Effects of the combination of biomolecules present in foodstuffs, conjugated linoleic acid, resveratrol and quercetin, on body fat accumulation

322 p.Dada la creciente incidencia de obesidad a nivel mundial, el presente trabajo deinvestigación se ha centrado en la búsqueda de biomoléculas activas presentes en losalimentos, las cuales han demostrado poseer cierta actividad reductora de la grasacorporal, con el objetivo de potenciar su efecto al ser administradas en combinación.Las moléculas objeto de estudio de esta tesis, el Ácido Linoléico Conjugado (CLA), elResveratrol (RSV) y la Quercetina (Q), han sido administradas en un modelo animal derata Wistar alimentado con una dieta obesogénica comercial.En líneas generales, se han analizado los efectos de dos combinaciones (RSV+CLA yRSV+Q) sobre la acumulación de la grasa corporal de los animales tratados. Por ello,esta tesis se ha centrado fundamentalmente en los efectos y mecanismos de acciónjustificativos de los efectos observados en el tejido adiposo blanco, si bien cabemencionar que se han realizado mediciones en otros órganos y tejidos como elhígado, músculo, suero y tejido adiposo marrón.Los resultados de la presente investigación revelan que la combinación de RSV+CLAno resulta una herramienta útil para tratar la obesidad puesto que los efectosreductores de la grasa corporal ejercidos por cada molécula cuando éstas sonadministradas de forma individual desaparecen al ser co-administradas. Por elcontrario, la administración conjunta de RSV+Q no solo produce un efecto sinérgicoen la reducción de la grasa corporal sino que además induce una marronización deltejido adiposo blanco (efecto no descrito previamente para estas biomoléculas) yreduce la esteatosis hepática. Es por ello que esta última combinación resulta unapropuesta útil de ser considerada para el tratamiento y/o prevención de la obesidad

Changes in white adipose tissue metabolism induced by resveratrol in rats

Background: A remarkable range of biological functions have been ascribed to resveratrol. Recently, this polyphenol has been shown to have body fat lowering effects. The aim of the present study was to assess some of the potential underlying mechanisms of action which take place in adipose tissue. Methods: Sixteen male Sprague-Dawley rats were randomly divided into two groups: control and treated with 30 mg resveratrol/kg body weight/d. All rats were fed an obesogenic diet and after six weeks of treatment white adipose tissues were dissected. Lipoprotein lipase activity was assessed by fluorimetry, acetyl-CoA carboxylase by radiometry, and malic enzyme, glucose-6P-dehydrogenase and fatty acid synthase by spectrophotometry. Gene expression levels of acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase, hormone-sensitive lipase, adipose triglyceride lipase, PPAR-gamma, SREBP-1c and perilipin were assessed by Real time RT-PCR. The amount of resveratrol metabolites in adipose tissue was measured by chromatography. Results: There was no difference in the final body weight of the rats; however, adipose tissues were significantly decreased in the resveratrol-treated group. Resveratrol reduced the activity of lipogenic enzymes, as well as that of heparin-releasable lipoprotein lipase. Moreover, a significant reduction was induced by this polyphenol in hormone-sensitive lipase mRNA levels. No significant changes were observed in other genes. Total amount of resveratrol metabolites in adipose tissue was 2.66 +/- 0.55 nmol/g tissue. Conclusions: It can be proposed that the body fat-lowering effect of resveratrol is mediated, at least in part, by a reduction in fatty acid uptake from circulating triacylglycerols and also in de novo lipogenesis.This study was supported by grants from the Ministerio de Ciencia e Innovacion (AGL2008-1005-ALI and partially by the AGL2006-14228-C03-02), Instituto de Salud Carlos III (RETIC PREDIMED) and the Government of Pais Vasco (IT-386-10; CTP09/R5). G. Alberdi is a recipient of a doctoral fellowship from the Ministerio de Ciencia e Innovacion. Resveratrol was a generous gift from Monteloeder (Elche, Alicante, Spain)

Effects of the combination of biomolecules present in foodstuffs, conjugated linoleic acid, resveratrol and quercetin, on body fat accumulation

322 p.Dada la creciente incidencia de obesidad a nivel mundial, el presente trabajo deinvestigación se ha centrado en la búsqueda de biomoléculas activas presentes en losalimentos, las cuales han demostrado poseer cierta actividad reductora de la grasacorporal, con el objetivo de potenciar su efecto al ser administradas en combinación.Las moléculas objeto de estudio de esta tesis, el Ácido Linoléico Conjugado (CLA), elResveratrol (RSV) y la Quercetina (Q), han sido administradas en un modelo animal derata Wistar alimentado con una dieta obesogénica comercial.En líneas generales, se han analizado los efectos de dos combinaciones (RSV+CLA yRSV+Q) sobre la acumulación de la grasa corporal de los animales tratados. Por ello,esta tesis se ha centrado fundamentalmente en los efectos y mecanismos de acciónjustificativos de los efectos observados en el tejido adiposo blanco, si bien cabemencionar que se han realizado mediciones en otros órganos y tejidos como elhígado, músculo, suero y tejido adiposo marrón.Los resultados de la presente investigación revelan que la combinación de RSV+CLAno resulta una herramienta útil para tratar la obesidad puesto que los efectosreductores de la grasa corporal ejercidos por cada molécula cuando éstas sonadministradas de forma individual desaparecen al ser co-administradas. Por elcontrario, la administración conjunta de RSV+Q no solo produce un efecto sinérgicoen la reducción de la grasa corporal sino que además induce una marronización deltejido adiposo blanco (efecto no descrito previamente para estas biomoléculas) yreduce la esteatosis hepática. Es por ello que esta última combinación resulta unapropuesta útil de ser considerada para el tratamiento y/o prevención de la obesidad

Resveratrol: Anti-Obesity Mechanisms of Action

Resveratrol is a non-flavonoid polyphenol which belongs to the stilbenes group and is produced naturally in several plants in response to injury or fungal attack. Resveratrol has been recently reported as preventing obesity. The present review aims to compile the evidence concerning the potential mechanisms of action which underlie the anti-obesity effects of resveratrol, obtained either in cultured cells lines and animal models. Published studies demonstrate that resveratrol has an anti-adipogenic effect. A good consensus concerning the involvement of a down-regulation of C/EBPa and PPAR. in this effect has been reached. Also, in vitro studies have demonstrated that resveratrol can increase apoptosis in mature adipocytes. Furthermore, different metabolic pathways involved in triacylglycerol metabolism in white adipose tissue have been shown to be targets for resveratrol. Both the inhibition of de novo lipogenesis and adipose tissue fatty acid uptake mediated by lipoprotein lipase play a role in explaining the reduction in body fat which resveratrol induces. As far as lipolysis is concerned, although this compound per se seems to be unable to induce lipolysis, it increases lipid mobilization stimulated by beta-adrenergic agents. The increase in brown adipose tissue thermogenesis, and consequently the associated energy dissipation, can contribute to explaining the body-fat lowering effect of resveratrol. In addition to its effects on adipose tissue, resveratrol can also acts on other organs and tissues. Thus, it increases mitochondriogenesis and consequently fatty acid oxidation in skeletal muscle and liver. This effect can also contribute to the body-fat lowering effect of this molecule.This study was supported by grants from Ministerio de Economia y Competitividad (AGL2011-27406-ALI), Instituto de Salud Carlos III (CIBERobn), and University of the Basque Country (UPV/EHU) (IT-572-13 and ELDUNANOTEK UFI11/32)

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research