Suppressive effect of COX2 inhibitor on the progression of adipose inflammation in high‐fat‐induced obese rats

Hsieh, Po‐Shiuan; Lu, Kun; Chiang, Chih-Fan; Chen, C.-H.

doi:10.1111/j.1365-2362.2009.02239.x

Cited by 54 publications

(39 citation statements)

References 26 publications

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“…Other studies provide evidence that PGE 2 might suppress de novo lipogenesis. The work of Hsieh et al (47)(48)(49) showed that rats fed with a fructose or high-fat diet and treated with COX-2 inhibitors improve muscle and fat insulin resistance. However, contradictory results were obtained by Coll et al, who showed that COX-2 inhibition exacerbated palmitate-induced inflammation and IR in skeletal muscle (50).…”

Section: Discussionmentioning

confidence: 99%

Regulation of MicroRNA 183 by Cyclooxygenase 2 in Liver Is DEAD-Box Helicase p68 (DDX5) Dependent: Role in Insulin Signaling

Motiño

Francés

Mayoral

et al. 2015

Molecular and Cellular Biology

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g Cyclooxygenase (COX) catalyzes the first step in prostanoid biosynthesis and exists as two isoforms. COX-1 is a constitutive enzyme involved in physiological processes, whereas COX-2 is induced by a variety of stimuli. MicroRNAs (miRNAs) are noncoding RNAs that function as key posttranscriptional regulators of gene expression. Although it is known that COX-2 expression is regulated by miRNAs, there are no data regarding COX-2 involvement in miRNA regulation. Considering our previous results showing that COX-2 expression in hepatocytes protects against insulin resistance, we evaluated the role of COX-2 in the regulation of a specific set of miRNAs implicated in insulin signaling in liver cells. Our results provide evidence of the molecular basis for a novel function of COX-2 in miRNA processing. COX-2 represses miRNA 23b (miR-23b), miR-146b, and miR-183 expression in liver cells by increasing the level of DEAD-box helicase p68 (DDX5) through phosphatidylinositol 3-kinase (PI3K)/p300 signaling and by modulating the enzymatic function of the Drosha (RNase type III) complex through its physical association with DDX5. The decrease of miR-183 expression promotes protection against insulin resistance by increasing insulin receptor substrate 1 (IRS1) levels. These results indicate that the modulation of miRNA processing by COX-2 is a key event in insulin signaling in liver and has potential clinical implications for the management of various hepatic dysfunctions. Cyclooxygenase 1 (COX-1) and 2 catalyze the first step in prostanoid biosynthesis. COX-1 (PTGS1) is constitutively expressed in many tissues, whereas COX-2 (PTGS2) expression is induced by a variety of stimuli such as growth factors, proinflammatory stimuli, hormones, and other cellular stresses (1-3). We and others have demonstrated that partial hepatectomy (PH) induced COX-2 expression in hepatocytes and contributed to the progression of the cell cycle during regeneration (4, 5). In addition to liver regeneration after PH or exposure to hepatotoxic agents, expression of COX-2 has been detected in animal models of cirrhosis (6), in human hepatoma cell lines (7,8), in human hepatocellular carcinoma (HCC) (9), and after hepatitis B virus (HBV) and hepatitis C virus (HCV) infection (10, 11). Further, overexpression of COX-2 in liver exerts efficient protection against acute liver injury by an antiapoptotic/antinecrotic effect and by accelerated early hepatocyte proliferation (12, 13).Insulin resistance (IR) plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Our previous results from studies performed in a model of transgenic mice constitutively expressing human COX-2 in hepatocytes (hCOX-2-Tg) indicate a protective role of COX-2 in a model of insulin resistance induced by a high-fat diet (HFD) (14) and in liver damage induced by hyperglycemia (15).MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate their target genes primarily through RNA destabilization or t...

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Section: Discussionmentioning

confidence: 99%

Regulation of MicroRNA 183 by Cyclooxygenase 2 in Liver Is DEAD-Box Helicase p68 (DDX5) Dependent: Role in Insulin Signaling

Motiño

Francés

Mayoral

et al. 2015

Molecular and Cellular Biology

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“…Prostaglandin E2 acts on EP3 receptors to decrease lipolysis by decreasing cAMP concentration and, thereby, contributes to the hypertrophic development of adipocyte (Jaworski et al, 2009). In addition, it has been demonstrated that cyclooxygenase (COX)-2 mediated inflammation in fat plays a pivotal role in the development of adipose tissue inflammation, insulin resistance and fatty liver in high fat-induced obese rats (Hsieh et al, 2009(Hsieh et al, , 2010. The time-dependent increases in plasma insulin, glucose, leptin levels and homeostasis model assessment of insulin resistance (HOMA-IR) shown in high-fat induced obese rats were significantly reversed in those co-treated with a selective COX2 inhibitor (Celecoxib or Mesulid).…”

Section: Inflammatory Fatty Acidsmentioning

confidence: 99%

“…The time-dependent increases in plasma insulin, glucose, leptin levels and homeostasis model assessment of insulin resistance (HOMA-IR) shown in high-fat induced obese rats were significantly reversed in those co-treated with a selective COX2 inhibitor (Celecoxib or Mesulid). COX2 inhibition also significantly reversed adipocyte hypertrophy, macrophage infiltration and decreased in markers of adipocyte differentiation shown in high fat diet-induced obese rats, especially in visceral fat rather than those in subcutaneous fat (Hsieh et al, 2009(Hsieh et al, , 2010. In addition, in the COX2 deficient mouse model, PPAR-gamma (an adipocyte differentiation marker) mRNA expression in epididymal adipose tissue was reduced (Ghoshal et al, 2010).…”

Section: Inflammatory Fatty Acidsmentioning

confidence: 99%

“…Selective COX2 inhibitors may improve obesity-associated adipose tissue abnormalities (Hsieh et al, 2009(Hsieh et al, , 2010. Besides COX inhibiton, salicylates also act through inhibition of the activity of inhibitor of nuclear factor kappa-B kinase subunit beta (IKK-) leading to a reduction in translocation of NF-kB to the nucleus, which action is crucially involved in the anti-diabetic effect of aspirin (Yin et al, 1998;Yuan et al, 2001).…”

Section: Salicylates and Cox2 Inhibitorsmentioning

confidence: 99%

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Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance

Hsieh¹

2011

Role of the Adipocyte in Development of Type 2 Diabetes

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“…The PGH 2 that is produced is metabolized into different PG's that are involved in adipocyte differentiation which causes the activation of PPARγ (Ueno et al, 2011;Ghoshal et al, 2011). Therefore, bearing this expression mechanism in mind-the inhibition of COX-2 would prevent or decrease the conversion of archadionic acid to PGH 2 which will have the ultimate effect of reducing and/or inhibiting adipocyte differentiation.COX-2 activation has also been found to be significantly involved in development of an inflammatory response in adipose tissue (Hsieh et al, 2010) and has been linked to contributing in brown adipocyte differentiation in mice (Ghoshal et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Effects of Caffeine, Paracetamol and Βnaphthoflavone on the Lipid Content and Differentiation of Human Adipose Derived Mesenchymal Stem Cells in Vitro

Companioni¹,

Faroun²,

Metwalli³

et al. 2018

Preprint

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Obesity is a complex multifactorial disorder involving the differentiation of pre-adipocytes to mature adipocytes which is achieved through the process of adipogenesis via interaction with different adipogenic transcription factors and mediators. Many drugs and their interactions has been implicated with the common feature of adipose tissue enlargement through hyperplasia and hypertrophy. Caffeine and Paracetamol are few of the most common used drugs which have been theorized by previous researches to have some influence on the adipogenic process. In our study, we investigated the effects of Caffeine, Paracetamol and β-Naphthoflavone on the differentiation of Human Adipose Derived Mesenchymal Stem Cells (HAD-MSC). Cells were cultured in vitro using differentiation inducing media with and without the presence of different combinations of the drugs. Biochemical markers of adipogenesis were evaluated using biochemical assays for triglyceride and glycerol quantification. Our results show that there is an increase of glycerol and triglyceride concentration in cells treated with caffeine suggesting its anti-lipogenesis characteristics through the enhancement of the lipolytic process.Paracetamol also appears to have anti-adipogenic effects due to its apparent role in suppressing the accumulation of triglycerides. In addition, only the use of β-Naphthoflavone in combination with caffeine and Paracetamol, resulted in lower triglyceride concentrations than the latter two drugs alone which may indicate its possible enhancing anti-adipogenic properties is through its interaction with the other two drugs.

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Suppressive effect of COX2 inhibitor on the progression of adipose inflammation in high‐fat‐induced obese rats

Abstract: Our findings suggest that COX2 activation is crucially involved in the development of inflammatory response in adipose tissues of high-fat-induced obese rats.

Cited by 54 publications

References 26 publications

Regulation of MicroRNA 183 by Cyclooxygenase 2 in Liver Is DEAD-Box Helicase p68 (DDX5) Dependent: Role in Insulin Signaling

Regulation of MicroRNA 183 by Cyclooxygenase 2 in Liver Is DEAD-Box Helicase p68 (DDX5) Dependent: Role in Insulin Signaling

Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance

Effects of Caffeine, Paracetamol and Βnaphthoflavone on the Lipid Content and Differentiation of Human Adipose Derived Mesenchymal Stem Cells in Vitro

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