Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart

Abstract

. Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart. Am J Physiol Heart Circ Physiol 288: H2611-H2619, 2005 C]20:4 n-6), and kinetic parameters were assessed using a steady-state radiotracer model. Heart norepinephrine and epinephrine levels were decreased 82 and 85%, respectively, in denervated rats, and this correlated with a 34% reduction in weight gain in treated rats. Fatty acid tracer uptake was not significantly different between groups for either tracer, although the dilution coefficient was increased in [1-14 C]20:4 n-6-infused rats, which indicates that less 20:4 n-6 was recycled in denervated rats. In [1-14 C]16:0-infused rats, incorporation rate and turnover values of 16:0 in stable lipid compartments were unchanged, which is indicative of preservation of ␤-oxidation. In [1-14 C]20:4 n-6-infused rats, there were dramatic reductions in incorporation rate (60 -84%) and turnover value (56 -85%) in denervated rats that were dependent upon the lipid compartment. In addition, phospholipase A2 activity was reduced 40% in treated rats, which is consistent with the reduction observed in 20:4 n-6 turnover. These results demonstrate marked reductions in 20:4 n-6 incorporation rate and turnover in sympathetic denervated rats and thereby suggest an effect on lipid-mediated signal transduction mediated by a reduction in phospholipase A2 activity. palmitic acid; signal transduction; phospholipase A 2; catecholamines; phospholipids UNDER NORMAL PHYSIOLOGICAL conditions, the mammalian heart uses palmitic acid (16:0) as a primary source of metabolic energy via ␤-oxidation (11

RETRACTED ARTICLE: Chronic fluoxetine increases cytosolic phospholipase A2 activity and arachidonic acid turnover in brain phospholipids of the unanesthetized rat

“…The model for determining in vivo kinetics of brain fatty acids in rats has been described in detail elsewhere Robinson et al 1992) and has also been used to determine in vivo fatty acid kinetics in the heart (Patrick et al 2005). Briefly, unidirectional incorporation coefficients, k à i ml Á s À1 Á g À1 ð Þof AA, representing incorporation from plasma into brain phospholipid compartments i, were calculated as:…”

Mouse Strain Impacts Fatty Acid Uptake and Trafficking in Liver, Heart, and Brain: A Comparison of C57BL/6 and Swiss Webster Mice

“…While the reduction in targeting of [1-14 C]16:0 and [1-14 C]22:6n-3 to EtnGpl and ChoGpl may be a result of reduced sPLA 2 activity, the lack of a reduction in 20:4n-6 incorporation into these mice suggest the decreased activity of sPLA 2 may not be critical for the changes observed between strains. However, in denervated rat heart, a reduction in general PLA 2 activity results in decreased 20:4n-6 turnover, which causes a reduction of 20:4n-6 incorporation into stable lipid compartments [42]. This is in contrast to our data as we observed a broad increase in esterification of 20:4n-6 into heart phospholipids in C57BL/6 mice, suggesting the difference in uptake and incorporation are not a result of this mutation in sPLA 2 .…”

“…TAG [18]. In rodents, 16:0 incorporation and turnover in TAG is very rapid indicating its use in β-oxidation [42]. Further, in rat lipid metabolism, 16:0, a saturated fatty acid, is mainly targeted towards β-oxidation [19,43], whereas 20:4n-6 is mainly esterified into phospholipids [19], suggesting substantially different roles in the heart.…”

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

“…This method has been used to determine fatty acid turnover rates for the brain, 70 liver 32 and heart. 71 Quantitative autoradiography also allows one to determine incorporation coefficients for unesterified fatty acids from plasma into brain phospholipids within specific brain regions. With the synthesis of positron emitting 11 C fatty acids, similar to quantitative autoradiography, it is possible to measure the net uptake of unesterified fatty acids from plasma into brain regions in non-human primates 72 and in humans, 73,74 using positron emission tomography (PET).…”