Fish Oil/ relationship btwn EPA and GLA - For research geeks only ;-)

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Chapkin RS Somers SD kson KL

Dietary manipulation of macrophage phospholipid classes: selective

increase of dihomogammalinolenic acid.

In: Lipids (1988 Aug) 23(8):766-70

Because alterations in the dietary content of fatty acids are an

important method for modulating macrophage eicosanoid production, we

have quantitated the levels of n-6 and n-3 polyunsaturated fatty

acids in peritoneal macrophage individual phospholipids from mice

fed diets (3 wk) with either safflower oil (SAF), predominantly

containing 18:2n-6, borage, (BOR) containing 18:2n-6 and 18:3n-6,

fish (MFO) containing 20:5n-3 and 22:6n-3, and borage/fish mixture

(MIX) containing 18:2n-6, 18:3n-6, 20:5n-3 and 22:6n-3. Dietary n-3

fatty acids were readily incorporated into macrophage

phosphatidylcholine (PC), phosphatidylethanolamine (PE),

phosphatidylserine (PS) and phosphatidylinositol (PI). The increase

in n-3 fatty acid levels was accompanied by a decrease in the

absolute levels of 18:2n-6, 20:4n-6 and 22:4n-6 in PC, PE and PS.

Interestingly, PI 20:4n-6 levels were not significantly lowered (P

greater than 0.05) in MIX and MFO macrophages relative to SAF and

BOR. These data demonstrate the unique ability of this phospholipid

to selectively maintain its 20:4n-6 levels. In BOR and MIX animals,

20:3n-6 levels were significantly increased (P less than 0.05) in

all phospholipids relative to SAF and MFO. The combination of borage

and fish oils (MIX diet) produced the highest 20:3n-6/20:4n-6 ratio

in all phospholipids. These data show that the macrophage eicosanoid

precursor levels of 20:3n-6, 20:4n-6 and n-3 acids can be

selectively manipulated through the use of specific dietary

regimens. This is noteworthy because an increase in phospholipid

levels of 20:3n-6 and 20:5n-3, while concomitantly reducing 20:4n-6,

may have therapeutic potential in treating inflammatory disorders.

Institutional address: Department of Human Anatomy School of

Medicine University of California 95616.

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Chapkin RS Carmichael SL

Effects of dietary n-3 and n-6 polyunsaturated fatty acids on

macrophage phospholipid classes and subclasses.

In: Lipids (1990 Dec) 25(12):827-34

This study examined the effects of n-3 and n-6 polyunsaturated fatty

acid alimentation on murine peritoneal macrophage phospholipids.

Mice were fed complete diets supplemented with either corn oil

predominantly containing 18:2n-6, borage oil containing 18:2n-6 and

18:3n-6, fish/corn oil mixture containing 18:2n-6, 20:5n-3 and 22:6n-

3, or fish/borage oil mixture containing 18:2n-6, 18:3n-6, 20:5n-3

and 22:6n-3. After two weeks, the fatty acid levels of

glycerophosphoserines (GPS), glycerophosphoinositols (GPI),

sphingomyelin (SPH), and of the glycerophosphocholine (GPC) and

glycerophosphoethanolamine (GPE) phospholipid subclasses were

determined. We found that mouse peritoneal macrophage GPC contain

primarily 1-O-alkyl-2-acyl (range for the dietary groups, 24.6-30.5

mol %) and 1,2-diacyl (63.2-67.2 mol %), and that GPE contains 1-O-

alk-1'-enyl-2-acyl (40.9-47.4 mol %) and 1,2-diacyl (44.2-51.2 mol

%) subclasses. In general, fish oil feeding increased macrophage

20:5n-3, 22:5n-3 and 22:6n-3 levels while simultaneously reducing

20:4n-6 in GPS, GPI, GPE and GPC subclasses except for 1-O-alk-1'-

enyl-2-acyl GPC. Administration of 18:3n-6 rich diets (borage and

fish/borage mixture) resulted in the accumulation of 20:3n-6 (2-

carbon elongation product of 18:3n-6) in most phospholipids. In

general, the novel combination of dietary 18:3n-6 and n-3 PUFA

produced the highest 20:3n-6/20:4n-6 phospholipid fatty acid ratios.

This study demonstrates that marked differences in the responses of

macrophage phospholipid classes and subclasses exist following

dietary manipulation.

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Fan YY Chapkin RS

Mouse peritoneal macrophage prostaglandin E1 synthesis is altered by

dietary gamma-linolenic acid.

In: J Nutr (1992 Aug) 122(8):1600-6

The ability of dietary gamma-linolenic acid [18:3(n-6)] to modulate

prostaglandin biosynthesis in mouse resident peritoneal macrophages

was determined. Mice were fed diets containing corn oil, borage oil

or evening primrose oil or a mixture of borage and fish oils. After

2 wk, resident peritoneal macrophages were isolated and stimulated

with unopsonized zymosan to induce prostaglandin synthesis. Borage

oil, primrose oil and fish-borage oil mixture dietary groups

(containing 25.6, 11.9 and 19.5 g gamma-linolenic acid/100 g fatty

acids, respectively) had significantly (P less than 0.05) enhanced

prostaglandin E1 synthesis (39.7, 29.4 and 73.0 nmol prostaglandin

E1/mg protein, respectively) compared with corn oil-fed (containing

less than 0.1 g gamma-linolenic acid/100 g fatty acids) animals,

which synthesized less than 0.1 nmol prostaglandin E1/mg protein.

Borage oil- and fish-borage oil mixture-fed mice had the highest

biosynthetic ratio of prostaglandin E1/prostaglandin E2 (E1/E2

approximately 0.2). Macrophages from borage oil-fed mice synthesized

the lowest amount of prostacyclin (198.7 nmol 6-keto-prostaglandin

F1 alpha/mg protein) compared with corn oil-, primrose oil- and fish-

borage oil mixture-fed mice (379.7, 764.8 and 384.2 nmol 6-keto-

prostaglandin F1 alpha/mg protein, respectively). In addition,

borage oil-, primrose oil- and fish-borage oil mixture-fed mice had

significantly (P less than 0.05) higher levels of dihomo-gamma-

linolenic acid [20:3(n-6)] in membrane phospholipids (5.5, 3.5 and

5.7 mol/100 mol, respectively) relative to corn oil-fed mice (2.0

mol/100 mol).

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Fan YY Chapkin RS Ramos KS

Dietary lipid source alters murine macrophage/vascular smooth muscle

cell interactions in vitro.

In: J Nutr (1996 Sep) 126(9):2083-8

This study was conducted to compare the impact of dietary lipids on

the ability of macrophages to modulate vascular smooth muscle cell

(SMC) DNA synthesis in vitro. C57BL/6 female mice were fed six

different diets (6 mice/diet) containing 10% fat from corn oil (CO),

borage oil (BO), primrose oil (PO), fish-corn oil mix (FC, 9:1,

w/w), fish-borage oil mix (FB, 1:3, w/w), or fish-primrose oil mix

(FP, 1:3, w/w) for 2 wk. Peritoneal macrophages were isolated from

these mice, stimulated with zymosan or vehicle, and subsequently co-

cultured with naive mouse aortic SMC in the presence of 3H-thymidine

to measure SMC DNA synthesis. In this co-culture system, macrophages

were seeded on 25-mm culture inserts (upper chamber) and SMC were

seeded on 35-mm culture dishes (lower chamber). The two cell types

were separated by a semipermeable membrane with a 30-kD cut-off.

When quiescent SMC were co-cultured with macrophages, only the PO

and FP diet groups had significantly (P < 0.05) lower SMC DNA

synthesis compared with the control CO group whose diet contained no

gamma- linolenic acid (GLA) or (n-3) polyunsaturated fatty acids

(PUFA). In contrast, when cycling SMC were co-cultured with diet-

modulated macrophages, all dietary groups except for those fed FC

had significantly lower (P < 0.05) SMC DNA synthesis relative to the

CO group. Although the level of GLA in PO and BO diets was different

(11.5 and 22.3 g/100 g fatty acids, respectively), these treatments

exerted comparable inhibitory effects on SMC DNA synthesis. The FP

treatment consistently exhibited the lowest SMC DNA synthetic

profile among the six dietary groups irrespective of SMC growth

conditions. These data suggest that BO and PO alone or in

combination with fish oil influence macrophage/smooth muscle cell

interactions in a manner consistent with favorable modulation of the

atherogenic process.