Free fatty acid turnover and oxygen consumption. Effects of noradrenaline in nonfasted and nonanesthetized cold-adapted rats

1980 ◽  
Vol 58 (7) ◽  
pp. 797-804 ◽  
Author(s):  
Louise Lafrance ◽  
Georges Lagacé ◽  
Danièle Routhier

The effects of a 3-h noradrenaline (NA) infusion (1.5 μg kg−1 min−1) on the O2 consumption, the respiratory quotient (RQ), the concentration of plasma free fatty acids (FFA), and the rates of appearance (Ra) and disappearance (Rd) of plasma FFA were studied in nonfasted and nonanesthetized control and cold-adapted rats. To calculate the Ra FFA and Rd FFA, [1-14C]palmitate complexed to albumin was infused as a tracer. The concentrations of glucose and lactate in blood were also determined before and during the NA infusion. The enhanced O2 consumption produced by NA in cold-adapted rats was associated with a decreased RQ. The Ra FFA and Rd FFA were more enhanced by NA in cold-adapted than in control rats whereas the plasma FFA concentration was less elevated in cold-adapted rats. The blood lactate was barely increased by the NA infusion in cold-adapted rats and was not modified in control rats. Blood glucose was increased by NA in both control and cold-adapted rats but to a greater extent in control rats during the last 90 min of NA infusion. These results suggest that the enhanced calorigenic response to NA observed in nonfasted and nonanesthetized cold-adapted rats is related, at least partly, to an enhanced lipid metabolism; the RQ is low and Ra FFA and Rd FFA are greatly increased. However, the contribution of other energetic substrates like glucose will also be investigated in further studies.

1979 ◽  
Vol 57 (7) ◽  
pp. 725-730 ◽  
Author(s):  
Louise Lafrance ◽  
Danièle Routhier ◽  
Bernard Têtu ◽  
Christian Têtu

A 3-h noradrenaline (NA) infusion (1.5 μg kg−1 min−1) produced a sustained enhanced oxygen consumption (O2 cons.) in cold-adapted rats. Plama free fatty acid (FFA) levels were elevated by NA in control and in cold-adapted rats, but to a lesser extent in cold-adapted rats; the increase was maintained at a plateau in both groups during the entire period of NA infusion. A 1-h nicotinic acid (Nic A) infusion (1.5 mg kg−1 min−1) added to the NA infusion inhibited the calorigenic response to NA in cold-adapted rats and reduced the elevated plasma FFA concentration in control and in cold-adapted rats to values below basal levels. However, when the Nic A infusion was stopped, the O2 cons, was increased again in cold-adapted rats by the uninterrupted NA infusion, without the simultaneous increase of the plasma FFA concentration; the plasma FFA concentration was maintained in cold-adapted rats below basal values and merely brought back to basal levels in control rats. From these results, it is suggested that plasma FFA are not an essential substrate to the calorigenic response to NA observed in cold-adapted rats, as 85% of the response can occur when the plasma FFA concentration is very low.


1961 ◽  
Vol 201 (5) ◽  
pp. 815-818 ◽  
Author(s):  
John J. Spitzer ◽  
William T. McElroy

The effects of epinephrine or norepinephrine were studied in dogs receiving insulin plus glucose prior to and during administration of the amine. Epinephrine caused a significantly smaller elevation of free fatty acids (FFA) with than without insulin plus glucose administration. Blood sugar responses were quantitatively similar. Epinephrine increased both hepatic uptake of FFA and hepatic release of glucose; these changes were similar to the ones found previously in dogs not receiving insulin plus glucose. The action of norepinephrine on elevating plasma FFA was only slightly and not significantly affected by the administration of insulin plus glucose. When the order of drug administration was reversed, infusion of insulin plus glucose lowered plasma FFA levels and hepatic FFA uptake in animals already receiving either epinephrine or nonepinephrine.


1964 ◽  
Vol 19 (3) ◽  
pp. 489-492 ◽  
Author(s):  
K. Rodahl ◽  
H. I. Miller ◽  
B. Issekutz

The effects of exercise of different intensity and duration on plasma free fatty acids (FFA), blood glucose, and lactate were investigated in eight healthy young men. In heavy 10-min work the blood lactate rose rapidly and the FFA decreased. Blood sugar showed no marked change. Intermittent work caused a slight increase in blood lactate and no change in blood glucose. The FFA remained essentially unchanged but increased in three out of four subjects during recovery. In moderate 1-hr work the FFA remained essentially unchanged, but increased markedly during recovery when blood lactate had returned to resting levels. In prolonged exhausting work in fasting subjects, the blood lactate remained almost unchanged, while the FFA rose steadily and the blood sugar dropped. In nonfasting subjects the FFA also rose, but the ingestion of lunch caused, in all cases, a striking drop in the FFA, associated with a rise in blood sugar. Combined hormonal effects (insulin and norepinephrine) brought into play during exercise of different intensity and duration may well explain the apparent discrepancy in the results of different investigators concerning the effect of exercise on plasma FFA. work and FFA; FFA at different workloads; lipid metabolism in work Submitted on November 6, 1963


1977 ◽  
Vol 232 (5) ◽  
pp. E451
Author(s):  
E Hohtola ◽  
R Hissa ◽  
S Saarela

The effects of glucagon injection on temperature regulation and some metabolic parameters were studied in the pigeon. Glucagon (100 microng/kg) always inhibited shivering and caused a fall in the oxygen consumption and body temperature of the unanesthetized pigeon at + 6 degrees C. At + 34 degrees C, the same dose of glucagon had no effect on these parameters. At 22 degrees C, glucagon produced an elevation in plasma free fatty acid (FFA) and blood glucose levels. The rise in FFA at 22 degrees C coincided with the suppression of shivering at 6 degrees C. The glucagon-mediated rise in plasma FFA, but not glucose level, was potentiated by cold ambient temperature. Adrenergic blocking agents given prior to glucagon did not abolish its effects. Phentolamine even prolonged the absence and accelerated the suppression of shivering. A dissociation in the mechanisms by which catecholamines and glucagon suppress shivering is suggested. Although mobilizing energy reserves, glucagon does not seem to be calorigenic in the pigeon at this dose. The interpretation of the changes in plasma FFA levels is discussed in relation to fuel consumption during shivering.


1984 ◽  
Vol 102 (3) ◽  
pp. 381-386 ◽  
Author(s):  
R. Gross ◽  
P. Mialhe

ABSTRACT To elucidate the hypolipacidaemic effect of insulin in ducks, its action on the uptake of free fatty acids (FFA) by duck hepatocytes was determined. At low doses (10 mu./l) insulin stimulated FFA uptake. This effect was not observed with higher doses of insulin (20, 30 and 50 mu./l). Growth hormone at physiological concentrations and corticosterone (14·4 nmol/l) decreased basal activity, probably by reducing glucose metabolism and consequently α-glycerophosphate (α-GP) supply. Insulin was able to reverse the inhibition induced by GH and corticosterone on both FFA uptake and α-GP production. These results therefore suggest that the hypolipacidaemic effect of insulin may be partly mediated by its action on hepatic FFA uptake. J. Endocr. (1984) 102, 381–386


2019 ◽  
Author(s):  
Mohammad Aziz ◽  
Saeed Al Mahri ◽  
Amal Alghamdi ◽  
Maaged AlAkiel ◽  
Monira Al Aujan ◽  
...  

Abstract Background Colorectal cancer is a worldwide problem which has been associated with changes in diet and lifestyle pattern. As a result of colonic fermentation of dietary fibres, short chain free fatty acids are generated which activate Free Fatty Acid Receptors 2 and 3 (FFAR2 and FFAR3). FFAR2 and FFAR3 genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells. Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis. Methods Transcriptome analysis console was used to analyse microarray data from patients and cell lines. We employed shRNA mediated down regulation of FFAR2 and FFAR3 genes which was assessed using qRT-PCR. Assays for glucose uptake and cAMP generation was done along with immunofluorescence studies. For measuring cell proliferation, we employed real time electrical impedance based assay available from xCelligence. Results Microarray data analysis of colorectal cancer patient samples showed a significant down regulation of FFAR2 gene expression. This prompted us to study the FFAR2 in colorectal cancer. Since, FFAR3 shares significant structural and functional homology with FFAR2, we knocked down both these receptors in colorectal cancer cell line HCT 116. These modified cell lines exhibited higher proliferation rate and were found to have increased glucose uptake as well as increased level of GLUT1. Since, FFAR2 and FFAR3 signal through G protein subunit (Gαi), knockdown of these receptors was associated with increased cAMP. Inhibition of PKA did not alter the growth and proliferation of these cells indicating a mechanism independent of cAMP/PKA pathway. Conclusion: Our results suggest role of FFAR2/FFAR3 genes in increased proliferation of colon cancer cells via enhanced glucose uptake and exclude the role of protein kinase A mediated cAMP signalling. Alternate pathways could be involved that would ultimately result in increased cell proliferation as a result of down regulated FFAR2/FFAR3 genes. This study paves the way to understand the mechanism of action of short chain free fatty acid receptors in colorectal cancer.


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.


2002 ◽  
Vol 282 (2) ◽  
pp. E402-E411 ◽  
Author(s):  
Chang An Chu ◽  
Stephanie M. Sherck ◽  
Kayano Igawa ◽  
Dana K. Sindelar ◽  
Doss W. Neal ◽  
...  

The aim of this study was to determine the effect of high levels of free fatty acids (FFA) and/or hyperglycemia on hepatic glycogenolysis and gluconeogenesis. Intralipid was infused peripherally in 18-h-fasted conscious dogs maintained on a pancreatic clamp in the presence (FFA + HG) or absence (FFA + EuG) of hyperglycemia. In the control studies, Intralipid was not infused, and euglycemia (EuG) or hyperglycemia (HG) was maintained. Insulin and glucagon were clamped at basal levels in all four groups. The arterial blood glucose level increased by 50% in the HG and FFA + HG groups. It did not change in the EuG and FFA + EuG groups. Arterial plasma FFA increased by ∼140% in the FFA + EuG and FFA + HG groups but did not change significantly either in the EuG or HG groups. Arterial glycerol levels increased by ∼150% in both groups. Overall (3-h) net hepatic glycogenolysis was 196 ± 26 mg/kg in the EuG group. It decreased by 96 ± 20, 82 ± 16, and 177 ± 22 mg/kg in the HG, FFA + EuG, and FFA + HG groups, respectively. Overall (3-h) hepatic gluconeogenic flux was 128 ± 22 mg/kg in the EuG group, but it was suppressed by 30 ± 9 mg/kg in response to hyperglycemia. It was increased by 59 ± 12 and 56 ± 10 mg/kg in the FFA + EuG and FFA + HG groups, respectively. In conclusion, an increase in plasma FFA and glycerol significantly inhibited hepatic glycogenolysis and markedly stimulated hepatic gluconeogenesis.


1961 ◽  
Vol 200 (5) ◽  
pp. 1095-1098 ◽  
Author(s):  
Frank J. Hohenleitner ◽  
John J. Spitzer

To measure the renal removal of free fatty acids from the plasma, simultaneous determinations of this metabolite were performed in a systemic artery and a renal vein in the anesthetized dogs. Renal plasma flow was also determined by the PAH method, and the renal uptake of free fatty acids was calculated. Concentrations of free fatty acids in renal venous plasma were usually lower than the arterial concentrations. The arteriovenous differences were statistically highly significant. The results also suggested that the degree of free fatty acid removal was proportional to the arterial concentration of this metabolite.


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