Team Director "Molecular and cellular pathophysiology of cardiometabolic diseases" within theUMR INSERM 1167 Rid-Age on the campus of thePasteur Institute of LilleDr. Jean-Sébastien Annicotte conducts research on cardiometabolic diseases, including the diabetes, the obesity and the Heart FailureHe seeks to understand how... environmental factorsFactors such as pollution and heat influence the development of these diseases. Therefore, he and his team are interested in... inter-organ communications, in particular those between the pancreas, adipose tissue and the heart.
Le Dr. Jean-Sébastien Annicotte leads the team CardioDiab "Molecular and cellular pathophysiology of cardiometabolic diseases" within the INSERM UMR 1167 Rid-Age. His work aims to understand how environmental factors can influence the development of diseases, particularly those affecting le coeur, the pancreas et adipose tissue such as obesity, diabetes et heart failure.
Can you tell us about your background and what led you to this research?
JS Annicotte: I am originally from the North and I studied the biochemistry in Lille, before completing my PhD in Strasbourg, in one of the most renowned molecular biology laboratories in Europe, theIGBMC (Institute of Genetics, Molecular and Cellular Biology), under the direction of Professor Johan Auwerx. That's where I started to become passionate about a question that may seem abstract but is actually fundamental: How do our genes regulate metabolism? How does a pancreatic cell decide to produce insulin? What causes it to malfunction in diabetes?
After my PhD, I spent several years in Montpellier, where I worked in particular on the links between cell cycle and metabolism a field at the crossroads of biology cancer and diabetes.
I returned to Lille in 2012, and gradually my research expanded. from the pancreas to the heart and adipose tissue, Because scientific questions naturally led me there. You can't understand diabetes without understanding what happens in the heart, and vice versa.
Today, I lead a team at the Pasteur Institute in Lille, and what motivates me remains the same as on day one: to understand the finest mechanisms of life in order to one day derive concrete benefits for patients.
What exactly does the term "cardiometabolic diseases" encompass? Why do these diseases represent a major public health and research challenge today?
JS Annicotte: Cardiometabolic diseases is a way of referring together diseases of the heart and blood vessels, as'infarct (Intergovernmental Panel on Climate Change) and the Stroke (Cerebrovascular Accident), and the metabolic disorders such as 2 type diabetes, the obesity or the dyslipidemiasthat is, abnormalities in blood fats.
They are grouped together because they share the same roots: a unbalanced diet, the inactivity, the excess abdominal fatand common biological mechanisms such aschronic inflammation or insulin resistanceIn other words, they mutually support each other and often have the same underlying causes.
When we look at the figures, cardiometabolic diseases are now the leading cause of death worldwideBut what really worries researchers is the trajectory. With sedentary lifestyles, ultra-processed foods, and aging populations, the number of people affected is exploding. It is estimated thatone in three adults in Western countries is in a high-risk situation. It is therefore a major public health issue.
Your work focuses in particular on what is called “inter-organ crosstalk”. How can this be defined simply and why is this approach important for a better understanding of cardiometabolic diseases?
JS Annicotte: This is a question that goes to the heart of what has long been a problem in biomedical research: for decades, we studied each organ in isolation: cardiologists focused on the heart, diabetologists on the pancreas, and so on. This is understandable, but it caused us to miss something essential.
Imagine that your organs don't work silently, each in their own corner, but thatThey communicate constantly. That is exactly what this term means. “crosstalk”, which could be translated as dialogue or inter-organ communication.
These messages take very concrete forms: hormones, small molecules, fragments of genetic information which circulate in the blood and modify the behavior of a distant organ. These exchanges are constant and bidirectional.
What is important to understand is that in cardiometabolic diseases, this dialogue is breaking downThe organs begin to send each other bad signals, and this is often This breakdown in communication precipitates the illness. sometimes well before symptoms appear.
Why is this so important for research? Because if we can precisely identify what these signals are, when they malfunction, and why, we can hope intervene very early in the chainNot just treating the consequences, such as heart attack or diagnosed diabetes, but interrupting the process upstream.
Your team is trying to understand how environmental factors can influence the functioning of our cells. What factors are we talking about exactly, and how can they contribute to the development of diseases such as diabetes, obesity, or heart failure?
JS Annicotte: When we talk about environmental factors in this context, we're talking about everything what our bodies are exposed to on a daily basis, And the list is longer than you might think.
There are, of course, the great classics: what we eat, whether we exercise or not, tobacco, alcoholBut there are also factors that are less often considered: the quality of sleep, the chronic stress, and especially the pollutants the endocrine disruptors These substances, found in certain plastics or pesticides, and in the fine particles we breathe in cities, have the ability to directly interfere with the functioning of our cells.
What's fascinating, and this is at the heart of what we're studying, is that these factors don't act by altering our DNA, our genetic code. They act on how our genes are expressedwhich are activated or put into standby mode. This is what is called...epigeneticAnd these changes can have very concrete consequences: they can disrupting the way our cells process sugar or fats, altering the function of heart cells, or triggering persistent inflammationThese are processes which, in the long term, promote the emergence of diabetes, obesity or Heart Failure.
JS Annicotte: What makes this field particularly important is that, unlike genes, which cannot be changed, These epigenetic modifications are potentially reversible. This is a real therapeutic avenue.
To study these interactions between organs, you are developing so-called multi-organ-on-chip models. Can you describe these multi-organ-on-chip models and explain what they allow you to study?
It's a rather remarkable technology, and still largely unknown to the general public. The basic idea is to To reproduce, on a very small scale, the functioning of several human organs, and especially their interactions, on a device about the size of a USB key.
In practical terms, we cultivate real human cells in tiny rooms connected by micro-channels in which circulates a fluid that plays the role of bloodThese cells live, function, and above all communicate with each other exactly as they would in an organism.
This is important for several reasons. First, we work with human cells, which makes our results more direct transposable to human physiologyNext, drugs or environmental exposures can be tested in conditions much closer to biological reality.
That said, we must be honest about the limitations: these models remain simplificationsWe are far from reproducing the complexity of an entire organism—the immune system, the vascular system, the hormonal interactions on a body-wide scale. These are tools. powerful, but complementary other models and clinical studies, not perfect substitutes.
You are collaborating with several European teams, notably in Rouen, on a project dedicated to heart failure. What do you hope to ultimately achieve for patients through this work?
JS Annicotte: This collaboration is part of a european project funded by the ANR (National Research Agency) which brings together four teams: ours in Lille, a team in Rouen led by Professor Paul Mulder who coordinates the project, a team in Maastricht in the Netherlands led by Dr. Miranda Nabeen, and a team in Krakow in Poland led by Professor Stefan Chlopicki.
The starting point is a very concrete and very serious clinical problem: decompensated acute heart failureThis is what happens when a heart failure patient's condition deteriorates suddenly and they need to be hospitalized urgently: severe shortness of breath, edema, intense fatigue. It's here leading cause of hospitalization among people over 65 in Europeand today it does not exist no treatment capable of preventing these relapse episodes.
In this context, the episodes of high heat play an important role. When it's very hot, the heart must work much harder to regulate body temperatureFor a healthy heart, it's manageable. For a heart already weakened by diabetes, hypertension, or heart failure, it can tip the patient towards a vital emergency.
What we are trying to do is Identify heart failure patients well in advance who will poorly tolerate a heat wave, even before the heat wave arrives. For this reason, we are working to identify circulating biomarkers These are molecules present in the blood that would indicate a patient is at particularly high risk. A simple blood test could then be enough to trigger enhanced monitoring or an adjustment of treatment before the summer.
The second contribution is therapeuticThe cellular mechanisms we highlight are potentially targets for new drugsAnd the advantage is that some of these medicines already exist and are being tested for other diseases. The path to patients could therefore be shorter than previously thought.
Finally, there is a broader public health issue: helping to define specific care protocols for heart failure patients during heat waves, that is to say concrete recommendations for healthcare teams.
The long-term objective is quite clear: to no longer be in reaction, but in anticipation.
In conclusion, what message would you like to convey to the general public about cardiometabolic diseases, their prevention, and the impact of climate change on health?
JS Annicotte: In the vast majority of cases, cardiometabolic diseases develop silentlyFor years, under the influence of well-known factors, the inactivity, the diet, the tobaccoand factors that we are only now beginning to measure better, such as the heat or Pollution.
The message I want to convey is that the Prevention remains the most effective strategy which we have available. And faced with Summers are becoming increasingly hot and deadly., this urgent need for prevention becomes even more critical for the most vulnerable patients.
What we are trying to do in the laboratory is lay the scientific foundations that could, in time, allow us to better anticipate and better protect These patients. The path between a fundamental discovery and a clinical application is always long and uncertain; that's the reality of research. But if we don't start asking the right questions today, we won't have the answers when we need them.
