The importance of cyclooxygenase 2-mediated oxidative stress in obesity-induced muscular insulin resistance in high-fat-fed rats

Tian, Yufeng; Hsia, Te-Lin; Hsieh, Chang‐Hsun; Huang, Din-Wen; Chen, Chih‐Hao; Hsieh, Po‐Shiuan

doi:10.1016/j.lfs.2011.05.006

Cited by 20 publications

(12 citation statements)

References 33 publications

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“…In fact, after 12 weeks, COX‐2 mediated events may be related to the induction of insulin resistance in a model of high‐fat diet‐induced obesity (Tian et al. ). Previous authors observed an increase in COX‐2 and subsequent insulin resistance in adipose tissue and glycolytic muscles, but not the rat soleus muscle (Tian et al.…”

Section: Discussionmentioning

confidence: 99%

Acute and chronic changes in rat soleus muscle after high-fat high-sucrose diet

et al. 2017

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The effects of obesity on different musculoskeletal tissues are not well understood. The glycolytic quadriceps muscles are compromised with obesity, but due to its high oxidative capacity, the soleus muscle may be protected against obesity‐induced muscle damage. To determine the time–course relationship between a high‐fat/high‐sucrose (HFS) metabolic challenge and soleus muscle integrity, defined as intramuscular fat invasion, fibrosis and molecular alterations over six time points. Male Sprague‐Dawley rats were fed a HFS diet (n = 64) and killed at serial short‐term (3 days, 1 week, 2 weeks, 4 weeks) and long‐term (12 weeks, 28 weeks) time points. Chow‐fed controls (n = 21) were killed at 4, 12, and 28 weeks. At sacrifice, animals were weighed, body composition was calculated (DXA), and soleus muscles were harvested and flash‐frozen. Cytokine and adipokine mRNA levels for soleus muscles were assessed, using RT‐qPCR. Histological assessment of muscle fibrosis and intramuscular fat was conducted, CD68+ cell number was determined using immunohistochemistry, and fiber typing was assessed using myosin heavy chain protein analysis. HFS animals demonstrated significant increases in body fat by 1 week, and this increase in body fat was sustained through 28 weeks on the HFS diet. Short‐term time‐point soleus muscles demonstrated up‐regulated mRNA levels for inflammation, atrophy, and oxidative stress molecules. However, intramuscular fat, fibrosis, and CD68+ cell number were similar to their respective control group at all time points evaluated. Therefore, the oxidative capacity of the soleus may be protective against diet‐induced alterations to muscle integrity. Increasing oxidative capacity of muscles using aerobic exercise may be a beneficial strategy for mitigating obesity‐induced muscle damage, and its consequences.

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Section: Discussionmentioning

confidence: 99%

Acute and chronic changes in rat soleus muscle after high-fat high-sucrose diet

et al. 2017

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“…Hsieh et al (8)(9)(10) reported muscle and fat IR improved in rats fed fructose or a high-fat diet (HFD) treated with COX-2 inhibitors. However, Coll et al (11) found that COX-2 inhibition exacerbated palmitate-induced inflammation and IR in skeletal muscle.…”

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confidence: 99%

Hepatic Cyclooxygenase-2 Expression Protects Against Diet-Induced Steatosis, Obesity, and Insulin Resistance

et al. 2014

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Accumulation evidence links obesity-induced inflammation as an important contributor to the development of insulin resistance, which plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes and nonalcoholic fatty liver disease. Cyclooxygenase (COX)-1 and -2 catalyze the first step in prostanoid biosynthesis. Because adult hepatocytes fail to induce COX-2 expression regardless of the proinflammatory stimuli used, we have evaluated whether this lack of expression under mild proinflammatory conditions might constitute a permissive condition for the onset of insulin resistance. Our results show that constitutive expression of human COX-2 (hCOX-2) in hepatocytes protects against adiposity, inflammation, and, hence, insulin resistance induced by a high-fat diet, as demonstrated by decreased hepatic steatosis, adiposity, plasmatic and hepatic triglycerides and free fatty acids, increased adiponectin-to-leptin ratio, and decreased levels of proinflammatory cytokines, together with an enhancement of insulin sensitivity and glucose tolerance. Furthermore, hCOX-2 transgenic mice exhibited increased whole-body energy expenditure due in part by induction of thermogenesis and fatty acid oxidation. The analysis of hepatic insulin signaling revealed an increase in insulin receptor-mediated Akt phosphorylation in hCOX-2 transgenic mice. In conclusion, our results point to COX-2 as a potential therapeutic target against obesity-associated metabolic dysfunction.Insulin resistance (IR) plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes and nonalcoholic fatty liver disease. IR is the key primary defect underlying the development of type 2 diabetes and is a central component defining the metabolic syndrome. That IR is associated with a state of chronic low-grade inflammation has been demonstrated, and inflammation is assumed to contribute in a major way to its development (1). Besides the fact that IR is characterized by complex interactions between genetic determinants and nutritional factors, it is recognized that mediators synthesized from immune cells and adipocytes are involved in the regulation of insulin action (2). Insulin acts in target cells by binding to its specific receptor and activating a cascade of intracellular signaling events that are altered in inflammation-associated IR (3).Inflammation induces the expression of a variety of proteins, including prostaglandin-endoperoxide synthase-2, also known as cyclooxygenase (COX)-2, which catalyzes the first step in prostanoid biosynthesis. COX-2 is induced by a variety of stimuli such as growth factors, proinflammatory mediators, hormones, and other cellular

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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

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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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The importance of cyclooxygenase 2-mediated oxidative stress in obesity-induced muscular insulin resistance in high-fat-fed rats

Cited by 20 publications

References 33 publications

Acute and chronic changes in rat soleus muscle after high-fat high-sucrose diet

Acute and chronic changes in rat soleus muscle after high-fat high-sucrose diet

Hepatic Cyclooxygenase-2 Expression Protects Against Diet-Induced Steatosis, Obesity, and Insulin Resistance

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

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