RETRACTED: Obesity-Induced Increase in Tumor Necrosis Factor-α Leads to Development of Colon Cancer in Mice

Flores, Marcelo B.S.; Rocha, Guilherme Z.; Damas-Souza, Danilo Marchete; Osório–Costa, Felipe; Dias, Milton; Ropelle, Eduardo Rochete; Camargo, Juliana Alves de; Carvalho, Rita Barbosa de; Carvalho, Hernandes F.; Saad, Mário José Abdalla; Carvalheira, José B.C.

doi:10.1053/j.gastro.2012.05.045

Cited by 65 publications

(58 citation statements)

References 42 publications

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“…We show here that IL-6 is increased in the polyps with HFD feedings, although this did not quite reach statistical significance. Lastly, mRNA expression of TNF-α was measured in the adipose tissue and tumor microenvironment as it has been reported to increase with obesity and has been linked with pro-tumoral processes [36]. While, we did not detect any changes in adipose tissue TNF-α expression with this diet, it was increased in the polyp tissue.…”

Section: Discussionmentioning

confidence: 57%

Linking inflammation to tumorigenesis in a mouse model of high-fat-diet-enhanced colon cancer

et al. 2013

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Many observational epidemiologic studies suggest an association between high-fat-diet (HFD) and colon cancer risk. However, the lack of controlled experimental studies that examine this relationship and the mechanisms involved weaken the basis for inferring a causal relationship. Inflammation plays a role in colon cancer progression and HFDs have been reported to increase inflammation; however, the inflammatory effects of HFD in colon cancer have yet to be firmly established. We examined the effects of a novel HFD that closely mimics the standard American diet (12% and 40% of total caloric intake from saturated fat and total fat, respectively) on macrophage markers and inflammatory mediators in a mouse model of intestinal tumorigenesis and relate this to polyp characteristics as well as measures of adiposity. Male ApcMin/+ mice (7–8/group) were fed a Control Diet (Con) or novel high-fat-diet (HFD) from 4 to 12 weeks of age. Body weight and body composition were measured weekly and monthly, respectively. Intestinal tissue was analyzed for polyp burden (number and size). Gene expression of macrophage markers and inflammatory mediators were examined in the adipose tissue and polyps. The HFD increased the expression of macrophage markers and inflammatory mediators in the adipose tissue (F4/80, CD11c, TLR-4 and MCP-1) and tumor microenvironment (IL-12, MCP-1, IL-6 and TNF-α). As expected, the HFD increased body weight, body fat percent, fat mass and blood glucose (P < 0.05), and was associated with an increase in the number of large polyps (P < 0.05) but not total polyps. In summary, consumption of a HFD, similar in macronutrient composition to the standard American diet, altered the expression of macrophage phenotypic markers and inflammatory mediators in adipose tissue and intestinal polyps and this was associated with increased tumorigenesis.

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Section: Discussionmentioning

confidence: 57%

Linking inflammation to tumorigenesis in a mouse model of high-fat-diet-enhanced colon cancer

et al. 2013

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“…TNF-a is known to promote colon cancer (Flores et al, 2012) and is associated with human irritable bowel disease and colitis (Natsui et al, 1997). Resveratrol is reported to reduce TNF-a in colon cancer cell lines (Paul et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Role of microRNAs in Resveratrol-Mediated Mitigation of Colitis-Associated Tumorigenesis inApc^Min/+Mice

Altamemi

Murphy

Catroppo

et al. 2014

J Pharmacol Exp Ther

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The pleiotropic effects of resveratrol include anti-inflammatory, antioxidant, and anticancer activities, and thus unique possibilities exist to explore mechanistic pathways of chemoprevention. The aim of this study was to investigate the role of microRNA (miRNA) alterations induced by resveratrol in the context of chemopreventive mechanisms against dextran sodium sulfate (DSS)-induced colitis-associated tumorigenesis in the Apc Min/1 mouse. To that end, ApcMin/1 mice were exposed to 2% DSS to enhance intestinal inflammation and polyp development. Concurrently, mice received either vehicle or resveratrol treatment via oral gavage for 5 weeks. Interestingly, treatment of DSS-exposed mice with resveratrol resulted in decreased number and size of polyps, fewer histologic signs of cell damage, and decreased proliferating epithelial cells in intestinal mucosa compared with vehicle. Resveratrol treatment dramatically reversed the effects of DSS on the numbers of specific inflammatory CD4 1 T cells, CD8 1 T cells, B cells, natural killer T cells, and myeloid-derived suppressor cells in mesenteric lymph nodes. Resveratrol treatment also decreased interleukin-6 (IL-6) and tumor necrosis factor-a protein levels and reduced IL-6 and cyclooxygenase-2 mRNA expression. Microarray analysis revealed 104 miRNAs exhibiting .1.5-fold differences in expression in the intestinal tissue of resveratrol-treated mice. Among them, two miRNAs with anti-inflammatory properties, miRNA-101b and miRNA-455, were validated to be upregulated with resveratrol treatment by reverse-transcription polymerase chain reaction. Pathway analysis revealed that numerous differentially regulated miRNAs targeted mRNAs associated with inflammatory processes with known roles in intestinal tumorigenesis. These results suggest that resveratrol mediates anti-inflammatory properties and suppresses intestinal tumorigenesis through miRNA modulation.

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“…It is known to be rich in polyphenolics such as rutin, quercetin, and 1-deoxynojirimycin (DNJ). Therefore, it has been used in traditional medicine to treat several metabolic diseases including dyslipidemia (Azman et al 2012), diabetes (Flores et al 2012), fatty liver disease (Ou et al 2011), and hypertension (Kobayashi et al 2006). The mulberry leaf also enhances antioxidant enzyme activities in diabetic rats (Ha et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Mulberry leaves (Morus alba L.) ameliorate obesity-induced hepatic lipogenesis, fibrosis, and oxidative stress in high-fat diet-fed mice

2015

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Obesity is associated with chronic diseases such as fatty liver, type 2 diabetes, cardiovascular disease, and severe metabolic syndrome. Obesity causes metabolic impairment including excessive lipid accumulation and fibrosis in the hepatic tissue as well as the increase in oxidative stress. In order to investigate the effect of mulberry leaf (Morus alba L.) extract (MLE) on obesity-induced oxidative stress, lipogenesis, and fibrosis in liver, MLE has been gavaged for 12 weeks in high-fat diet (HFD)-induced obese mice. MLE treatment significantly ameliorated LXRa-mediated lipogenesis and hepatic fibrosis markers such as a-smooth muscle actin, while MLE up-regulated lipolysis-associated markers such as lipoprotein lipase in the HFD-fed mice. Moreover, MLE normalized the activities of antioxidant enzymes including heme oxygenase-1 and glutathione peroxidase in accordance with protein levels of 4-hydroxynonenal in the HFDfed mice. MLE has beneficial effects on obesity-related fatty liver disease by regulation of hepatic lipid metabolism, fibrosis, and antioxidant defense system. MLE supplementation might be a potential therapeutic approach for obesity-related disease including non-alcoholic fatty liver disease.

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RETRACTED: Obesity-Induced Increase in Tumor Necrosis Factor-α Leads to Development of Colon Cancer in Mice

Cited by 65 publications

References 42 publications

Linking inflammation to tumorigenesis in a mouse model of high-fat-diet-enhanced colon cancer

Linking inflammation to tumorigenesis in a mouse model of high-fat-diet-enhanced colon cancer

Role of microRNAs in Resveratrol-Mediated Mitigation of Colitis-Associated Tumorigenesis inApc^Min/+Mice

Mulberry leaves (Morus alba L.) ameliorate obesity-induced hepatic lipogenesis, fibrosis, and oxidative stress in high-fat diet-fed mice

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RETRACTED: Obesity-Induced Increase in Tumor Necrosis Factor-α Leads to Development of Colon Cancer in Mice

Cited by 65 publications

References 42 publications

Linking inflammation to tumorigenesis in a mouse model of high-fat-diet-enhanced colon cancer

Linking inflammation to tumorigenesis in a mouse model of high-fat-diet-enhanced colon cancer

Role of microRNAs in Resveratrol-Mediated Mitigation of Colitis-Associated Tumorigenesis inApcMin/+Mice

Mulberry leaves (Morus alba L.) ameliorate obesity-induced hepatic lipogenesis, fibrosis, and oxidative stress in high-fat diet-fed mice

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Role of microRNAs in Resveratrol-Mediated Mitigation of Colitis-Associated Tumorigenesis inApc^Min/+Mice