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Last update: May 2021

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Human Nutrition Unit

Zone de texte éditable et éditée et rééditée

To prevent and predict

From the identification of muscle loss biomarkers and protein malnutrition to interventional strategies to preserve organ function



Identify biomarkers of muscle atrophy in humans
Muscle loss is an aggravating factor of several pathologies. However, no predictive tool exists for its early detection while it is almost impossible to revert muscle atrophy when it is established.
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Our goal is to identify biomarkers witnessing the development of muscle atrophy independently of the pathology. As a first step, we have identified 238 markers in skeletal muscles that are specifically over or under expressed during lung cancer or chronic kidney disease.

Our current studies focus on the identification of blood markers highly linked to the development of muscle atrophy. Our final goal is the development of a tool dedicated to routine detection of a catabolic situation in hospitals and/or to the follow-up of anabolic treatments.

To provide an integrative view of muscle aging in human, we combine proteomics, transcriptomics, immunohistology and molecular imaging to study sub-cohorts of elderly subjects without/with age-related pathologies. Using these methodologies, we identified potential biomarkers of muscle aging, and describe age/pathologies-related alterations in muscle fiber metabolism, lipid droplets, apoptosis, capillarization, satellite cells and fibrosis.

Investigators
Julien Aniort, Daniel Béchet, Agnès Claustre, Cécile Coudy-Gandilhon, Anne-Elisabeth Heng, Cécile Polge, Daniel Taillandier




Identification of predictive epigenetic marks of predisposition to the development of obesity
Context
Metabolic diseases (obesity, diabetes, etc.) are rising to dramatic proportions worldwide, making them a major public health issue. These pathologies are largely due to environmental causes, among which disorders associated with our lifestyle play an important role (diet, sedentary lifestyle, stress, etc.).
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However, all individuals are not equal when faced with environmental stresses and an individual's predisposition to the development of obesity results from interactions between one' s intrinsic predisposition and the environment. While genetic factors seem to play only a limited role, numerous epidemiological studies report that nutrition during the perinatal period is an important determinant of the individual's health status throughout life. These observations have led to the concept of Developmental Origins of Health and Disease (DOHaD). Thus, it has been shown (mainly by Barker et al.) that a maternal nutritional stress can result in specific adaptations in the fetus leading to an impairment of its physiology and metabolism and an increased predisposition to metabolic diseases in adulthood.
Identification of early predictive markers of obesity predisposition
Experimental models in rodents have shown that the imprints of the maternal environment can be epigenetic. The term epigenetics describes stable alterations in gene expression that do not involve any change in the DNA sequence. Epigenome development takes place during development, is strongly influenced by the environment, and is maintained through mitosis. The main epigenetic processes involved in the regulation of gene expression are the DNA methylation , post-translational modifications of histones and deregulated expression of small non-coding RNAs (in particular microRNAs: miRNAs).
We hypothesize that epigenetic imprints, occurring very early in development, can be considered as early predictive markers of susceptibility to the development of metabolic diseases.
Thus, we set up experimental nutritional models in mice, resulting in opposite obesity predisposition phenotypes (sensitive vs. resistant to the development of obesity). From these models, our project consists in identifying predictive epigenetic markers (DNA methylation and miRNA) specifically correlated to the observed metabolic phenotypes and having a predictive value, i.e. detectable before the appearance of clinical signs.
On the long term, our objective is to evaluate in humans all the previously identified epigenetic marks so that we can draw up a predictive test of predisposition to obesity to propose, before any clinical signs and any alteration of physiological indicators, a preventive treatment.

References

Investigators
Pierre Fafournoux, Céline Jousse, Laurent Parry