Comparison of PGE2, prostacyclin and leptin release by human adipocytes versus explants of adipose tissue in primary culture

Fain, John N.; Kanu, Alie; Bahouth, Suleiman W.; Cowan, George S M; Hiler, Magdalena; Leffler, Charles W.

doi:10.1054/plef.2002.0430

Cited by 51 publications

(42 citation statements)

References 27 publications

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“…Previously, we examined the release of PGE 2 , IL-8, IL-6, plasminogen activator inhibitor (PAI-1), hepatocyte growth factor (HGF), IL-10, TNFa, vascular endothelial growth factor (VEGF) A and IL-1b by explants of visceral adipose tissue from women with similar BMI values. 17,18 The release over 48 h of MCP-1 reported here was Regulation of MCP-1 release JN Fain and AK Madan comparable to that of PAI-1 and IL-6 but less than that of IL-8 or PGE 2 . 17 MCP-1 release by adipocytes as % of that by the nonfat cells of adipose tissue was 9%, which is comparable to that for PGE 2 , IL-8, IL-6, PAI-1, HGF, IL-10, TNFa, VEGF A and IL-1b under similar conditions.…”

Section: Discussionmentioning

confidence: 57%

“…PGE 2 was determined by radioimmunoassay as previously described. 18 Bovine serum albumin powder (Bovuminar, containing o0.05 mol of fatty acid/mole of albumin) was obtained from Intergen (Purchase, NY, USA). Bacterial collagenase Results MCP-1 release was examined after 2, 24 or 48-h incubation in primary culture using cut pieces of visceral adipose tissue.…”

Section: Methodsmentioning

confidence: 99%

“…PGE 2 release was also examined as a comparison marker since it is involved in the inflammatory response and is released as a result of cyclooxygenase 2 (COX-2) upregulation during in vitro incubation of human subcutaneous adipose tissue explants. 17,18 The release of PGE 2 by human adipose tissue is primarily due to the nonfat cells that accounted for 93% of total release over a 48-h incubation by the fractions obtained after collagenase digestion of human adipose tissue. 17,18 We wanted to see if the release of MCP-1 is also by the nonfat cells.…”

Section: Introductionmentioning

confidence: 99%

“…17,18 The release of PGE 2 by human adipose tissue is primarily due to the nonfat cells that accounted for 93% of total release over a 48-h incubation by the fractions obtained after collagenase digestion of human adipose tissue. 17,18 We wanted to see if the release of MCP-1 is also by the nonfat cells. Furthermore, it has been reported that COX products serve as endogenous repressors of MCP-1 formation in experimental glomerulonephritis.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Fain

Madan

2005

Int J Obes

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BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment during inflammation whose plasma level is elevated in obesity. OBJECTIVE: The present studies were designed to examine the release of MCP-1 in primary culture by explants of visceral adipose tissue from morbidly obese women. RESULTS: Most of the MCP-1 released by adipose tissue explants was derived from the nonfat cells in adipose tissue. The release of MCP-1 by adipose tissue explants was upregulated almost five-fold between 3 and 48 h of incubation. Approximately half of this upregulation was due to the release of endogenous tumor necrosis factor a (TNFa) and IL-1b based on the ability of a combination of a soluble TNFa receptor (etanercept) and a blocking antibody against IL-1b to reduce MCP-1 release. The release of MCP-1 over 48 h was unaffected by insulin or dexamethasone but significantly reduced by the combination of both agents. MCP-1 release was reduced by 60% in the presence of an inhibitor of the nuclear factor kB (NF-kB) pathway. There were no significant effects of inhibitors of p44/42 mitogen-activated protein kinase (ERK), Jun N-terminal kinase (JNK) and p38 mitogenactivated protein kinase (p38 MAPK) pathways on MCP-1 release. However, inhibition of MCP-1 release in the presence of inhibitors of both the p38 MAPK and NF-kB pathways was greater than that seen with only the NF-kB inhibitor. DISCUSSION: The present data shows that MCP-1 formation is upregulated over a 48-h incubation of primary explants of visceral adipose tissue. Half of this upregulation is dependent upon endogenous TNFa and Il-1b and involves the p38 MAPK and NF-kB pathways.

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Section: Discussionmentioning

confidence: 57%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Fain

Madan

2005

Int J Obes

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“…24 The pH of the buffer was adjusted to 7.4 and then filtered through a 0.2 mm filter. Interleukin-8 (IL-8), leptin and adiponectin release to the medium were determined using an ELISA assay with Duoset reagents from R&D Systems of Minneapolis, MN.…”

Section: Methodsmentioning

confidence: 99%

Regulation of adiponectin release and demonstration of adiponectin mRNA as well as release by the non-fat cells of human omental adipose tissue

et al. 2007

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Objective: Adiponectin is an adipokine produced by adipose tissue. The present studies examined the in vitro release of adiponectin by human omental adipose tissue explants as well as the mRNA content of freshly isolated non-fat cells and adipocytes plus cultured preadipocytes and adipocytes derived from omental fat. Results: The release of adiponectin was reduced while that of interleukin-8 (IL-8) was enhanced in tissue explants from morbidly obese women. The release of adiponectin was also reduced by one-third in explants from morbidly obese diabetic women while that of IL-8 was unaffected by diabetes. The release of adiponectin was enhanced by insulin and by inhibition of endogenous tumor necrosis factor (TNFa) using etancercept. Adiponectin was released in appreciable amounts by the undigested matrix obtained by collagenase digestion of adipose tissue. The release of adiponectin by non-fat cells (matrix þ SV cells) was comparable to that by the adipocytes derived from the same amount of tissue while the adiponectin mRNA content of the pooled matrix and SV cell fractions was 40% of that in intact tissue. The adiponectin mRNA content was 48-fold greater in isolated adipocytes than in non-fat cells derived from adipose tissue. In contrast, the amount of adiponectin mRNA in vitro differentiated omental adipocytes was 1 Â l0 6 -fold greater than that in cultured preadipocytes while that of leptin was 3 Â 10 4 -fold greater. Conclusion: Adiponectin mRNA is present in the non-fat cells of freshly isolated adipose tissue and release by the non-fat cells derived from a gram of adipose tissue is comparable to that by adipocytes isolated from the same amount of tissue. While leptin is only released by mature adipocytes, adiponectin is released by both the non-fat cells and the fat cells derived from human omental adipose tissue.

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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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Comparison of PGE2, prostacyclin and leptin release by human adipocytes versus explants of adipose tissue in primary culture

Cited by 51 publications

References 27 publications

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Regulation of adiponectin release and demonstration of adiponectin mRNA as well as release by the non-fat cells of human omental adipose tissue

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

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