A study published in the prestigious Cell Metabolism journal and led by the Diabetes and
Associated Metabolic Diseases (DIAMET) research group of the Pere Virgili Health Research
Institute (IIPSV) and linked to the Joan XXIII University Hospital of Tarragona, has made it
possible to discover the mechanism through which adipocytes (the cells that primarily compose
adipose tissue) produce leptin, one of the main hormones that regulates appetite. It has also
been identified that this new mechanism regulates the biological clock of fat cells. In fact, today
it is known that adipocytes have their own internal clock (independent of external factors such
as light), which is essential for adipose tissue to perform its functions correctly.
The historical discovery of leptin as a hormone secreted by adipocytes in the 1990s led to a
paradigm shift, as it showed that the body fat must be considered an active endocrine organ
that regulates satiety and body weight. From that moment, even though numerous scientific
papers have studied how leptin acts in the central nervous system (it inhibits the intake by
producing the feeling of satiety) and why in obese people this mechanism does not work
correctly, no significant advances had been made regarding the production process of this
hormone in adipose tissue.
This research, which has received more than one million euros from the Fundación “la Caixa”
and from the Agencia Estatal de Investigación (Ministerio de Ciencia e Innovación), represents a very significant milestone not only from the physiological point of view (since it helps to improve
understanding of the biological processes that control body weight), but also for addressing
metabolic diseases such as obesity.
In the words of Sonia Fernández-Veledo, researcher at the IIPSV and head of DIAMET: “If
everything works correctly, when we eat, the levels of leptin in the blood increase. This hormone
is responsible for sending the satiety signal to our brain. Obese people produce more leptin than
thin people, but in turn, a phenomenon known as leptin resistance develops, which means that
the body does not respond to this hormone. Therefore, people with obesity have the mechanism
of satiety altered. Our study not only demonstrates the mechanism by which adipocytes produce
leptin, but also why obese people’s fat does so excessively.”
According to the World Health Organization (WHO), more than one billion people worldwide are
obese, data that continues an upward trend. WHO also warns that obesity is directly associated
with type 2 diabetes, cardiovascular diseases and those related to mental health, hypertension,
stroke and various forms of cancer.
Succinate, key in this process
Succinate, an energetic metabolite that can also act as a hormone through its SUCNR1 receptor,
plays a very important role in all these processes. The DIAMET group is an international
benchmark in the study of this metabolite in the context of inflammatory and metabolic diseases
(such as obesity and diabetes). For many years, a mainly inflammatory role has been attributed
to this metabolite, in addition to being identified as a biomarker of metabolic dysfunction in
diseases such as obesity and diabetes (in this type of patients its levels are chronically elevated).
However, in recent years, the DIAMET group has shown that this is a complex system, since
succinate levels also increase (although transiently) in some physiological situations, such as
when we eat food.
In the words of Sonia Fernández-Veledo: “It is in this context where we believe that succinate –
through its receptor SUCNR1- naturally regulates energy homeostasis, that is, the internal
functions of our organism that control the balance between energy intake and its expenditure.
In this study we demonstrated that one of the mechanisms is through the production of leptin
and, therefore, through the feeling of satiety, but we anticipate that it will have other
physiological functions acting on other tissues. In addition, we demonstrate that succinate
would determine leptin oscillations throughout the day by controlling the biological clock of adipocytes. In obese people, this mechanism is hyperactivated, which would partly explain the
elevated leptin levels.”
This scientific advance represents a turning point in the treatment of obesity and opens the
doors to future studies aimed at investigating not only other metabolic functions of succinate,
but also at exploring therapies that allow restoring this mechanism, thus achieving that its levels,
as well like those of the hormone leptin, can be stabilized and it can recover its role in regulating
the feeling of satiety.
The study has received funding from the CaixaResearch Health Research Call (Fundación ”la
Caixa”) and from the Agencia Estatal de Investigación (Ministerio de Ciencia e Innovación). It has
been possible thanks to the joint effort and commitment of several institutions: the Centro de
Investigación Biomédica en Red – Diabetes y Enfermedades Metabólicas (CIBERDEM), the CIBER
de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), the Centres de Recerca de Catalunya
(CERCA), the Rovira i Virgili University, Joan XXIII University Hospital of Tarragona, the Instituto
de Investigaciones Biomédicas Alberto Sols, the Institut d’Investigació Biomèdica de Bellvitge
(IDIBELL), the Institut d’Investigacions Biomèdiques (IBI) Sant Pau, the Universitat Autònoma de
Barcelona (UAB), the Institut d’Investigació Biomèdica de Girona (IDIBGI), the Universitat de
Girona and the Universitat de Barcelona.
Bibliographic reference: SUCNR1 signaling in adipocytes controls energy metabolism by
modulating circadian clock and leptin expression. Villanueva-Carmona T, Cedó l, Madeira A,
Ceperuelo-Mallafré V, Rodríguez-Peña M-M, Núñez-Roa C, Maymó-Masip E, Repollés-De-
Dalmau E, Badia J, Keiran N, Mirasierra M, Pimenta-Lopes C, Sabadell-Basallote J, Bosch R,
Caubet L , Carles Escolà-Gil J, Fernandez-Real JM, Vilarrasa N, Ventura F, Vallejo M, Vendrell J,
Fernández-Veledo S. 2023, Cell Metabolism 35, 1–19 April 4, 2023.
https://doi.org/10.1016/j.cmet.2023.03.004
The more than 10 years of work by researchers from the Pere Virgili Health Research Institute (IISPV) and the Rovira i Virgili University (URV) in the field of diabetic retinopathy (a very common eye condition in people with diabetes of type 2) has recently crystallized in the constitution of the spin-off RetinaReadRisk, in which different partners take part. The spin-off company will market software and a mobile system based on artificial intelligence to detect and treat this pathology in the early stages.
In Catalonia, the test to detect diabetic retinopathy (consists of examining the fundus of the eye with a non-mydriatic camera) is carried out in certain primary care centers (CAP), mostly located in cities. Precisely, one of the objectives of the spin-off is to integrate this mobile system and the computer programs developed with the help of artificial intelligence to the entire Catalan public health system, so that people can be explored by their doctor without the need for commute.
To make it possible, this project will be submitted to a call by the Department of Health of the Generalitat de Catalunya that selects the most innovative technological solutions to integrate them into the public network of primary care centers. On the other side, the fact that the spin-off RetinaReadRisk has been created within the framework of an EIT Health program (which is part of the European Institute of Innovation and Technology -EIT-, a body of the European Union that co-finances the homonymous project, RetinaReadRisk) expands its business opportunities to other territories and countries.
GENESIS Biomed has acted as a Venture Building platform, has invested in the spin-off through its investment vehicle (GENESIS Tech Transfer Boost) and is currently assuming the duties of interim CEO of the company. In the words of Josep Lluís Falcó, CEO of GENESIS Biomed: “We are facing a huge opportunity that can change the paradigm of diabetic patient management, anticipating their potential evolution towards diabetic retinopathy. We offer a powerful tool that will end up leading to significant savings for the national health system.”
Artificial intelligence in health
“The research carried out in recent years by the IISPV and the URV in the fields of diabetic retinopathy and artificial intelligence led to the development of two software: Mira, which allows a reading to be carried out automatic of the images of the fundus of the patient’s eye and which, therefore, will identify whether or not diabetic retinopathy exists; and a second software, the Retiprogram, which, based on a series of clinical and personal data, determines the risk of a person with type 2 diabetes of suffering from diabetic retinopathy, in addition to calculating when the next control must be carried out”, explains Pere Romero, researcher in charge of the Ophthalmology Research Group of the IISPV.
The basis of the Mira program is Deep Learning: thousands of images are taken of the fundus of the patient’s eye, and these are labeled according to the degree of evolution of diabetic retinopathy. In this way, the software developed by the URV team analyzes these thousands of images with the help of artificial intelligence, learns to distinguish the various degrees of retinopathy and classifies them based on the patterns it identifies “so that, once new images of patients have been analyzed, a reliable diagnosis can be made based on this previous training”, points out Domènec Puig, researcher in the ITAKA group of the Department of Computer Engineering and Mathematics of the URV and co-founder of UP2Smart, the spin-off of the university which is also one of the member societies of RetinaReadRisk. “Within the framework of the project financed by EIT Health, work is being done on the integration of these two software in a compact and easy-to-use mobile system”, he adds.
Entrepreneurial initiatives like those of RetinaReadRisk are key to addressing diseases with a high incidence in our society in a more efficient and personalized way. Diabetic retinopathy is a very common condition of the retina in people who suffer from type 2 diabetes (25% of the population in Spain has this type of diabetes). Failure to detect and treat it in the early stages can have significant health consequences, such as a deterioration of night vision that prevents driving or such as blindness (in the case of developing countries).
About the RetinaReadRisk spin-off and the founding partners
RetinaReadRisk
The partners who founded this spin-off are: IISPV, GENESIS Biomed, UP2Smart (URV) and Grupo TRC (Telefónica). The new spin-off RetinaReadRisk hopes to attract private and public funding in the next 2-3 years for an approximate amount of 5 million euros to be able to finalize the development of the product and commercialize it.
GENESIS Biomed
GENESIS Biomed is a consultancy firm that operates in the biomedical sector and is specialized in the provision of services to newly formed companies mainly from universities, research centers, hospitals and technology centers. GENESIS Biomed is headquartered in Barcelona and it also has offices in Madrid.
IISPV
The Pere Virgili Health Research Institute is an institution of international prestige that brings together biomedical research led from Camp de Tarragona and the Terres de l’Ebre. It includes the University Hospital of Tarragona Joan XXIII; the Hospital of Tortosa Verge de la Cinta; the Sant Joan University Hospital, in Reus; and the Pere Mata Group. Rovira i Virgili University is also linked to it.
UP2Smart
UP2Smart is an spin-off company from the URV. It is dedicated, among others, to offering automatic and embedded systems based on computer vision and artificial intelligence; and to provide technological products and services for industrial and business sectors. For illustrative purposes, but not limiting, UP2Smart is also dedicated to offering consulting services, technological advice, software and app development, user support and web solutions.
Grupo TRC
Grupo TRC has its TRC Health division backed by more than 25 years of work in hospital networks. The uniqueness of the solutions developed, as well as the high level of demand and criticality of the systems and software used, make it possible to complete a broad technological portfolio based on experience and innovation. The objective of this division is the development of systems that improve hospital processes, with high levels of security and reliability, guaranteeing profitability, and agility and ease of management.
EIT Health
EIT Health is a network of best-in-class health innovators with approximately 130 partners and is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union. It collaborates across borders to deliver new solutions that can enable European citizens to live longer, healthier lives. It connects all relevant healthcare players across European borders – making sure to include all sides of the “knowledge triangle”, so that innovation can happen at the intersection of research, education and business for the benefit of citizens.
An investigation led from the IISPV has concluded, involving 1,800 mothers and their sons and daughters, of pre-school age
A study led by the Institut d’Investigació Sanitària Pere Virgili (IISPV), in Tarragona, has made it possible to observe for the first time that eating too many ultra-processed foods (such as suffocated drinks or potatoes) during pregnancy affects the children’s linguistic and verbal capabilities. It is the result of a pioneering research in this field around the world, which sheds light on this key aspect of childhood development and learning and further demonstrates the role of diet in people’s health.
In order to carry out this research, which is an initiative of the IISPV NeuroÈpia Research Group (with the collaboration of ISGlobal, a centre promoted by the Fundació “la Caixa”, and other institutions, such as the Universitat Rovira i Virgili and the Centro de Investigación Biomédica en Red), a representative sample of the population of Spain consisting of 1,800 mothers and their respective sons and daughters has been studied for four years (from 2004 to 2008). Children have been tracked from the time of birth and up to 5 years (pre-school age), when language skills such as verbal reasoning and agility or numerical memory are developed.
Jordi Júlvez, who is responsible for this research group, explains with some examples what these concepts mean and what implications they have for children’s health: “some examples of linguistic skills are learning how to relate verbal concepts that are similar by completing sentences to the infant of the type a cat and a dog are… The answer is mammals. We are also talking about verbal fluidity, which could be expressed by being able to name the child or child, for 20 seconds, names of different fruits”. And he adds: “In any society, country… Some people eat healthy food and some do not. That is why we opted to do a population study, with mothers and children with more and less healthy eating habits, to reflect this diversity. Thanks to this approach, the results and conclusions can be applied to any child in this age range”.
Social class and economy, other key aspects
To assess the development of these children, the internationally recognized McCarthy scale has been used. One of the most important categories of mental fitness that includes their tests is that of linguistic skills, which, along with nonverbal or visual and perceptual abilities (thanks to which we learn how to manipulate materials or elements; how to coordinate our body; and how to develop nonverbal reasoning) determine the degree of overall cognition that the child achieves. Hence, the diet’s affection for children in this area of their development is key.
Júlia Puig, a nutritionist and public health professional of the IsGlobal research group, explains the criteria set for assessing whether the intake of ultra-processed foods in the diet of mothers who have been part of the study was elevated: “When they were accepted into the study, they were first asked to answer a food consumption questionnaire. To assess whether their diet contained a high load of ultra-processed food, we divided them into three equal groups: one in which mothers with a low intake level of ultra-processed, one with a medium level and one high. We saw that the children of mothers who were part of the high level earned a low score to verbal skills in the McCarthy test. It is important to know that the profile of a mother in this group was that of a woman with primary, low social class and not normally following a Mediterranean diet. Taking these aspects into account offers a more global view of this reality”.
Bibliography Reference: Puig-Vallverdú J, Romaguera D, Fernández-Barrés S, Gignac F, Ibarluzea J, Santa-Maria L, Llop S, Gonzalez S, Vioque J, Riaño-Galán I, Fernández-Tardón G, Pinar A, Turner MC, Arija V, Salas-Savadó J, Vrijheid M, Julvez J. The association between maternal ultra-processed food consumption during pregnancy and child neuropsychological development: A population-based birth cohort study. Clin Nutr. 2022 Oct;41(10):2275-2283. doi: 10.1016/j.clnu.2022.08.005. Epub 2022 Aug 19. PMID: 36087519.
Listen to the interview (48′ 38″- 49′ 37″) with Jordi Júlvez, to “El món a RAC1” (October 14, 2022).
In Spain, 25% of the population either has diabetes or is in a previous or early stage of the disease, according to the Di@bet.es study, led by CIBERDEM and financed by the Instituto de Salud Carlos III[1]. As the incidence is growing in recent years, the Ophthal-mology Research Group of the Institut d’Investigació Sanitària Pere Virgili (IISPV) and ITAKA Group (Intelligent Technologies for Advanced Knowledge Acquisition), from the Universitat Rovira i Virgili (URV), have developed a software and a system based on artificial intelligence to diagnose the diabetic retinopathy, a common eye disorder in patients with type 2 diabetes, which is the leading cause of low vision in adults between 50 and 70 years of age in the Western world, and one of the main causes of blindness in the Third World (the higher prevalence being linked with a large number of infections). A timely treatment is crucial to prevent the diabetic retinopathy from progressing since “it’s a silent and an asymptomatic disease, which means that when the patient goes to the doctor it is often too late”, explains Pere Romero, head of both the IISPV Ophthalmology research group and this service at the Hospital Universitari Sant Joan de Reus and tenured professor at the URV.
Currently, the National Health System in Spain includes an annual examination of the fundus of the eye for each patient with diabetes. This test is carried out in hospitals with the help of a retinography. However, in the real life, these medical centers are not ac-cessible for everyone (in Catalonia, for example, 5% of the population lives in rural are-as, and this percentage is continuously increasing). Hence, these researchers have de-veloped a mobile system in collaboration with several partners (Telefónica and TRC), so that it is the general practitioner who takes the necessary photograph for this examina-tion. Through an automatic reading system, he can determine whether or not the patient suffers from retinopathy.
If so, the doctor, by previously entering the patient’s data into a system based on artifi-cial intelligence, will be able to know when the next check-up should be carried out. In this way, the patient can have a more exhaustive control of the disease. These tests with the new mobile system will soon begin to be carried out in some primary care centers in rural areas of Catalonia.
“We have developed two algorithms, one for automatic image reading, which makes it possible to identify whether or not there is diabetic retinopathy and what type. This helps primary care physician to treat patients. The second algorithm is a diagnostic aid system –RETIPROGRAM– which, based on a series of parameters, determines the diabetic patient’s risk of suffering from diabetic retinopathy, in addition to calculating when the next control should be carried out”, adds Pere Romero.
The professor of the Department of Computer Engineering and Mathematics of the URV, Domènec Puig (and also an IISPV researcher in this project) is another important actor since his team is the one in charge of developing the artificial intelligence algorithms: “We saw the possibility of linking computation with retinal image analysis to automate screening by using computer vision methods. Automating means being able to guide decisions to help diagnose, that is, to implement algorithms that offer the doctor a help, to facilitate his work”, explains. And he stresses: “We are not talking in any case of re-placing the specialist doctor”.
The basis of this computing system is Deep Learning: thousands of images of the pa-tient’s eye fundus are taken and labelled according to the degree of evolution of diabetic retinopathy. In this way, the software developed by this team analyzes thousands of images with the help of artificial intelligence, learns from these cases and classifies them based on the patterns it identifies “because when new images arrive, a diagnosis can be made based on that training process”, explains Domènec Puig. And he underlines: “the broader that training is, the more reliable the system is”.
This project has received support from the Fondo de Investigaciones Sanitarias (FIS), granted by the Instituto de Salud Carlos III. In 2021, a RetinaReadDisk consortium was created with the participation of seven partners: Telefónica SA, Grupo TRC, Genesis Biomed, the Institut Català de la Salut, the Institut d’Investigació Sanitària Pere Virgili and the French organizations Fondation de l’Avenir and E’Seniors. Thanks to these syn-ergies, the project has been able to access the financial support network of EIT Health, an organization supported by the European Union.
Given that until now the images have been obtained using a retinograph, the challenge now facing these researchers is to retrain and adapt the system so that it is sensitive to the images obtained through this new mobile device.
This technological breakthrough illustrates the potential of personalized medicine (also referred to as precision medicine). This device will be marketed in France and Spain in the first place with the intention of expanding its marketing in South America as well.
[1] In this interview, on Ràdio Ciutat de Tarragona, Sonia Fernández-Veledo, principal investigator of the DIAMET group (Diabetes and associated metabolic diseases) of the IISPV delves into these data: https://www.alacarta.cat/noticies-en-xarxa- edicio-cap-de-setmana-radio/capitol/nex__mati_cap_de_setmana_12062022 (33′ 51” – 38′ 14”)
Thanks to the combined efforts of the Pere Virgili Health Research Institute (IISPV) and the University of Cambridge, it will be possible to tackle metabolic and inflammatory diseases (such as obesity and diabetes) from a global perspective. Researchers from both institutions will work together to study the inflammation in the central nervous system that these diseases cause and how this leads to an alteration of the intake patterns (the desire to eat or the fact of feeling satiated, for example) and the development of insulin resistance, among other aspects.
Combining efforts in this field of research is key, given that the number of people with diabetes and obesity is growing significantly year after year. The World Health Organization recalls that, in the last 5 decades, the percentage of the world’s population with obesity has tripled. Moreover, in Spain, 25% of the population either has diabetes or is in a previous or initial state of the disease, according to the Di@bet.es study, led by CIBERDEM and financed by the Instituto de Salud Carlos III.
The Diabetes and Associated Metabolic Diseases (DIAMET) research group of the IISPV has made remarkable findings in recent years, published in prestigious scientific journals, regarding the role of succinate (a metabolite whose blood levels appear elevated in patients with obesity and diabetes) in the inflammation of peripheral organs such as adipose tissue or the liver. The University of Cambridge stands out for its research work in the field of neuroinflammation, that is, the inflammatory processes produced in the central nervous system and in the context of diseases such as multiple sclerosis.
Bring together expertise and research
Doctor Sonia Fernández-Veledo is the principal researcher of this project, entitled NEUROinflammatory role of the succinate/SUCNR1 axis in obesity-related DIAbetes (NEURO_DIA), and funded by the European Foundation for the Study of Diabetes through the Novo Nordisk A/S Program for Diabetes Research in Europe. She is a consolidated researcher (R4) at the IISPV, where she leads the Diabetes and Metabolic Associated Diseases Research Group (DIAMET). She has been acknowledged as coIP of the group in CIBERDEM. Her research combines basic and clinical studies to shed light on the molecular mechanisms underlying comorbidities related to obesity, which may contribute to find new approaches and aims for the treatment of these metabolic diseases. In this project, Sonia Fernández-Veledo will work in collaboration with the researcher from the University of Cambridge, Luca Peruzzotti-Jametti, whose investigative line focuses on studying the mechanisms that trigger chronic damage in the nervous central system in a context of neuroinflammation. His most recent work is setting the stage for a new series of interventions that target cell metabolism in immune cells, as the next opportunity to promote the healing of the persistently inflamed central nervous system.
The project, entitled Science Engagement to Empower aDolescentS (SEEDS), is carried out by researchers from IISPV-CERCA and the URV and aims to reduce the time young people spend in front of screens and contribute to acquire healthier habits by increasing physical activity and improving their diet
Contributing to the acquisition of healthier lifestyles by young people when it comes to eating or practicing physical activity is one of the major challenges of the World Health Organization (WHO), according to different studies published by the institution in recent years. Faced with this scenario, researchers from the Institut d’Investigació Sanitària Pere Virgili (IISPV)-CERCA and the Rovira i Virgili University (URV) have led a European project, entitled Science Engagement to Empower aDolescentS (SEEDS), which in Spain has had the participation of different state high schools in the province of Tarragona. More than 225 second and third year ESO students from these schools have taken part throughout 2021-2022.
The SEEDS initiative has been carried out in collaboration with different European partners: The University of Exeter (UOE); Charokopeio Panepistimio (HUA); The European Citizen Science Association (ECSA); City of Rotterdam (COR) and Erasmus Universitair Medisch Centrum Rotterdam (EMC). The project is funded by the Horizon 2020 programme of the European Commision and also aims to arouse the interest of adolescents in the professions called STEM (careers in science, technology, engineering and mathematics). These careers are increasingly in demand in the labour market but are also professions where gender bias is very evident. In Europe, only 1 out of 3 girls consider focusing their studies towards these professions, while in the case of boys this proportion is 3 times higher.
Citizens participate in research
According to the research team that led the project, “a key point in changing the facts and society is to reverse these figures”. Therefore, the SEEDS project has been carried out based on Citizen Science, a type of Participatory Research which consists of actively involving citizens (adolescents, in this case) in research. An additional goal is to put science at the service of social transformation, which is why researchers from the local government of the City of Rotterdam plus local stakeholders are involved. Thus, it was the same students from these state high schools in Tarragona who decided on some of the life habits needed to be improved, working in collaboration with local stakeholders, and how to do it all by proposing different actions. Some of the ones that were eventually carried out are: nutrition workshops aimed at the boys and girls themselves and parents (in which they learned how to make healthy snacks, for example); outdoor classes to promote physical activity and prevent sedentary lifestyles; and challenges to self-motivate to progressively reduce the time they usually spend in front of screens by consulting social media.
“In each institute, different adolescents have been chosen as leaders in this project and in the interventions that have been carried out (21 young people, among all the centers). We have called them ambassadors”, explain Judit Queral and Lucía Tarro, researchers of the project.
A key point that the teenage ambassadors of the SEEDS project decided to work on is promoting actions that help young people reduce the time they spend in front of screens. In this sense, different studies show, in recent years, that they are devoting more and more hours to consulting networks or playing video games, for example. The Digital report in 2020, from the Hootsuite platform and the We are social agency, shows that, on average, Spaniards (both teenagers and adults) spend 6 hours a day on the internet. On the other hand, the Interactive Advertising Bureau Spain finds that the generations called Z and Millennials (young people between 16 and 24 years old, and between 25 and 40, respectively) are the ones who are most attached to social networks. On average, they are present on 5.4 of these platforms, on which they spend an hour and twenty-one minutes a day.
“With the leadership of our own teenagers, boys and girls, we hope to contribute to increase the practice of physical activity and the consumption of healthy snacks by their peers while we build a better Europe”, concludes Rosa Solà, head researcher of the SEEDS project. Young people from high schools in Greece, the Netherlands and the United Kingdom also took part in the SEEDS project. More information and resources on the SEEDS project website: https://seedsmakeathons.com/
• The study will analyze the result of the interaction of aspects such as diet, environment or genetics, and its effects on children through metabolites, markers in blood and urine
• Data from more than 3,000 children of different ages and countries (in Spain these are patients of both the Hospital Universitari de Tarragona Joan XXIII and the Hospital Universitari Sant Joan de Reus) participating in this project will be collected on a web app. Thanks to its Artificial Intelligence based system, researchers and professionals in clinical practice will be able to interpret this information and make better decisions to improve patients’ treatments
A European study carried out by researchers from Institut d’Investigació Sanitària Pere Virgili (IISPV)-CERCA and Universitat Rovira i Virgili (URV) will reveal what happens inside our body when interacting key health-related aspects such as eating and sleeping habits, exercise, environment conditionings or genetics. All these aspects play a key role in the high incidence rates that obesity and its related diseases have currently in our societies (especially among the child population).
“The result of the interaction of diet, environment, schedules, genetics or exercise can be studied by analysing markers in blood and urine such as metabolites. Therefore, metabolites are molecules resulting from what it’s been used by our organism: from what we eat, consume… from what it’s eventually happening at the present moment inside us. By studying this we will be able to know how health-related habits, how everyone’s characteristics… interact with each other and, as a result, how they impact on us in a different way leading each person to either health or to illness”, explains Verònica Luque, a researcher in the Paediatric, Nutrition and Human Development Research Unit, which is part of the research group responsible for this study.
One of the most significant developments of this project in comparison to others that have been conducted in the same field is that it allows to collect a huge amount of data from children and adolescents from different ages and countries (3,300 people aging 0 to 18 participate in this study). In Spain these are patients of both the Hospital Universitari de Tarragona Joan XXIII and the Hospital Universitari Sant Joan de Reus.
Thanks to the application of Artificial Intelligence and bioinformatics (one of the centres which participates in this study has expertise in these fields), it will be possible to manage all these data in a way that allows and facilitates a more global understanding of the key aspects of growth and infant feeding.
The main biomarkers identified in this study will be collected in one web app with a view to applying them in the field of research and clinical practice, so that professionals can make better decisions to improve people’s health. “Once we have studied these metabolites in relation with diet and other health habits and we have obtained the results, we will design a web application with the help of bioinformatics. It could have potential applications in the clinic. For instance, at hospital, when monitoring obese patients, after analysing a specific metabolite in blood or in urine, we would introduce the values to this application and, in this way researchers or clinicians could obtain information on the patient’s diet, his or her metabolic state… In a research project we accumulate a huge amount of data; Artificial Intelligence helps us interpret them. We need tools that allow to transfer this knowledge to the reality of healthcare practice”, explains Verònica Luque. For all these reasons, this research group has been conceived from a multidisciplinary approach: dieticians, pediatricians, laboratory analysts and bioinformatics work together on a regular basis.
This study, entitled “Biomarker signatures of diet, physical activity and sleep in children and youth” has received funding from the Instituto de Salud Carlos III and the Next Generation EU, which supports the Recovery, Transformation and Resilience Plan (ref. AC21_2/00010) as well as from the European Union’s Horizon 2020 Research and Innovation programme under the ERA-NET Cofund action Nº 727565 (JPI HDHL).
The project has been preselected by the prestigious European research network The Joint Programming Initiative ‘A Healthy Diet for a Healthy Life’ (JPI HDHL), within the call for STAMIFY 2021 grants.
• The research group Nutrition and Metabolic Health-IIPSV-CERCA-URV is leading a study aiming to identify people at risk of developing this disease
• The results may allow to design targeted therapeutic strategies and to identify alterations produced across the progression of the disease
“Studies have found that 20 or 30 years before a diagnosis from Alzheimer’s disease (AD), metabolic alterations have already been identified in these patients”, states Mònica Bulló ( PhD), the principal investigator of the project and member of the research group of Nutrition and Metabolic Health of the Institut d’Investigació Sanitària Pere Virgili (IISPV) – Centres de Recerca de Catalunya (CERCA) – Universitat Rovira i Virgili (URV).
This research hypothesis is that alterations in the metabolism of the insulin appear before the AD has been diagnosed. This an important information considering that insulin resistance is frequent in people who are obese and in patients with type II diabetes. “As a matter of fact, both diabetes and obesity increase the risk of AD”, explains Bulló. This is the starting point for the international study that the Professor of the Department of Biochemistry and Biotechnology at the URV leads and promotes jointly with the researchers of the same group Christopher Papandreou and Jaume Folch. The aim of this project is to identify biomarkers for the diagnosis of AD in the early stages.
The study is carried out in collaboration with researchers of Alzheimer Center Barcelona and the Functional Neuroscience group of the Universitat Pablo de Olavide (Sevilla).
Previous metabolic alterations
Although Alzheimer was identified more than 100 years ago, an effective treatment has not yet been found. The finding of blood-based biomarkers for identifying people who are at risk of developing the disease would represent a very significant advance over the years: “In addition to better understanding the alterations that occur during the progression of the disease, targeted therapeutic strategies could be designed”, explains Bulló.
In addition to helping to prevent the disease in people at risk of developing it (with special attention to patients with type 2 diabetes and obesity), this approach would allow them to personalize their treatments and, therefore, advance in the field of personalized medicine, in which scientific debates are focusing their attention over the last years.
“So far, research into biomarkers has been at the level of cerebrospinal fluid. To get this type of samples implies some kind of risk and is not applicable as a screening tool”, explains Mònica Bulló. Thanks to Ace Alzheimer Center and the Universitat Pablo de Olavide will be possible to identify blood markers and relate them to brain markers as well as functional neuroimaging. “This gives us a tool more applicable to the population”, explains Bulló.
This project has been awarded with the Alzheimer’s Association Research Grant AARG-NTF-22-924702. It has started this month and will be running until 2025. Today, 800,000 people suffer from Alzheimer’s disease in Spain. It has been reported that the treatments for patients over 65 (in which the disease prevalence is highest) cost 10,000 million euros per year, which represents 1.5% of the gross domestic product (GDP).
