Caloric restriction, physical exercise, and CB1 receptor blockade as an efficient combined strategy for bodyweight control and cardiometabolic status improvement in male rats

Obesity is critically associated with the development of insulin resistance and related cardiovascular and kidney diseases. Several strategies for weight loss have been developed but most of them exhibit a post-intervention rebound effect. Here, we aimed to design combined weight-loss strategies of caloric restriction, physical exercise, and administration of a CB1 receptor blocker to inhibit food intake that also accomplish the objectives of lost-weight maintenance and improvement of cardiovascular and renal function. Diet-induced obesity (DIO) was generated in Sprague Dawley rats for 12 weeks to test the effects of single or combined strategies (i.e. caloric restriction, mixed training protocol, and/or administration of appetite suppressant) on caloric intake, body weight, cardiovascular and renal functionality resulting from a weight-loss intervention period of 3 weeks followed by 6 weeks of weight maintenance. Consumption of a high-fat diet (HFD) caused a significant increase in body weight (5th week of the experimental period) and led to the development of insulin resistance, cardiovascular, and renal alterations. The different interventions tested, resulted in a significant body weight loss and improved glucose metabolism, aerobic capacity, electrocardiographic parameters, vascular expression of adhesion molecules and inflammatory mediators, and renal functionality, reaching values similar to the control normocaloric group or even improving them. Successful maintenance of lost weight was achieved along a 6-week maintenance period in addition to adequate health status. In conclusion, the weight-loss and maintenance intervention strategies tested were efficient at reversing the obesity-related alterations in body weight, glucose metabolism, aerobic capacity, cardiovascular and renal functionality. The beneficial action was very consistent for caloric restriction and physical exercise, whereas administration of a CB1 receptor blocker complemented the effects of the prior interventions in some parameters like body weight or aerobic capacity, and showed specific actions in renal status, increasing glomerular filtration rate and diuresis. Overall, the novelty of our study relies on the easy implementation of combined strategies for effective weight management that resulted in significant health benefits.Spanish Ministry of Science, Innovation and UniversitiesEuropean Commission DEP2014-58296-R RTC-2017-6540-1 RTI2018-100934-B-I00European Commissio

Anemonia sulcata and Its Symbiont Symbiodinium as a Source of Anti-Tumor and Anti-Oxoxidant Compounds for Colon Cancer Therapy: A Preliminary in Vitro Study

Simple Summary: Colorectal cancer is one of the most frequent types of cancer in the population. Recently, invertebrate marine animals have been investigated for the presence of natural products which can damage tumor cells, prevent their spread to other tissues or avoid cancer develop. We analyzed the anemone Anemonia sulcata with and without the presence of its microalgal symbiont (Symbiodinium) as a source of bioactive molecules for the colorectal cancer therapy and prevention. Colon cancer tumor cells were exposed to Anemone extracts observing a remarkable cell death and a great antioxidant capacity. These preliminary results support that Anemonia sulcata could be a source of bioactive compounds against colorectal cancer and that the absence of its symbiont may enhance these properties. Further studies will be necessary to define the bioactive compounds of Anemonia sulcata and their mechanisms of action. Abstract: Recently, invertebrate marine species have been investigated for the presence of natural products with antitumor activity. We analyzed the invertebrate Anemonia sulcata with (W) and without (W/O) the presence of its microalgal symbiont Symbiodinium as a source of bioactive compounds that may be applied in the therapy and/or prevention of colorectal cancer (CRC). Animals were mechanically homogenized and subjected to ethanolic extraction. The proximate composition and fatty acid profile were determined. In addition, an in vitro digestion was performed to study the potentially dialyzable fraction. The antioxidant and antitumor activity of the samples and the digestion products were analyzed in CRC cells in vitro. Our results show a high concentration of polyunsaturated fatty acid in the anemone and a great antioxidant capacity, which demonstrated the ability to prevent cell death and a high antitumor activity of the crude homogenates against CRC cells and multicellular tumor spheroids, especially W/O symbiont. These preliminary results support that Anemonia sulcata could be a source of bioactive compounds with antioxidant and antitumor potential against CRC and that the absence of its symbiont may enhance these properties. Further studies will be necessary to define the bioactive compounds of Anemonia sulcata and their mechanisms of action.International Excellence Campus of the Sea (CEI.MAR) CEIJ-007 CEIJ-001

Bioavailability and biotransformation of linolenic acid from basil seed oil as a novel source of omega-3 fatty acids tested on a rat experimental model

Basil is an aromatic herb with a high concentration of bioactive compounds. The oil extracted from its seeds is a good source of α-linolenic acid (ALA) and also provides substantial amounts of linoleic acid (LA). This study aimed to test the bioavailability of the oil derived from basil seeds and its effects on different physiological parameters using 7–15% dietary inclusion levels. Furthermore, the assimilation of LA and ALA and their transformation in long-chain polyunsaturated fatty acids (LC-PUFAs) have been studied. Digestive utilization of total fat from basil seed oil (BSO) was high and similar to that of olive oil used as a control. Consumption of BSO resulted in increased LA and ALA levels of the plasma, liver, and erythrocyte membrane. In addition, the transformation of LA to arachidonic acid (ARA) was decreased by the high dietary intake of ALA which redirected the pathway of the Δ-6 desaturase enzyme towards the transformation of ALA into eicosapentaenoic acid (EPA). No alterations of hematological and plasma biochemical parameters were found for the 7 and 10% dietary inclusion levels of BSO, whereas a decrease in the platelet count and an increase in total- and HDL-cholesterol as well as plasma alkaline phosphatase (ALP) were found for a 15% BSO dose. In conclusion, BSO is a good source of ALA to be transformed into EPA and decrease the precursor of the pro-inflammatory molecule ARA. This effect on the levels of EPA in different tissues offers potential for its use as a dietary supplement, novel functional food, or a constituent of nutraceutical formulations to treat different pathologies.Spanish GovernmentEuropean Commission PTQ-17-09172 RTC-2017-6540-1 RTI2018-100934-B-I00 RTC2019-006870-1Andalusian Government AGR145 CTS164 CTS-10

Novel insights and mechanisms of diet-induced obesity: Mid-term versus long-term effects on hepatic transcriptome and antioxidant capacity in Sprague-Dawley rats

Supplementary data to this article can be found online at https://doi.org/10.1016/j.lfs.2023.121746Aims The study of molecular mechanisms related to obesity and associated pathologies like type 2-diabetes and non-alcoholic fatty liver disease requires animal experimental models in which the type of obesogenic diet and length of the experimental period to induce obesity deeply affect the metabolic alterations. Therefore, this study aimed to test the influence of aging along a rat model of diet-induced obesity in gene expression of the hepatic transcriptome. Main methods A high-fat/high-fructose diet to induce obesity was used. Mid- (13 weeks) and long-term (21 weeks) periods were established. Caloric intake, bodyweight, hepatic fat, fatty acid profile, histological changes, antioxidant activity, and complete transcriptome were analyzed. Key findings Excess bodyweight, hepatic steatosis and altered lipid histology, modifications in liver antioxidant activity, and dysregulated expression of transcripts related to cell structure, glucose & lipid metabolism, antioxidant & detoxifying capacity were found. Modifications in obese and control rats were accounted for by the different lengths of the experimental period studied. Significance Main mechanisms of hepatic fat accumulation were de novo lipogenesis or altered fatty acid catabolism for mid- or long-term study, respectively. Therefore, the choice of obesity-induction length is a key factor in the model of obesity used as a control for each specific experimental design.Spanish Ministry of Science and Innovation, and the European Union through projects B-AGR-662-UGR20, RTI-2018-100934-B-I00, and the FEDER program, respectivel

Antitumor Effect of the Ethanolic Extract from Seeds of Euphorbia lathyris in Colorectal Cancer

The seeds of Euphorbia lathyris have been used in traditional medicine to treat various medical conditions. However, neither all of their active biocompounds nor the molecular mechanisms underlying their therapeutic effects have been described. A new ethanolic extract of defatted flour from mature seeds of Euphorbia lathyris showed a high total polyphenol content and significant antioxidant activity. Chromatographic analysis showed that esculetin, euphorbetin, gaultherin, and kaempferol-3-rutinoside were the most abundant polyphenolic bioactive compounds. Antiproliferative assays showed a high and selective antitumor activity against colon cancer cell lines (T84 and HCT-15). In addition, a significant antiproliferative activity against glioblastoma multiforme cells was also demonstrated. Its mechanism of action to induce cell death was mediated by the overexpression of caspases 9, 3, and 8, and by activation of autophagy. Interestingly, a reduction in the migration capacity of colon cancer cells and a significant antiangiogenic effect on human umbilical vein endothelial cells were also demonstrated. Finally, the extract significantly reduced the subpopulations of cancer stem cells. This extract could be the basis to develop new therapeutic strategies for the treatment of colon cancer, although further experiments will be necessary to determine its in vivo effects.Granada University (project PSE/17/002), Ministerio de Ciencia e Innovación (project RTC-2017-6540-1) and by the CTS-107 and AGR145 Groups

Aerobic interval exercise improves parameters of Non Alcoholic Fatty Liver Disease (NAFLD) and other alterations of metabolic syndrome in obese Zucker rats.

Metabolic syndrome (MS) is a group of metabolic alterations that increase the susceptibility to cardiovascular disease and type 2 diabetes. Nonalcoholic fatty liver disease has been described as the liver manifestation of MS. We aimed to test the beneficial effects of an aerobic interval training (AIT) protocol on different biochemical, microscopic, and functional liver alterations related to the MS in the experimental model of obese Zucker rat. Two groups of lean and obese animals (6 weeks old) followed a protocol of AIT (4 min at 65%-80% of maximal oxygen uptake, followed by 3 min at 50%-65% of maximal oxygen uptake for 45-60 min, 5 days/week, 8 weeks of experimental period), whereas 2 control groups remained sedentary. Obese rats had higher food intake and body weight (P < 0.0001) and suffered significant alterations in plasma lipid profile, area under the curve after oral glucose overload (P < 0.0001), liver histology and functionality, and antioxidant status. The AIT protocol reduced the severity of alterations related to glucose and lipid metabolism and increased the liver protein expression of PPARγ, as well as the gene expression of glutathione peroxidase 4 (P < 0.001). The training protocol also showed significant effects on the activity of hepatic antioxidant enzymes, although this action was greatly influenced by rat phenotype. The present data suggest that AIT protocol is a feasible strategy to improve some of the plasma and liver alterations featured by the MS

MOOC como herramienta para el aprendizaje de contenidos específicos en el área de la Fisiología

Teniendo en cuenta que el aprendizaje integral y la implementación de las TICs están cada vez más integradas en el sistema educativo, la creación de “cápsulas educativas”-MOOCs son una herramienta creativa que puede ayudar al alumnado en la asimilación de los conocimientos. Además, al ser una herramienta de duración corta les obliga resumir la información, destacar la más importante y ser capaces de trasmitirla. Para ello, el objetivo principal de esta propuesta de innovación docente ha sido elaborar una nueva herramienta docente y aplicarla en el área de Fisiología, en concreto en la asignatura de Fisiología Celular y Humana del Grado en Farmacia. Para ello se formaron diferentes grupos de estudiantes a los que les asignó una temática relacionada con el área de Fisiología y dos tutores (participantes en el equipo de investigación) que los han acompañado en la creación de MOOC. Por otro lado, se creó el grupo de evaluadores externos, responsables para la evaluación de la capsula educativa definitiva. Para facilitar el desarrollo del proyecto, antes del comienzo del proyecto se elaboraron y se consensuaron las rúbricas necesarias para evaluar el proceso de la creación de MOOC por parte de los tutores y evaluadores. La comunicación entre los grupos de estudiantes y de los miembros del equipo de investigación se ha realizado usando el correo electrónico y con documentos compartidos en la nube de la UGR. Las diferentes tutorías entre los tutores asignados y los grupos de los alumnos, se han realizado por Google Meet. La nota final de las capsulas educativas, ha sido resultado de la interacción tanto del equipo de tutores como de evaluadores externos. Al final del proceso se ha hecho una exposición de las capsulas educativas en la clase con los demás compañeros. Al finalizar el proceso, se ha utilizado la plataforma de Google Forms para recibir las opiniones de los estudiantes y recoger sus propuestas. Según las opiniones manifestadas, la iniciativa de aplicar esta herramienta en el área de Fisiología ha recibido muy buenas críticas sobre todo sobre la innovación de la propuesta. El alumnado por otro lado destacó que le gustaría encontrar esta herramienta en otras asignaturas. Sin embargo, también mencionaron que les gustaría saber algo más sobre aplicaciones disponibles para elaborar los videos y poder ser aún más creativos. Por último, se usará la plataforma zenodo para la difusión y divulgación de los trabajos creados para que los demás estudiantes puedan consultarlos. Los resultados de esta propuesta se publicarán en congresos docentes nacionales e internacionales con el objetivo de compartir la experiencia con otros docentes e intentar implementar esta herramienta en asignaturas de áreas afines.Considering that comprehensive learning and the implementation of ICTs are increasingly integrated into the educational system, the creation of "educational capsules"-MOOCs are a creative tool that can help students assimilate knowledge. In addition, having a limited duration forces them to summarize the information, highlight the most important and be able to transmit it. For this, the main objective of this teaching proposal was the development of a new teaching tool and apply it in Physiology, specifically in the subject of Cellular and Human Physiology of the Degree in Pharmacy. For this, different groups of students were formed and a specific subject was assigned to them, related to the area of Physiology. Moreover, two tutors (member of the research team) were assigned to each group and have accompanied them in the creation of MOOCs. On the other hand, the group of external evaluators, responsible for the evaluation of the educational capsule, was created. To facilitate the development of the project, prior to the beginning of the project, the necessary rubrics were prepared and discussed between the different members, to be able to evaluate the process of creating MOOCs by both the tutors and evaluators. Communication between the student groups and the members of the research team was maintained using emails and documents were shared in the UGR cloud. The meetings between the assigned tutors and the student groups have been carried out through Google Meet. The grade of the educational capsules has resulted as the median of tutors as well the external evaluators. Once created, MOOCs were presented in the rest of the classroom with the other classmates. At the end of the process, the Google Forms platform has been used to fulfil a questionnaire and collect the opinions of the students and collect their proposals for future improvements. According to the opinions expressed, the initiative to apply this tool in the Physiology area has received very good reviews by the students, especially regarding the innovation of the proposal. The students, on the other hand, highlighted that they would like to be able to use this tool in other subjects of their carreer. However, they also mentioned that they would like to know more about available applications to make videos, a fact that would help them be even more creative. Finally, the zenodo platform will be used for the dissemination of the works created so that other students can consult them. The results of this proposal will be published in national and international teaching conferences with the aim of sharing the experience with other teachers and trying to implement this tool in subjects in related areas.Universidad de Granad