean inlrarace energy intake of 4.233 kJ. with 88.6% derived from carbohydrate. 6.7% from fat, and 4.7% from protein. Fluid intake varied widely. 3.3–1 1.1 L, with a mean of 5.7 L. The mean decrease in plasma volume at 100 km was 7.3%, accompanied by an estimated mean sweat rale of 0.86 L ⋅ hr−1. Blood glucose concentrations remained normal during the event, and free fatty acids and glycerol were elevated both during and at the conclusion of the event. No significant correlations were found between absolute amounts and rates of ingestion of carbohydrate and/or fluid and race performance.


1984 ◽  
Vol 247 (6) ◽  
pp. E765-E771 ◽  
Author(s):  
A. B. Steffens ◽  
G. Damsma ◽  
J. van der Gugten ◽  
P. G. Luiten

The aim of this study was to investigate plasma free fatty acids (FFA), insulin, and blood glucose during chemical stimulation of the lateral and ventromedial hypothalamic areas (LHA and VMH) in rats. Therefore male Wistar rats were implanted with bilateral cannulas in the LHA or the VMH and into the left and right jugular veins. Freely moving rats were then infused into the LHA and VMH with norepinephrine (NE), epinephrine (E), or acetylcholine or intravenously with NE or E. Before, during, and after the infusions, simultaneous blood samples were taken without disturbing the animals. Infusion of NE into the LHA resulted in a decrease of plasma FFA and a simultaneous increase of insulin. NE infusion in the VMH elicited an increase of plasma FFA, plasma insulin, and blood glucose. E infusion into the LHA did not lead to a change of plasma FFA, whereas insulin and glucose showed an increase. E infusion into the VMH evoked increases of plasma FFA and insulin. Peripheral administration of NE led to a sharp increase of FFA, whereas plasma insulin and blood glucose did not change. E in the periphery elicited an augmentation of plasma FFA and blood glucose and a suppression of insulin during infusion. After termination of E infusion, plasma FFA and glucose levels decreased, whereas plasma insulin showed a sharp increase.(ABSTRACT TRUNCATED AT 250 WORDS)


1997 ◽  
Vol 78 (5) ◽  
pp. 805-813 ◽  
Author(s):  
Kjell Holtenius ◽  
Paul Holtenius

The metabolic effects of a phlorizin-induced drainage of glucose were studied in six lactating ewes with or without peroral alanine drenches in a study of crossover design. Phlorizin gave rise to a small, but significant, elevation of plasma β-hydroxybutyrate. The plasma level of alanine decreased by about 30 % due to the phlorizin injections and alanine was negatively correlated to β-hydroxybutyrate. The plasma level of free fatty acids increased due to phlorizin. Plasma insulin and glucose concentrations were not significantly affected by phlorizin while glucagon level showed a small but significant increase. Peroral alanine drenches to phlorizin-treated ewes gave rise to a transitory elevation of alanine in plasma. The plasma level of free fatty acids was about 40 % lower in phlorizin-treated ewes receiving alanine and β-hydroxybutyrate tended to be lower (P < 0.08). We suggest that β-hydroxybutyrate, apart from its function as an oxidative fuel, might play an important role by limiting glucose oxidation and protein degradation in skeletal muscles during periods of negative energy balance in ruminants. Furthermore, it is suggested that alanine supplementation decreases lipolysis and ketogenesis in lactating ewes.


2009 ◽  
Vol 205 (1-6) ◽  
pp. 299-301 ◽  
Author(s):  
Harald Wang ◽  
Knut Rasmussen ◽  
Harald Vik-Mo ◽  
Ole D. Mjøs ◽  
Helge Grendahl

1986 ◽  
Vol 106 (2) ◽  
pp. 209-217 ◽  
Author(s):  
Sarah C. Bolton ◽  
T. E. C. Weekes

SUMMARYAdrenaline was infused at three rates, 40, 15 or 3 μ/kg/h, in normal sheep and in sheep rendered hypercortisolaemic by infusion of cortisol at 150 μg/kg/h. In both normal and hypercortisolaemic animals, plasma concentrations of glucose and free fatty acids were increased by adrenaline treatment; plasma phosphate decreased with all treatments; plasma magnesium and potassium decreased on infusion of adrenaline at 40 or 15, but not at 3 μg/kg/h; plasma calcium decreased only on infusion of adrenaline in hypercortisolaemic animals, and plasma sodium concentration was unaffected by treatment.Induction of a degree of lipolysis likely to occur in the field was not associated with a marked decrease in plasma magnesium.


1991 ◽  
Vol 71 (5) ◽  
pp. 1807-1812 ◽  
Author(s):  
I. Tabata ◽  
F. Ogita ◽  
M. Miyachi ◽  
H. Shibayama

The effects of low blood glucose concentration during low-intensity prolonged physical exercise on the hypothalamus-pituitary-adrenocortical axis were investigated in healthy young men. In experiment 1, six subjects who had fasted for 14 h performed bicycle exercise at 50% of their maximal O2 uptake until exhaustion. At the end of the exercise, adrenocorticotropic hormone (ACTH) and cortisol increased significantly. However, this hormonal response was totally abolished when the same subjects exercised at the same intensity while blood glucose concentrations were maintained at the preexercise level. In experiment 2, in addition to ACTH and cortisol, the possible changes in plasma concentration of corticotropin-releasing factor (CRF) were investigated during exercise of the same intensity performed by six subjects. As suggested by a previous study (Tabata et al. Clin. Physiol. Oxf. 4: 299–307, 1984), when the blood glucose concentrations decreased to less than 3.3 mM, plasma concentrations of CRF, ACTH, and cortisol showed a significant increase. At exhaustion, further increases were observed in plasma CRF, ACTH, and cortisol concentrations. These results demonstrate that decreases in blood glucose concentration trigger the pituitary-adrenocortical axis to enhance secretion of ACTH and cortisol during low-intensity prolonged exercise in humans. The data also might suggest that this activation is due to increased concentration of CRF, which was shown to increase when blood glucose concentration decreased to a critical level of 3.3 mM.


1988 ◽  
Vol 255 (4) ◽  
pp. R547-R556 ◽  
Author(s):  
A. J. Scheurink ◽  
A. B. Steffens ◽  
L. Benthem

The effects of intravenously and intrahypothalamically administered alpha- and beta-adrenoceptor antagonists on exercise-induced alterations in blood glucose, plasma free fatty acids (FFA), and insulin were investigated in rats. Exercise consisted of strenuous swimming against a counter current for 15 min. Before, during, and after swimming, blood samples were withdrawn through a permanent heart catheter. Intravenous administration of the alpha-blocker phentolamine led to a reduction in glucose and a substantial increase in insulin levels. Infusion of phentolamine through permanent bilateral cannulas into either the ventromedial or lateral area of the hypothalamus (VMH and LHA, respectively) completely prevented the increase in glucose while the decline in insulin was unaffected. Infusion of phentolamine into the VMH caused much higher plasma FFA levels than in controls. The beta-blocker timolol given intravenously caused a delayed increase in glucose and prevented the increase in FFA. Infusion of timolol into either VMH or LHA caused a delay in the increase in both glucose and FFA. The results suggest that 1) both peripheral and hypothalamic adrenoceptors are involved in energy metabolism during exercise and 2) FFA, glucose, and insulin concentrations in blood are independently regulated by VMH and LHA.


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