Plasma prostaglandin levels in fed and starved lean, normal and obese women

Curtis-Prior, P.B.; Jenner, M.; Smethurst, Michael; Woodward, J. W.

doi:10.1007/bf01955144

Cited by 8 publications

(3 citation statements)

References 10 publications

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“…Reports on a positive correlation between plasma prostaglandin concentration and adiposity or insulin resistance are inconsistent 9, 26. Due to the efficient elimination in liver and lung, plasma prostanoid concentrations are below the concentration of PGE 2 that caused insulin resistance in the current study (10 μM) and the lowest PGE 2 concentration at which the attenuation of insulin signaling was observed (100 nM, not shown).…”

Section: Discussioncontrasting

confidence: 63%

Aggravation by prostaglandin E2 of interleukin-6-dependent insulin resistance in hepatocytes

Henkel

Neuschäfer-Rube

Pathe-Neuschäfer-Rube

et al. 2009

Hepatology

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Hepatic insulin resistance is a major contributor to fasting hyperglycemia in patients with metabolic syndrome and type 2 diabetes. Circumstantial evidence suggests that cyclooxygenase products in addition to cytokines might contribute to insulin resistance. However, direct evidence for a role of prostaglandins in the development of hepatic insulin resistance is lacking. Therefore, the impact of prostaglandin E 2 (PGE 2 ) alone and in combination with interleukin-6 (IL-6) on insulin signaling was studied in primary hepatocyte cultures. Rat hepatocytes were incubated with IL-6 and/or PGE 2 and subsequently with insulin. Glycogen synthesis was monitored by radiochemical analysis; the activation state of proteins of the insulin receptor signal chain was analyzed by western blot with phosphospecific antibodies. In hepatocytes, insulin-stimulated glycogen synthesis and insulin-dependent phosphorylation of Akt-kinase were attenuated synergistically by prior incubation with IL-6 and/or PGE 2 while insulin receptor autophosphorylation was barely affected. IL-6 but not PGE 2 induced suppressors of cytokine signaling (SOCS3). PGE 2 but not IL-6 activated extracellular signal-regulated kinase 1/2 (ERK1/2) persistently. Inhibition of ERK1/2 activation by PD98059 abolished the PGE 2 -dependent but not the IL-6-dependent attenuation of insulin signaling. In HepG2 cells expressing a recombinant EP3-receptor, PGE 2 pre-incubation activated ERK1/2, caused a serine phosphorylation of insulin receptor substrate 1 (IRS1), and reduced the insulin-dependent Akt-phosphorylation. Conclusion: PGE 2 might contribute to hepatic insulin resistance via an EP3-receptor-dependent ERK1/2 activation resulting in a serine phosphorylation of insulin receptor substrate, thereby preventing an insulindependent activation of Akt and glycogen synthesis. Since different molecular mechanisms appear to be employed, PGE 2 may synergize with IL-6, which interrupted the insulin receptor signal chain, principally by an induction of SOCS, namely SOCS3. (HEPATOLOGY 2009;50: 781-790.)

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Section: Discussioncontrasting

confidence: 63%

Aggravation by prostaglandin E2 of interleukin-6-dependent insulin resistance in hepatocytes

Henkel

Neuschäfer-Rube

Pathe-Neuschäfer-Rube

et al. 2009

Hepatology

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“…This condition has been proposed as a potential mechanism linking obesity with metabolic diseases [4]–[6]. Among the many inflammatory factors secreted by adipose tissue, prostaglandins (PGs) have been proposed as contributing mediators of inflammation in obesity, hyperinsulinemia, hypertension and cardiovascular disease [7]–[9].…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin (PG) F2 Alpha Synthesis in Human Subcutaneous and Omental Adipose Tissue: Modulation by Inflammatory Cytokines and Role of the Human Aldose Reductase AKR1B1

et al. 2014

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IntroductionPGF2α may be involved in the regulation of adipose tissue function.Objectives1) To examine PGF2α release by primary preadipocytes, mature adipocytes and whole tissue explants from the subcutaneous and omental fat compartments; 2) To assess which PGF synthase is the most relevant in human adipose tissue.MethodsFat samples were obtained by surgery in women. PGF2α release by preadipocytes, adipocytes and explants under stimulation by TNF-α, IL-1β or both was measured. Messenger RNA expression levels of AKR1B1 and AKR1C3 were measured by RT-PCR in whole adipose tissue and cytokine-treated preadipocytes. The effect of AKR1B1 inhibitor ponalrestat on PGF2α synthesis was investigated.ResultsPGF2α release was significantly induced in response to cytokines compared to control in omental (p = 0.01) and to a lesser extent in subcutaneous preadipocytes (p = 0.02). Messenger RNA of COX-2 was significantly higher in omental compared to subcutaneous preadipocytes in response to combined TNF-α and IL-1β (p = 0.01). Inflammatory cytokines increased AKR1B1 mRNA expression and protein levels (p≤0.05), but failed to increase expression levels of AKR1C3 in cultured preadipocytes. Accordingly, ponalrestat blunted PGF2α synthesis by preadipocytes in basal and stimulated conditions (p≤0.05). Women with the highest PGF2α release by omental adipocytes had a higher BMI (p = 0.05), waist circumference (p≤0.05) and HOMAir index (p≤0.005) as well as higher mRNA expression of AKR1B1 in omental (p<0.10) and subcutaneous (p≤0.05) adipose tissue compared to women with low omental adipocytes PGF2α release. Positive correlations were observed between mRNA expression of AKR1B1 in both compartments and BMI, waist circumference as well as HOMAir index (p≤0.05 for all).ConclusionPGF2α release by omental mature adipocytes is increased in abdominally obese women. Moreover, COX-2 expression and PGF2α release is particularly responsive to inflammatory stimulation in omental preadipocytes. Yet, blockade of PGF synthase AKR1B1 inhibits most of the PGF2α release.

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“…However, in vivo experiments using cyclo-oxygenase inhibitors showed no appreciable effect of prostaglandins on obesity in man [8], neither did the determinations of PG-E and PG-F plasma levels in fed and starved women [5]. In our experiment we found on Day 2 of fasting, when lipolysis already was stimulated, rather an increase of PG-synthesis.…”

Section: Discussionmentioning

confidence: 64%

Prostaglandin formation and platelet aggregation during fasting and linoleic acid intake

Adam¹,

Wolfram²,

Zöllner³

1985

Res. Exp. Med.

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Prostaglandin formation, estimated by the determination of tetranorprostanedioic acid (TNPDA) in the urine, and platelet aggregation were investigated in seven healthy volunteers each day during fasting, and in three of them additionally during intake of carbohydrates (328kcal/day) or safflor oil (328 kcal, 20 g linoleic acid). Monitoring TNPDA in 8-h fractions of the urine showed a reduction during the night (23.00-07.00) by 70% on the average. During Days 1 and 2 of fasting the amount of TNPDA in 24-h urine was the same as under a conventional diet. On Day 3, TNPDA decreased in all experimental subjects to 162 micrograms/day on the average and was not changed by carbohydrate intake. A linoleic acid intake of 20 g/day increased TNPDA in 24-h urine to pre-experimental levels measured under free diet. Platelet aggregation did not change during the experiment. No relationship between prostaglandin formation and lipolysis in man was found.

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Plasma prostaglandin levels in fed and starved lean, normal and obese women

Cited by 8 publications

References 10 publications

Aggravation by prostaglandin E2 of interleukin-6-dependent insulin resistance in hepatocytes

Aggravation by prostaglandin E2 of interleukin-6-dependent insulin resistance in hepatocytes

Prostaglandin (PG) F2 Alpha Synthesis in Human Subcutaneous and Omental Adipose Tissue: Modulation by Inflammatory Cytokines and Role of the Human Aldose Reductase AKR1B1

Prostaglandin formation and platelet aggregation during fasting and linoleic acid intake

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