Prostaglandin F2α inhibits adipocyte differentiation via a Gαq‐Calcium‐Calcineurin‐Dependent signaling pathway

Liu, Li; Clipstone, Neil A.

doi:10.1002/jcb.21044

Cited by 87 publications

(80 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We examined mRNA expression of additional genes that are induced or suppressed during adipocyte differentiation. The expression of PPAR␥ is a characteristic of the adipocyte phenotype and the inhibition of adipocyte differentiation reduces PPAR␥ expression (24). Our current findings indicate that PPAR␥ mRNA expression is significantly reduced in epididymal adipose tissue from mice deficient in COX-2 (Fig.…”

Section: Genetic Deficiency Of Cox-2 Reduces Adiposity In Mice-supporting

confidence: 56%

Cyclooxygenase-2 Deficiency Attenuates Adipose Tissue Differentiation and Inflammation in Mice

Ghoshal

Trivedi

Graf

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Obesity is associated with a variety of disorders and is a significant health problem in developed countries. One factor controlling the level of adiposity is the differentiation of cells into adipocytes. Adipocyte differentiation requires expression of peroxisome proliferator-activated receptor ␥ (PPAR␥), which is activated by ligands to regulate expression of genes involved in adipocyte differentiation. Although 15-deoxy-⌬(12,14)-prostaglandin (PG) J 2 (15d-PGJ(2)) has long been known to be a potent activator of PPAR␥, the importance of its synthesis in adipose tissue in vivo is not clear. The current study utilized mice deficient in cyclooxygenase-2 (COX-2) to examine the role of COX-2-derived PGs as in vivo modulators of adiposity. As compared with strain-and age-matched wildtype controls, the genetic deficiency of COX-2 resulted in a significant reduction in total body weight and percent body fat. Although there were no significant differences in food consumption between groups, COX-2-deficient mice showed increased metabolic activity. Epididymal adipose tissue from wild-type mice produced a significantly greater level of 15d-PGJ(2), as compared with adipose tissue isolated from mice deficient in COX-2. Furthermore, production of the precursor required for 15d-PGJ(2) formation, PGD(2), was also significantly reduced in COX-2-deficient adipose tissue. The expression of markers for differentiated adipocytes was significantly reduced in adipose tissue from COX-2-deficient mice, whereas preadipocyte marker expression was increased. Macrophagedependent inflammation was also significantly reduced in adipose tissue of COX-2-deficient mice. These findings suggest that reduced adiposity in COX-2-deficient mice results from attenuated PPAR␥ ligand production and adipocyte differentiation.In developed countries, obesity is a significant health problem that is becoming more prevalent. The increase in adiposity, or the percentage of total body mass comprised of lipid stores, correlates with the development of a variety of disorders including, glucose intolerance, dyslipidemia, and hypertension (1). Recent evidence suggests that in addition to being an energy storage depot, adipose tissue may contribute to disease by producing adipokines, chemokines, and other bioactive substances (2). The level of adiposity is regulated by the amount of lipid taken into individual adipocytes and the number of adipocytes in the body. Adipocyte number is regulated by the differentiation of cells into adipocytes, and understanding this process is important for identifying novel methods for controlling obesity.Adipocyte differentiation requires expression of the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) 2 ␥ (3, 4). When activated by its ligand, PPAR␥ functions as a transcription factor to induce numerous genes involved in adipogenesis. Identification of the endogenous ligand for PPAR␥ has been controversial, but treatment with the prostanoid 15-deoxy-⌬ 12,14 -prostaglandin (PG) J 2 (15d-PGJ 2 ) has long been...

show abstract

Section: Genetic Deficiency Of Cox-2 Reduces Adiposity In Mice-supporting

confidence: 56%

Cyclooxygenase-2 Deficiency Attenuates Adipose Tissue Differentiation and Inflammation in Mice

Ghoshal

Trivedi

Graf

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Thus, it remains uncertain whether 15d-PGJ 2 is truly an endogenous ligand for PPAR ␥ that modulates adipocyte differentiation. Prostaglandin F 2 ␣ (PGF 2 ␣ ) is generated from PGH 2 by PGF 2 ␣ synthase (PGFS), and PGF 2 ␣ is reported to be an inhibitory modulator of adipocyte differentiation ( 12 ). The level of PGF 2 ␣ rapidly increased to a peak 3 h after initiation of differentiation and then declined, indicating that PGF 2 ␣ suppresses in the early phase of adipogenesis ( 13 ).…”

Section: Ptgr-3 Decreases Proadipogenic Effect Of 15-keto-pge 2 Throumentioning

confidence: 99%

Prostaglandin reductase-3 negatively modulates adipogenesis through regulation of PPARγ activity

Chang

et al. 2013

Journal of Lipid Research

View full text Add to dashboard Cite

“…The FP receptor is a Gq-coupled receptor, which once activated leads to release of inositol-1,4,5-trisphosphate and diacylglycerol, which in turn increases the Ca 2 + level (11,13,14). Previous work from others in 3T3-L1 reports that PGF 2a inhibits adipogenesis via a calcineurin-dependent mechanism by blocking expression of critical adipogenic transcription factors PPARc and C/EBPa (15). This mechanism can be negated by calcineurin inhibitors such as cyclosporine and tacrolimus (FK506) (16), which might explain inconsistent results in the management of Graves' orbitopathy (GO) with these agents (17,18).…”

mentioning

confidence: 99%

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Draman

Grennan-Jones²,

Zhang³

et al. 2013

Thyroid

View full text Add to dashboard Cite

Background: In Graves' orbitopathy (GO), increased proliferation, excess adipogenesis, and hyaluronan overproduction produce GO exophthalmos. Enophthalmos occurs in some glaucoma patients treated with Bimatoprost (prostaglandin F 2a , PGF 2a ) eye drops. We hypothesized that enophthalmos is secondary to reductions in orbital tissue proliferation, adipogenesis, and/or increased lipolysis. We aimed to determine which of these is affected by PGF 2a by using the 3T3-L1 murine preadipocyte cell line and primary human orbital fibroblasts (OFs) from GO patients (n = 5) and non-GO (n = 5). Methods: 3T3-L1 cells and orbital OFs were cultured alone or with PGF 2a (all experiments used 10 -8 to 10 -6 M) and counted on days 1/2/3 or 5, respectively; cell cycle analysis (flow cytometry) was applied. Adipogenesis (in the presence/absence of PGF 2a ) was evaluated (day 7 or 15 for 3T3-L1 and primary cells, respectively) morphologically by Oil Red O staining and quantitative polymerase chain reaction measurement of adipogenesis markers (glycerol-3-phosphate dehydrogenase and lipoprotein lipase, respectively). For lipolysis, in vitrodifferentiated 3T3-L1 or mature orbital adipocytes were incubated with norepinephrine and PGF 2a and free glycerol was assayed. Appropriate statistical tests were applied. Results: The population doubling time of 3T3-L1 was 27.3 -1.4 hours-significantly increased by dimethyl sulfoxide 0.02% to 44.6 -4.8 hours ( p = 0.007) and further significantly increased ( p = 0.049 compared with dimethyl sulfoxide) by 10 -8 M PGF 2a to 93.6 -19.0 hours, indicating reduced proliferation, which was caused by prolongation of G2/M. GO OFs proliferated significantly more rapidly than non-GO (population doubling time 5.36 -0.34 or 6.63 -0.35 days, respectively, p = 0.035), but the proliferation of both was significantly reduced (dose dependent from 10 -8 M) by PGF 2a , again with prolongation of G2/M. Adipogenesis in 3T3-L1 cells was minimally affected by PGF 2a when assessed morphologically, but the drug significantly reduced transcripts of the glycerol-3-phosphate dehydrogenase differentiation marker. GO OFs displayed significantly higher adipogenic potential than non-GO, but in both populations, adipogenesis, evaluated by all 3 methods, was significantly reduced (dose dependent from 10 -8 M) by PGF 2a . There was no effect of PGF 2a on basal or norepinephrine-induced lipolysis, in 3T3-L1 or human OFs, either GO or non-GO.Conclusions: The results demonstrate that PGF 2a significantly reduces proliferation and adipogenesis and that human OFs are more sensitive to its effects than 3T3-L1. Consequently, PGF 2a could be effective in the treatment of GO.

show abstract

Prostaglandin F2α inhibits adipocyte differentiation via a Gαq‐Calcium‐Calcineurin‐Dependent signaling pathway

Cited by 87 publications

References 48 publications

Cyclooxygenase-2 Deficiency Attenuates Adipose Tissue Differentiation and Inflammation in Mice

Cyclooxygenase-2 Deficiency Attenuates Adipose Tissue Differentiation and Inflammation in Mice

Prostaglandin reductase-3 negatively modulates adipogenesis through regulation of PPARγ activity

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Contact Info

Product

Resources

About

Prostaglandin F2α inhibits adipocyte differentiation via a Gαq‐Calcium‐Calcineurin‐Dependent signaling pathway

Cited by 87 publications

References 48 publications

Cyclooxygenase-2 Deficiency Attenuates Adipose Tissue Differentiation and Inflammation in Mice

Cyclooxygenase-2 Deficiency Attenuates Adipose Tissue Differentiation and Inflammation in Mice

Prostaglandin reductase-3 negatively modulates adipogenesis through regulation of PPARγ activity

Effects of Prostaglandin F2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Contact Info

Product

Resources

About

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy