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Art and Science program: Inserm at the Rencontres d’Arles and Avignon Festival

Sans titre, tirage 60x50cm ©Diane Hymans, 2019 La recherche de l’art #8

Inserm is reaching out to a new audience among the general public this summer by taking part in two events that bring together art and science in a mutually enriching way: the 8th Recherche de l’art (Art of Research) exhibition at the Rencontres d’Arles, in partnership with the École nationale supérieure de la photographie, and the 10th edition of the binôme program at the Avignon Festival, led by the Les sens des mots theater company.

Inserm is inviting the general public to come and discover a different side to medical research at two arts events in which it is taking part: La recherche de l’art #8 and the 10th edition of the binôme program.

These partnerships look at biomedical research through the lenses of photography and theater, transforming it into artistic material and offering a new vision of science that is accessible to all. To mark these summer events, spread over July and August some of the photographic work on display will also be showcased through the Inserm Instagram account.

 La recherche de l’art #8

Since 2011, a partnership between Inserm and the École nationale supérieure de la photographie d’Arles (ENSP) has brought medical research together with photography. Recent ENSP graduates complete a 3 to 4-week photographic residency in an Inserm laboratory, turning it into a center of photographic investigation in which art is used to discover science and present it in a different way. Their work will be shown at the Rencontres d’Arles, culminating in the exhibition La recherche de l’art #8 and in a publication.

For the eighth year of the program, Inserm welcomed 4 artists in residence: Hélène Bellenger (in Tours, Unit 1253 Imaging and Brain), Quentin Carrierre (in Dijon, Unit 1093 Cognition, Action and Sensorimotor Plasticity), Diane Hymans (in Nice, Unit 1091, Valrose Institute of Biology), and Pauline Rousseau (in Paris, Unit 970, Center for Cardiovascular Research at the Georges-Pompidou European Hospital). Their work will be exhibited from July 1 to August 25 in the new ENSP building.

Throughout the exhibition, the general public will also be able to discover some of the work via the Inserm Instagram account.

Art of Research #8 exhibition

July 1, 2019 to August 25, 2019

Free entry daily from 10 a.m. to 1 p.m. and from 2 p.m. to 7 p.m. at ENSP

Boulevard Victor Hugo 13 200 Arles

Opening event with the artists in attendance: July 2, 2019 at 5 p.m. Discover the work on the @Inserm Instagram account

 

For more information: https://www.ensp-arles.fr/inserm2019

 

 

binôme: 10th edition as part of the “In” program at the Avignon Festival

 

This year sees theater company Les sens des mots presenting its 10th series of binôme performances as part of the “In” program at the Avignon Festival. Inserm has partnered with binôme from the beginning, helping to develop new visions of science by bringing together the worlds of research and contemporary theater.

 

binôme consists of a series of performances developed from a meeting and discussion between a researcher and a dramatist. Each meeting results in a piece of theater that is loosely inspired by the encounter, in which the researcher and his or her work becomes the dramatist’s subject. The performance combines:

  • a screening of extracts from the filmed meeting between the dramatist and the scientist;
  • a reading of the play by members of the Les sens des mots theater company;
  • the filmed reaction of the scientist as he or she sees the play for the first time;
  • a public discussion with the dramatist, scientist, and artistic team.

This year, Inserm and binôme are inviting the general public to discover Élise louche!, a play by dramatist Hédi Tillette de Clermont-Tonnerre based on his meeting with Alain Chédotal, Inserm research director in developmental neurobiology at the Institut de la Vision (Inserm unit 968/CNRS/Sorbonne Université).

The first performance will be held in Avignon on July 15.

Monday July 15 – 5.30 p.m.: Élise louche! Avignon Université – Les Jardins de l’Université 74 rue Louis Pasteur

View the full program of binôme performances at the Avignon Festival and book tickets at: https://www.lessensdesmots.eu

Les sens des mots press contact: Valérie Mastrangelo

+33 (0)6 58 11 24 80

ue.stomsedsnessel@olegnartsam.eirelav

No rest for neurons during sleep

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An Inserm team has provided the first description of the behavior and language of the neurons responsible for memory consolidation during sleep. The researchers have shown that, far from being organized in a static and linear way as was previously thought, neurons vary in their role over time, and that information pathways are continually changing. Their research has been published in Science Advances.

Brain cells are continually exchanging information. During sleep, this plays a particularly important role in consolidating memory. But little is currently known about how these exchanges take place. Electroencephalograms, which measure overall electrical brain activity, show regular waves that vary in speed depending on the phase of sleep, but do not provide information about how information is processed at the neuronal level. This is what the team led by Christophe Bernard (Institute of Systems Neuroscience – Inserm U1106) have succeeded in revealing. To do so, the team used electrodes to record electrical activity from around a hundred neurons concentrated in a particular region. It is these electrical signals that carry information. Three areas known to be involved in memory were recorded in rats during sleep: the hippocampus, prefrontal cortex, and entorhinal cortex.

“Because of the regularity of waves seen on the encephalogram, we thought that neurons worked in a very precise and repetitive way to transmit or store information (rather like a fine-tuned machine). But the recordings show that this is not at all the case,” notes Christophe Bernard.

Groups of neurons organize themselves for very short periods to store and transmit information, and continually take turns over time. And within each group, only a few neurons play a dominant role. “So there’s a sequence of substates, with ultimately around half of the neurons in these three regions playing a key role in processing information from one moment to the next. In other words, there is no hierarchy among the neurons, but rather an even distribution of roles,” explains Christophe Bernard.

Free-flowing circulation

The other major discovery is that, during a given substate, the information does not always follow the same pathway. “This came as a surprise, as the dominant theory was that information transfer followed a set pathway. But we found that this is not the case. In the brain, the partners with which a neuron exchanges information fluctuate from one moment to the next. It works a bit like the internet,” illustrates the researcher.

“An email sent from Paris to Sydney passes through servers located in various countries during its journey, and these servers vary over the course of the day depending on traffic. It’s the same in the brain: even if the information is the same, it does not follow a set pathway, and the partners are never the same.”

Finally, this research has made it possible to decode the type of language spoken by the neurons. If a substate corresponds to a “word,” then the sequence of substates constitutes a sentence. But while the meaning of the words and sentences still evades the researchers, they have been able to establish that the neurons speak a complex language, which makes it possible to optimize information processing. A simple language contains very few words; it is easy to understand but struggles to convey complex concepts. A chaotic system of language contains a word for every possible situation, and is impossible to learn. The language of neurons is complex, like human languages, and its complexity is notably greater in paradoxical sleep (during dreams) than in deep sleep.

The researchers will now look at what happens during the waking state, when performing specific tasks, or in disease. This will include studying the possible link between memory loss in subjects with epilepsy and the complexity of neuronal language.

Acting on the immune system even before cancer develops may be feasible

Visualisation en coloration multispectrale d’une sous-population de cellules immunitaires infiltrant une tumeur. Inserm/Jerôme Galon

The immune response is activated from a very early stage in the development of precancerous cells. Unfortunately, this response is simultaneously accompanied by the onset of mechanisms that block it, allowing cancer to develop. This is the first time that the immune response has been described in such detail in precancerous stages, here in lung cancer. This research conducted by the team led by Jérôme Galon, Inserm research director at the centre de recherche des cordeliers (Inserm/Université de Paris/Sorbonne Université) in Paris, shows that using immunotherapies at very early stages could potentially help prevent cancer. This research has been published in Nature.

Our understanding of how the immune system works in the context of cancer is continually improving. Jérôme Galon and his Inserm team have made a significant contribution to such advances. After showing that cancer progression depends among other factors on the presence and functionality of T lymphocytes in the tumor microenvironment and the Immunoscore, the researchers have proven that the immune response and its blocking mechanisms are triggered at very early, precancerous stages.

This means that when a cancer develops, many components of immune surveillance but also the mechanisms designed to evade it have already been implemented.

At the moment, patients with precancerous lung lesions can be monitored and the lesions removed if doctors have the slightest suspicion that they are at risk of developing into cancer. But clinicians may be surprised to discover that it may already be possible at this stage to target the immune system in order to combat progression of these lesions. This is what the research by Jérôme Galon and his team has shown. The researchers had access to 122 lung biopsies from smokers at risk of cancer. They found all stages of precancerous to cancerous lesions in these biopsies. For each biopsy, they studied the immune system in the tumor microenvironment. They performed a genomic analysis of the cells present and looked at them using multispectral fluorescence, an imaging technique that uses specific antibodies to target different types of immune cell. This work enabled them to characterize the nature, quantity, and role of the various immune components in the tumor microenvironment at each precancerous and cancerous stage.

The immune response takes place before cancer

This made it possible for them to compare the development pathways of the cancer and the immune response. At the stage of low-grade dysplasia – an extremely early stage, when only a few morphological abnormalities, DNA repair defects, and greater ability to divide can be seen in the cells – the researchers observed activation of local immune cells and the arrival of naive T lymphocytes, i.e. T cells not trained to specifically destroy abnormal cells. At the stage of high-grade

dysplasia – where there is a higher level of morphological and molecular abnormalities – the researchers then observed mass recruitment of innate and adaptive immune cells, with the presence of B and T lymphocytes specific to abnormal cells and initiation of the immune memory response. But such activation is already accompanied at this stage by the triggering of blocking mechanisms called immune checkpoints and of immune suppressive cytokines, molecules that are also designed to block the immune response. This means that the functioning of the immune system is already altered before the cancer itself develops. This discovery in the context of lung cancer still requires confirmation in other types of cancer. Jérôme Galon is already working on doing so in colon cancer.

The researchers believe that this work will have major implications for the future of patient care. First, they highlight the importance of discovering immune biomarkers that will make it possible to better predict the risk of precancerous lesions developing into cancer.

Second, using immunotherapies designed to inhibit the mechanisms that block the immune system, the much talked about immune checkpoints, could be of benefit to patients in the early stages of cancer prevention.

A New Therapeutic Target for Treating Spinocerebellar Ataxias?

Cellules de Purkinje dans une coupe horizontale du cervelet de souris exprimant une protéine fluorescente (GFP) sous le contrôle du promoteur des récepteurs dopaminergiques D2. Ces cellules dégénèrent chez les patients atteints d’ataxie spinocérébelleuse SCA3. ©Inserm/Valjent, Emmanuel

Spinocerebellar ataxias are neurodegenerative genetic diseases of the cerebellum and brain stem that lead to numerous motor disorders. The most well-known of these ataxias is SCA3, which is also called Machado-Joseph disease. In her research published on June 14 in Acta Neuropathologica, Nathalie Cartier-Lacave, Inserm researcher at the Brain and Spine Institute, discovered with her team the crucial role of an enzyme that can improve symptoms of this disease in mice.

Certain neurodegenerative diseases are caused by a mutation that leads to the production of malformed proteins in possession of excess amino acids (polyglutamine expansion). This occurs with Huntington’s disease and some forms of spinocerebellar ataxia.

In this study, a team from the Brain and Spine Institute (Inserm/Sorbonne Université/APHP) led by Nathalie Cartier-Lacave looked at another group of diseases that presents this polyglutamine-expanded protein production – spinocerebellar ataxias – and more specifically SCA3. In this disease which affects 1-2 in every 100,000 people, the ataxin 3 protein mutates and aggregates in neurons, leading to their death and the subsequent onset of motor disorders. The researchers were able to show that supplying a key enzyme of brain cholesterol metabolism, CYP46A1, to the regions affected by the disease improves symptoms. A strategy that could also be effective in the other ataxias linked to polyglutamine expansion.

The researchers began by studying the cholesterol metabolism in mice with SCA3, revealing an imbalance in this metabolism and decreased levels of the enzyme CYP46A1.
These initial findings led the researchers to test whether or not restoring the expression of this enzyme in SCA3 mice could be beneficial. They performed a single injection of a gene therapy vector carrying gene CYP46A1 into the cerebellum of SCA3 mice, revealing reduced degeneration of the Purkinje neurons of the cerebellum, an improvement in the motor disorders, and decreased ataxin 3 aggregates when compared with untreated mice with the disease.

“These findings show that CYP46A1 is an important therapeutic target for restoring this metabolism, decreasing
toxic mutated protein aggregates and thereby improving the symptoms of the disease”, explains Inserm Research Director Cartier-Lacave.

To further elucidate the phenomenon, the researchers revealed that the pathway used to evacuate the malformed or mutated proteins – the autophagy pathway – is disrupted in SCA3 mice. This led them to conclude that ataxin 3 proteins aggregate as a result of dysfunction of this pathway. However, if normal CYP46A1 levels are reinstated, autophagy is restored, and the disease symptoms attenuated.

Interestingly, the researchers also observed improved evacuation of the ataxin 2 aggregates during overexpression of the enzyme, leading to hopes for treatment, with one product having the potential to be effective in multiple severe and rare diseases.

A European program (Erare) coordinated by Inserm at the Brain and Spine Institute (N. Cartier, A. Durr) is in progress to confirm these results on other models of ataxia and to evaluate the feasibility and tolerance of a potential therapeutic application in patients with these severe genetic diseases.

When Moss Reflects Air Pollution

©Photo by Michaela on Unsplash

Despite the increasing research into and recognition of the role of particulate matter in the excess mortality caused by air pollution, it is still poorly understood. A research team from Inserm and Université Versailles Saint-Quentin-en-Yvelines used an innovative method based on the biomonitoring of metal levels in mosses in rural France. Over 15 years, the team mapped levels of metals − including lead and cadmium − in mosses. The results were then compared with mortality data from the Gazel cohort. Their findings, published in Environment International, point to a link between long-term exposure to atmospheric metals and excess mortality, even in areas remote from major sources of emissions. They confirm the utility of moss biomonitoring as a tool to evaluate the effects of exposure to air pollution.

External air pollution has been recognized as being responsible for 4.2 million premature deaths in 2016, and scientific evidence continues to accumulate in regard to the role played by particulate matter. Produced by both human activity and natural sources, particulate matter contains various metals. Its role in morbidity and mortality however is poorly understood, with little research into the health effects of exposure to atmospheric metals. Often limited by the absence of widespread monitoring stations, studies focus on areas of high exposure or population density (cities, proximity of major roads or polluting industries).

Biomonitoring metal levels in moss [1] is an approach which, although it does not measure them directly, is able to evaluate over time the level and variations of atmospheric concentrations of heavy metals deposited on mosses.

A research team from Inserm and Université Versailles St-Quentin-en-Yvelines compared moss biomonitoring data in France with epidemiological data from the Gazel cohort in order to deepen its understanding of the effects on mortality of long-term exposure to atmospheric metals in areas with low levels of exposure to human emissions.

Over 15 years – from 1996 to 2011 – the researchers mapped levels of 13 atmospheric metals (aluminum, arsenic, calcium, cadmium, chrome, copper, iron, mercury, sodium, nickel, lead, vanadium and zinc) in mosses using readings taken as part of the French National Museum of Natural History moss biomonitoring program. They distinguished between metals of natural origin and those of anthropogenic origin (human activity) – the latter being lead, cadmium, copper, mercury and zinc. The health data of over 11,000 Gazel cohort participants living in rural and suburban areas were compared with this mapping.

The researchers observed an increased risk of death from natural causes for the simultaneous exposure to all of the anthropogenic metals. Exposure at shorter distances from major roads appears linked to a higher mortality increase than exposure at longer distances, which could indicate a link between exposure to atmospheric metals produced by road traffic and mortality.

Some atmospheric metals produced by human activities could therefore be linked to excess mortality even in the areas where exposure to air pollution is low. ” Previous studies within the Gazel cohort had shown that those living in urban areas were a lot more exposed to particulate matter than those living rurally and so had a high likelihood of exposure to atmospheric metals, states Bénédicte Jacquemin, the Inserm researcher having led the study. City-dwellers are therefore probably more subject to the health effects of atmospheric metals. “

And to conclude: The results of this study confirm the utility and relevance of moss biomonitoring as a tool to evaluate the effects of exposure to air pollution. Further studies are needed in order to specify which of the metals contained in the particulate matter are likely to affect human health, which would give us a deeper understanding of the effects of atmospheric pollution on health. 

[1] In France, the BRAMM program, managed by the French National Museum of Natural History, uses moss biomonitoring for many atmospheric metals, with the objective of monitoring levels of these metals mainly in forests and areas remote from major industrial, urban and traffic sources. This monitoring involves sampling mosses at sites across France, recording the location of each collection site and analyzing their metal content in the laboratory.

Inserm Research Director Jérôme Galon Wins European Inventor Award 2019

Inserm: Science for Health

Jérôme Galon©Inserm/Mehrak

Inserm researcher Jérôme Galon has been honored by the European Patent Office (EPO) for his Immunoscore®, a test that predicts relapse risk in patients with certain forms of cancer. An achievement that encapsulates the missions and results of Inserm, a research institute serving good health for all.

The invention of Jérôme Galon – under license from the French National Institute of Health and Medical Research through its private subsidiary Inserm Transfert and marketed under the name Immunoscore® by the company he co-founded – is used to count the immune cells in patient tumor tissue. The more these immune cells are present in the tumor, the better the patient’s chances of survival. In colorectal cancer, the test has a 95% likelihood of predicting patient survival. Immunoscore® gives doctors a more complete picture of the disease, enabling them to offer the most appropriate treatments to their patients.

To perform the test, a specialized scanner produces digital images of tumor samples, from which software will count the number of immune cells. An algorithm then calculates the patient’s Immunoscore® based on the number of T-cells. Clinics throughout the world now use this test to predict relapse risk in patients with colorectal cancer.

“Jérôme Galon’s journey is exemplary in many respects and I offer him my warmest congratulations on winning the European Inventor Award 2019. Through Jérôme, it is the results of our research that are rewarded – when this research succeeds in bringing science and enterprise together. It is also a fine example of our motto at Inserm: Science for health”, declares Inserm Chairman and Chief Executive Officer, Gilles Bloch.

“With 165,000 patent applications filed in Europe every year, I am delighted to receive this award honoring more than 15 years of laboratory work – work that is still ongoing. It is also thanks to the freedom of research afforded to us at Inserm that I was able to embark on this research, over the long term, back when few researchers were interested in cancer immunology. In terms of creating value from this discovery, Inserm Transfert has also played a decisive role by supporting me throughout my journey”, states Galon.

Human Adipose Tissue Reproduced in the Lab

©STROMALab

Can human adipose tissue be reproduced in a laboratory? It can now, thanks to a research team with members from Inserm, CNRS, Université Toulouse III-Paul-Sabatier, the French Blood Establishment (EFS) and the National Veterinary School of Toulouse (ENVT) working together at STROMALab. This team used 3D culture to develop adipose tissue organoids (or adipospheres) – small cellular units that mimic the characteristics and organization of adipose tissue as it presents in vivo. In their article, published in Scientific Reports, the researchers describe the various stages of the experimental conditions needed to obtain these adipospheres from human cells. An innovation that could make it possible not just to study diseases related to the impaired functioning of this tissue, such as obesity and type 2 diabetes, but also to develop new drugs to treat them.

Human adipose tissue, highly vascularized by a network of capillaries, is made up of fat cells known as adipocytes. Until now, laboratory researchers used 2D models that did not take into account the 3D architecture of this tissue as found in the human body.

Mini organs, which are known as organoids and capable of reproducing the cellular organization of a specific organ, have already been developed for some tissues, such as that of the intestine. However, none had been able to reproduce in 3D the cellular and vascular organization of the adipose tissue in a laboratory setting.

However, this is now possible thanks to researchers from Inserm, CNRS, Université Toulouse III-Paul-Sabatier, the French Blood Establishment (EFS) and the National Veterinary School of Toulouse (ENVT) working together at STROMALab. Thanks to the advent of the new 3D cell culture methods, the control of the selection and characterization of adipose tissue stromal cells (support cells), the team was able to develop organoids of this tissue, called adipospheres.

Generating organoids in 3D

From these stromal cells of the human adipose tissue, the researchers developed new 2D – followed by 3D – culture conditions, making it possible to obtain both adipocytes and endothelial cells from this tissue. The adipospheres obtained contained an intact vascular network organized around adipocytes in the same way as in actual human tissue. Better still, the adipocytes obtained were capable of differentiating into those of brown or white tissue (the two types of human adipose tissue) in the same way as those encountered in the human body.

Transplantation in mice

The research team then transplanted these adipospheres into mice in order to verify the functionality of their vascular network. They observed that not only was this network maintained in the body but also that it extended itself by establishing connections with the host’s circulatory system.

The researchers also observed so-called chimeric vessels, constituted of both mouse and human cells. “These are all signs that the host tolerates the transplanted organoids well, explain Isabelle Ader, Inserm researcher, and Frédéric Deschaseaux, from the French Blood Establishment (EFS), authors of the study. From this we can conclude that not only are these small structures faithful to the organization of human tissue, but also that they are capable of staying alive by establishing connections with the host circulatory system that provides them with the necessary oxygen and nutrients.

According to the researchers, this innovation will enable continued study of the functioning and properties of human adipose tissue. By working directly on this tissue, the use of animals will be reduced.

This innovation will also make it possible to test various drugs that could be used to treat certain diseases related to a pathology of adipose tissue, such as obesity or type 2 diabetes“, conclude Isabelle Ader and Frédéric Deschaseaux.

Read the article (in french) published in Magazine de l’Inserm, n°43, Juin 2019.

Better air quality: what should the target values be for improving health?

©Photo by Pierre Herman on Unsplash

To produce a significant reduction in mortality due to fine particulates, their average level should be reduced by at least 3 micrograms per m3 as a yearly average, concludes an interdisciplinary study led by researchers from Inserm, the CNRS, INRA, Atmo Auvergne Rhône-Alpes and the Université Grenoble Alpes. This work, published in Environment International, also provides an estimate of the costs of pollution in urban areas: €1200 per inhabitant per year in the Lyon and Grenoble conurbations.

Exposure to fine particulate matter (PM2.5) is recognized to have significant effects on health in urban areas (including cardiovascular and respiratory mortality and disease, and pregnancy and fetal growth problems), but can be reduced. However, public policies designed to reduce atmospheric pollution are often developed without setting the explicit health benefits to be achieved.

So what should the target values be if we want to significantly improve health, decrease health costs, and reduce environmental inequalities? A multidisciplinary team of researchers (epidemiologists from Inserm, biologists and economists from the CNRS and INRA, and air quality specialists from Atmo Auvergne Rhône-Alpes) looked at different hypothetical scenarios for improving air quality in order to identify those that would be most effective.

First, yearly average exposure to PM2.5 was estimated using air quality observation tools and data on the location of housing in the Grenoble and Lyon conurbations (0.4 and 1.4 million inhabitants respectively). Based on previously established dose-response relations, the researchers estimated variations in the number of deaths and cases of lung disease, life expectancy, and associated economic costs for ten different scenarios for reducing PM2.5.

Using the actual situation over the period 2015-2017 as a baseline, with an average concentration of around 14 and 15 µg/m3 in Grenoble and Lyon, and comparing it to a hypothetical situation without human-produced fine particulates (equating to a concentration of 4.9 µg/m3), fine particulate pollution was considered to be responsible for 145 deaths per year in Grenoble (5.6% of deaths, with a 2% margin of error either way) and 16 cases of lung cancer. In Lyon, the respective numbers were 531 and 65. The associated costs, which included tangible costs linked to treatment, but also “intangible” costs linked to the psychological impact on friends and family, came to nearly 500 million euros per year in Grenoble and 1.8 billion/year in Lyon.

10 scenarios tested

The scenarios designed to obtain spatially homogeneous exposure to pollution across the entire study area were the most effective. “Measures that are highly spatially limited – or limited by time, for example, to ‘peak’ pollution periods – would appear to have a much lower impact on both mortality and on reducing health inequalities, ” explains Rémy Slama, Inserm research director.

In relation to mortality, reducing exposure to PM2.5 in line with the WHO (World Health Organization) guideline value for air quality (10 μg/m3) would halve mortality attributable to PM2.5 of human origin, while a reduction of 2.9 μg/m3 (Grenoble) and 3.3 μg/m3 (Lyon) would be required to reduce the mortality attributable to these particulates by a third. It is not simply deaths among vulnerable individuals that would be prevented: life expectancy would also simultaneously increase by around 3 months.

This kind of study can be easily transposed to other conurbations, and may help French cities, many of which have similar levels of pollution to those in Grenoble and Lyon, to focus on scenarios for reducing atmospheric pollution that make it possible to significantly improve health and well-being. The team of researchers is now working to identify the concrete measures that might be taken in relation to the main sources of pollution (heating and road traffic) in order to achieve such a decrease in pollution concentrations.

This study was carried out as part of the QAMECS and MobilAir projects supported by ADEME, Grenoble-Alpes Métropole and IDEX Université Grenoble Alpes.

The natural lipids in buttermilk could contribute to reducing cardiovascular risk in vulnerable populations

A French consortium led by INRA, in collaboration with INSERM, the Universities of Lyon and Clermont Auvergne, Lyon Civil Hospitals and the Human Nutrition Research Centres (CRNH) of Rhône-Alpes and Auvergne, have now demonstrated that consuming certain lipids present naturally in dairy products (called “polar lipids”) could reduce the cardiovascular risk in overweight postmenopausal women by lowering their blood levels of LDL-cholesterol (“bad” cholesterol) and triglycerides. To reach this conclusion, the scientists included a cream cheese enriched in buttermilk polar lipids in the daily diet of volunteers for a period of one month. They were able to reveal certain mechanisms in the gut that might explain the effects observed. These natural dietary compounds could therefore form part of a new nutritional strategy designed to reduce the cardiovascular risk in vulnerable populations. This work was published on 12 June in Gut.

Dairy products contain a wide variety of lipids, both triglycerides and polar lipids, the latter being specific lipids that naturally stabilise fat droplets and are notably found in cream and buttermilk. Polar lipids play a crucial physiological role as they are essential components of cell membranes. Preliminary experiments in rodents had revealed the beneficial effects of milk polar lipids on liver metabolism and the regulation of blood cholesterol levels. However, until now, these effects had never been demonstrated in human volunteers with a high cardiovascular risk.

The research teams therefore tried to decipher the impacts of milk polar lipids on the cardiovascular risk profile of overweight postmenopausal women, a population that is particularly vulnerable to this risk. To achieve this, 58 such volunteers were asked to include cream cheese that was more or less enriched in milk polar lipids as part of their daily diet. After a month of consuming a specially-designed buttermilk concentrate enriched in milk polar lipids (a by-product of butter manufacture), the team observed a significant reduction in their blood levels of LDL cholesterol, triglycerides and other important markers of cardiometabolic risk. These milk polar lipids thus improved the cardiovascular health profile of these postmenopausal women.

The scientists then sought to unravel the mechanism underlying this effect. Their complementary studies suggested that certain milk polar lipids and cholesterol (of both dietary and endogenous origin) may form a complex in the small intestine that cannot be absorbed by the gut and is ultimately excreted in the stools.

These findings could ultimately provide foundations for new nutritional strategies to reduce cardiovascular risk factors in certain vulnerable populations.

Furthermore, they should contribute to a diversification of the ingredients used by the agrifood industry. Indeed, the functional properties of milk polar lipids relative to the texture of foods, alongside their potential protective effects on health, could offer a promising alternative to the soy lecithin that is currently used in a large number of foods, as well as providing an opportunity for the valorisation of buttermilk.

This work was carried out in the context of the ANR VALOBAB project (2012-2016) coordinated by Marie-Caroline Michalski, INRA Research Director in the Université Lyon 1-INRA-INSERM-INSA de Lyon Joint Research Unit for Cardiovascular, Metabolism, Diabetes and Nutrition (CarMeN). The project also involved the French Dairy Interbranch Organisation (CNIEL) and six other research laboratories and centres: CarMeN in Lyon, CRNH Rhône-Alpes, the Joint Research Unit for Human Nutrition and the INRA-UCA Joint Research Unit for Microbiology, the Digestive Environment and Health, both in Clermont-Ferrand, CRNH Auvergne, the INRA-AgroCampus Ouest Joint Research Unit for the Science and Technology of Milk and Eggs in Rennes, ENILIA (Surgères, with the participation of ACTALIA Produits Laitiers and Philolao) and ITERG (Bordeaux). The VALOBAB project received support from the ANR (ANR-11-ALID-007) and was accredited by the VALORIAL (Tomorrow’s Foods) Competiveness Cluster.

This clinical study, sponsored by Lyon Civil Hospitals, was also funded by PHRC-I VALOBAB.

Une étude montre des effets bénéfiques particulièrement importants du café dans le traitement d’une maladie neurologique orpheline

 

 

 

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