23 research outputs found

    Regulation of obesity-associated inflammation and colon tumorigenesis by resveratrol and adiponectin

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    Obesity is characterized by decreased production of the anti-inflammatory hormone, adiponectin, increased secretion of pro-inflammatory cytokines and chemokines, and increased risk of colon cancer. Although adiponectin has been negatively associated with colorectal cancer development in human population, the role of adiponectin in colon tumorigenesis is unknown. The anti-inflammatory dietary polyphenol, resveratrol (RSV), increases circulating adiponectin concentrations in vivo, and has been shown to be effective in prevention of colorectal cancer and obesity-related morbidities. However, the effect of RSV supplementation on obesity-linked colorectal cancer had not been previously reported. We first used an adiponectin knockout mouse model to investigate the role of adiponectin in obesity-associated colorectal cancer. In this study, we showed that in the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced mouse model of colorectal cancer, adiponectin genotype, high fat diet, and gender regulate colon carcinogenesis. Specifically, development of early lesions (aberrant crypt and mucin-depleted foci) was dependent on adiponectin genotype whereas the development of advanced lesions (intramucosal and invasive carcinomas) was dependent on diet and sex of the mice. Interestingly, adiponectin wildtype (Wt) mice had a greater number of total lesions than the knockout (KO) mice suggesting that under pro-inflammatory conditions, the presence of adiponectin promotes colonic tumorigenesis. We next investigated the interaction between RSV and adiponectin in early colon tumorigenesis under obesigenic conditions. In this study, we showed that low-dose dietary RSV (20 mg/kg diet) had a tendency to decrease the number of aberrant crypt foci in Wt but not KO mice. Similarly, RSV had a tendency to reduce circulating pro-inflammatory cytokine and insulin concentrations, prevent adipocyte hypertrophy, and increase lean mass in Wt mice only. Taken together, RSV had a tendency to interact with adiponectin to attenuate tumorigenesis and the metabolic effects of obesity in vivo. We further investigated the interaction between adiponectin and RSV in vitro through the use of adipocytes derived from adiponectin KO and Wt mice and a colon cancer cell line. Here we showed that in adipocytes but not colon cancer cells, the anti-inflammatory effects of RSV are dependent on adiponectin. Finally, we compared the effects of Sirtuin 1 (Sirt1) and AMP-activated protein kinase (AMPK) inhibitors in the attenuation of LPS-induced inflammation by RSV among human adipocyte, monocyte, and colon cancer cell lines. Results obtained from this series of cell culture experiments, suggests that RSV acted through different mechanisms to inhibit chronic LPS-induced inflammation among cell types. In adipocytes, RSV inhibited LPS-induced inflammation and lipolysis, and Sirt1 and AMPK inhibitors reversed this, respectively. In HT29 colon cancer cells, RSV inhibited ROS and proliferation, and the Sirt1 inhibitor, but not the AMPK inhibitor reversed this. Conversely, RSV\u27s inhibition of LPS-induced inflammation in U937 monocytes was not reversed by Sirt1 or AMPK inhibitors. Thus, while Sirt1 appears to be important in the effects of RSV in adipocytes and colon cancer cells, we did not identify a role for Sirt1 or AMPK in RSV\u27s anti-inflammatory action in monocytes. Collectively, our data suggests that adiponectin, diet, and gender interact in the development of obesity-associated colon tumorigenesis under pro-inflammatory conditions. Moreover, we showed that RSV has a tendency to interact with adiponectin to attenuate tumorigenesis and improve the metabolic and inflammatory profile in obesity. These findings support the potential use of RSV as an anti-inflammatory dietary supplement aimed at prevention of obesity-associated colon tumorigenesis through anti-inflammatory function in adipose and colon tissues. Continued research is warranted to further elucidate the role of adiponectin and the cell- and tissue-specific actions of RSV in obesity-associated colon cancer

    Anaplastic large cell lymphoma, ALK-negative

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    Review on Anaplastic large cell lymphoma, ALK-negative, with data on clinics, and the genes involved

    Gestational heat stress alters postnatal offspring body composition indices and metabolic parameters in pigs.

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    The study objectives were to test the hypothesis that heat stress (HS) during gestational development alters postnatal growth, body composition, and biological response to HS conditions in pigs. To investigate this, 14 first parity crossbred gilts were exposed to one of four environmental treatments (TNTN, TNHS, HSTN, or HSHS) during gestation. TNTN and HSHS dams were exposed to thermal neutral (TN, cyclical 18-22°C) or HS conditions (cyclical 28-34°C) during the entire gestation, respectively. Dams assigned to HSTN and TNHS treatments were heat-stressed for the first or second half of gestation, respectively. Postnatal offspring were exposed to one of two thermal environments for an acute (24 h) or chronic (five weeks) duration in either constant TN (21°C) or HS (35°C) environment. Exposure to chronic HS during their growth phase resulted in decreased longissimus dorsi cross-sectional area (LDA) in offspring from HSHS and HSTN treated dams whereas LDA was larger in offspring from dams in TNTN and TNHS conditions. Irrespective of HS during prepubertal postnatal growth, pigs from dams that experienced HS during the first half of gestation (HSHS and HSTN) had increased (13.9%) subcutaneous fat thickness compared to pigs from dams exposed to TN conditions during the first half of gestation. This metabolic repartitioning towards increased fat deposition in pigs from dams heat-stressed during the first half of gestation was accompanied by elevated blood insulin concentrations (33%; P = 0.01). Together, these results demonstrate HS during the first half of gestation altered metabolic and body composition parameters during future development and in biological responses to a subsequent HS challenge

    Heat Stress Reduces Intestinal Barrier Integrity and Favors Intestinal Glucose Transport in Growing Pigs

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    <div><p>Excessive heat exposure reduces intestinal integrity and post-absorptive energetics that can inhibit wellbeing and be fatal. Therefore, our objectives were to examine how acute heat stress (HS) alters intestinal integrity and metabolism in growing pigs. Animals were exposed to either thermal neutral (TN, 21°C; 35–50% humidity; n = 8) or HS conditions (35°C; 24–43% humidity; n = 8) for 24 h. Compared to TN, rectal temperatures in HS pigs increased by 1.6°C and respiration rates by 2-fold (<i>P</i><0.05). As expected, HS decreased feed intake by 53% (<i>P</i><0.05) and body weight (<i>P</i><0.05) compared to TN pigs. Ileum heat shock protein 70 expression increased (<i>P</i><0.05), while intestinal integrity was compromised in the HS pigs (ileum and colon TER decreased; <i>P</i><0.05). Furthermore, HS increased serum endotoxin concentrations (<i>P = </i>0.05). Intestinal permeability was accompanied by an increase in protein expression of myosin light chain kinase (<i>P</i><0.05) and casein kinase II-α (<i>P</i> = 0.06). Protein expression of tight junction (TJ) proteins in the ileum revealed claudin 3 and occludin expression to be increased overall due to HS (<i>P</i><0.05), while there were no differences in claudin 1 expression. Intestinal glucose transport and blood glucose were elevated due to HS (<i>P</i><0.05). This was supported by increased ileum Na<sup>+</sup>/K<sup>+</sup> ATPase activity in HS pigs. SGLT-1 protein expression was unaltered; however, HS increased ileal GLUT-2 protein expression (<i>P = </i>0.06). Altogether, these data indicate that HS reduce intestinal integrity and increase intestinal stress and glucose transport.</p></div