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Title: Acylation and metabolism of (n-6) fatty acids in hepatocytes

Abstract

Isolated hepatocytes (5 x 10/sup 6/ in 2ml) from chow fed rats were incubated from 20 to 60 min. with increasing concentrations of (1-/sup 14/C) labeled 18:2 (n-6), 18:3 (n-6) or 20:3 (n-6) to define optimum conditions for measuring acylation and metabolism to other (n-6) acids with subsequent incorporation into lipids. The triglycerides (TG) and phospholipids (PL) contained 157 and 80 nmols of 18:2 (n-6) and 6.0 and 6.1 nmols of other (n-6) acids, respectively, when cells were incubated with 0.3mM (1-/sup 14/C) 18:2 (n-6) for 40 min. When cells were incubated with 0.3mM (1-/sup 14/C) 18:2 (n-6) plus 0.15 to 0.45mM 18:3 (n-6) or 20:3 (n-6), the metabolism of 18:2 (n-6) to other (n-6) acids was inhibited but not totally abolished. These results may suggest that (n-6) acid made from linoleate do not totally equilibrate with exogenous 18:3 (n-6) or 20:3 (n-6).

Authors:
;
Publication Date:
Research Org.:
Ohio State Univ., Columbus
OSTI Identifier:
5277863
Alternate Identifier(s):
OSTI ID: 5277863
Report Number(s):
CONF-8606151-
Journal ID: CODEN: FEPRA
Resource Type:
Conference
Resource Relation:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States); Journal Volume: 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CARBOXYLIC ACIDS; ACYLATION; METABOLISM; CARBON 14 COMPOUNDS; LIVER CELLS; PHOSPHOLIPIDS; RATS; TRACER TECHNIQUES; TRIGLYCERIDES; ANIMAL CELLS; ANIMALS; CHEMICAL REACTIONS; ESTERS; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; LIPIDS; MAMMALS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC PHOSPHORUS COMPOUNDS; RODENTS; SOMATIC CELLS; VERTEBRATES 550501* -- Metabolism-- Tracer Techniques

Citation Formats

Voss, A.C., and Sprecher, H.. Acylation and metabolism of (n-6) fatty acids in hepatocytes. United States: N. p., 1986. Web.
Voss, A.C., & Sprecher, H.. Acylation and metabolism of (n-6) fatty acids in hepatocytes. United States.
Voss, A.C., and Sprecher, H.. Thu . "Acylation and metabolism of (n-6) fatty acids in hepatocytes". United States. doi:.
@article{osti_5277863,
title = {Acylation and metabolism of (n-6) fatty acids in hepatocytes},
author = {Voss, A.C. and Sprecher, H.},
abstractNote = {Isolated hepatocytes (5 x 10/sup 6/ in 2ml) from chow fed rats were incubated from 20 to 60 min. with increasing concentrations of (1-/sup 14/C) labeled 18:2 (n-6), 18:3 (n-6) or 20:3 (n-6) to define optimum conditions for measuring acylation and metabolism to other (n-6) acids with subsequent incorporation into lipids. The triglycerides (TG) and phospholipids (PL) contained 157 and 80 nmols of 18:2 (n-6) and 6.0 and 6.1 nmols of other (n-6) acids, respectively, when cells were incubated with 0.3mM (1-/sup 14/C) 18:2 (n-6) for 40 min. When cells were incubated with 0.3mM (1-/sup 14/C) 18:2 (n-6) plus 0.15 to 0.45mM 18:3 (n-6) or 20:3 (n-6), the metabolism of 18:2 (n-6) to other (n-6) acids was inhibited but not totally abolished. These results may suggest that (n-6) acid made from linoleate do not totally equilibrate with exogenous 18:3 (n-6) or 20:3 (n-6).},
doi = {},
journal = {Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)},
number = ,
volume = 45:6,
place = {United States},
year = {Thu May 01 00:00:00 EDT 1986},
month = {Thu May 01 00:00:00 EDT 1986}
}

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  • Hepatocytes were isolated from full-term, SGA and AGA piglets at 6 or 48 hours postpartum and were incubated with 1 mM (1-{sup 14}C)-octanoate (C8), -nonanoate (C9) or-oleate (C18:1). The cells oxidized (natom 1-C/(h 10{sup 6} cells)) C9 to Co{sub 2} (12.5) and acid soluble products (28.9) faster than C8 (10.9, 20.6, respectively), and both were oxidized faster than C18:1 (3.9, 9.9) regardless of the piglet age or weight. Oleate accumulated in lipid products 8-fold faster than C8 and C9. No differences between cells from SGA and AGA piglets were detected. Recovery of 1-C in CO{sub 2} was 48% higher inmore » incubations with cells from 48 hours old than from 6 hour old piglets. This increase was attributable to a 70% higher oxygen consumption by 48 hour old cells. Theoretical oxygen consumption rates were computed from the fatty acid flux data and compared to measured oxygen consumption. hepatocytes from SGA and AGA piglets were equally capable of satisfying more that 57% of their energy needs from fatty acid oxidation. The oxygen consumption attributable to C9 metabolism was 30% higher than observed for C8 and C18:1. All fatty acids apparently spared endogenous fuels to a greater degree in 6 hour than in 48 hour piglets.« less
  • Isolated caprine hepatocytes were incubated with fatty acids of various chain lengths. Short-chain fatty acids effects on rates of gluconeogenesis and oxidation from (2-/sup 14/C) propionate were determined. Additions of glucose (2.5 mM) had no effect on hepatic (2-/sup 14/C)-propionate metabolism in the presence and absence of amino acids. A complete mixture of amino acids increased label incorporation from (2-/sup 14/C) propionate into (/sup 14/C) glucose by 22%. Butyrate inhibited (2-/sup 14/C) propionate metabolism and increased the apparent Michaelis constant for (2-/sup 14/C) propionate incorporation into (/sup 14/C) glucose from 2.4 +/- 1.5 to 5.6 +/- .9 mM. Butyrate's effectsmore » on propionate were similar in the presence and absence of L-carnitine (1 mM). Isobutyrate, 2-methylbutyrate, and valerate (1.25 mM) had no effect on (/sup 14/C) glucose production but decreased /sup 14/CO/sub 2/ production to 57, 61, and 54% of the control (2-/sup 14/C) propionate (1.25 mM). This inhibition on /sup 14/CO/sub 2/ was not competitive. Isovalerate had no effect on either (2-/sup 14/C) propionate incorporation into glucose of CO/sub 2/. An increase in ratio of (/sup 14/C) glucose to /sup 14/CO/sub 2/ from (2-/sup 14/C)-propionate demonstrated that short-chain fatty acids other than butyrate do not inhibit gluconeogenesis from propionate. In addition, fatty acids that generate a net synthesis of intracellular oxaloacetate may partition propionate carbons toward gluconeogenic rather than oxidative pathways in goat hepatocytes.« less
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  • N-nitrosodialkylamines are known to be carcinogenic in laboratory animals giving rise to hepatocellular carcinomas and a variety of other neoplasms in different organs of the body. The liver is the main target organ for tumor production in the rat; however, the biological effects of the C/sub 1/ (N-nitrosodimethylamine) through C/sub 4/ (N-nitrosodi-n-butylamine) series of symmetrical N-nitrosodialkylamines are dependent on the route of administration, the absolute dose, and the dosing regimen. For those reasons the authors have chosen to study the metabolism of N-nitrosodialkylamines in isolated rat hepatocytes. These studies were designed to compare the metabolism of the N-nitrosodialkylamines in hepatocytesmore » isolated from control and EtOH-treated rates. For instance, after incubation of /sup 14/C-diethylnitrosamine (15 ..mu..M) with hepatocytes from control animals for 3 hours, 9% of the dose was metabolized to CO/sub 2/, 2% was found associated with the acid precipitable fraction and no radioactivity was associated with the DNA. In contrast to these results, however, in similar studies using hepatocytes isolated from EtOH-treated rats, 25% of the dose was metabolized to CO/sub 2/, 2.9% was incorporated into the acid precipitable fraction and 0.8% was associated with the DNA. These data demonstrate that EtOH treatment of rats results in increased hepatocellular metabolism of diethyl nitrosamine including the generation of DNA alkylating intermediates.« less
  • The straight chain radiolabeled fatty acid (FA) show relatively rapid myocardial washout since they could be metabolized by the beta-oxidation and undergo in vivo deiodination. The high levels of free radioiodide in blood requires a special background correction. The use of p-iodo-phenylpentadecanoic acid stabilizes the iodine on the aromatic ring and lowers the amount of free iodide in the blood. This agent was evaluated in many patients, however, translocation of activity from the heart is evident, not as a result of deiodination but as p-Iodo-benzoic acid as a metabolite. To determine whether an analogue designed to inhibit the FA beta-oxidationmore » metabolic process in the myocardium could be a valuable tracer for assessing the myocardial metabolic integrity, we synthesized 1-/sup 14/C-beta-methylheptadecanoic acid (/sup 14/C-BMHDA), a FA analogue. Biodistribution of /sup 14/C-BMHDA was determined in rats (groups of six) in 5 tissues and blood at 5, 15, 30 and 60 minutes and compared to /sup 14/C-palmitic acid (/sup 14/C-PA) a normal FA. A heart concentration of 2.82 and 4.18% I.D./gr at 5 and 60 minutes was observed for /sup 14/C-BMHDA, while /sup 14/C-palmitic acid was 2.65 and 0.89% I.D./gr at 5 and 60 minutes, respectively. 1 ref., 1 tab.« less