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24, chemin de Borde Rouge -Auzeville - CS52627 31326 Castanet Tolosan cedex - France

Last update: May 2021

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Human Nutrition Unit

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Email : contact
Tel : +33(0)4 73 62 47 32

  Research Activities       Publications       Curriculum vitae

Demographic changes in our countries are characterized by a progressive ageing of the populations. One of the major features of ageing is sarcopenia consisting in an unintentional and physiological loss of muscle mass and strength. Sarcopenia targets all ageing individuals, including persons presenting a good health status but prevails in frail population. It is a one of the major factor leading to incapacity and morbidity in the aged population. Sarcopenia is a physiological impairment due to various causes: malnutrition, lower physical activity, low grade inflammation, oxidative stress, obesity and gradual installation of an insulin-resistant state (IR).

My research program consists in the understanding of the early events leading to the installation of metabolic perturbations and the IR state both in healthy individuals fed an obesogenic diet but also in the elderly population. I focus my research on adaptive mechanisms developed by the body during IR installation and the impact of these mechanisms on nutrients (energy, nitrogen …) metabolism in insulin or nutrients-targeted tissues and organs (i.e. liver, gut and in fine muscle/adipose). More recent developments of my research area include the role of the gut microbiota in the development of IR and ageing-related metabolic perturbation, its interaction with the diet components and the synthesis of key metabolites (such as short chain fatty acids and other metabolites investigated by “omics” strategies) involved in the dialog between the host and its microbiota in these pre-pathological situations.Nutritional strategies, targeting gut microbiota, and capable to limit or delay the development of IR and age-related metabolic perturbations are also studied, particularly the role of dietary fermentable fibers and probiotics.

Activités de recherche

 Research Activities       Publications       Curriculum vitae

Integrative approaches are used and allow the investigation of interactions between tissues and organs for metabolisms regulation and nutrients bioavailability (gut/microbiota/liver/muscle, specific requirements and metabolisms or specific organs). We also investigate the impact of dietary components (proteins/energy substrates/dietary fibers/probiotics) on metabolic regulations at whole body and tissue level both qualitatively and quantitatively (bioavailability, net nutrients fluxes at tissue level, signals…)

These concepts are tested in human volunteers, rodents (including old rats), and an original model of mini-pigs multicatheterized at the digestive/hepatic or muscle levels. These different models allow an integrative and dynamic approach of metabolic fluxes of nutrients both at the whole body and tissue/cellular levels using labeled molecules, classical biochemical approach, metabolomics (plasma, urine, fecal water) and proteomics (at hepatic and muscle levels).

Key results:

Time events concurring to IR development in mini pigs : Ageing is characterized by a lower muscle response to the meal anabolic signal (particularly leucine). To this muscle-targeted mechanisms can be also associated alterations of metabolic cross-talks between tissues from the splanchnic area (gut and liver, including microbiota within the gut) and muscle for nutrients use. In a model of gut and liver catheterized mini-pig, we have shown that metabolic adaptations were occurring very early following the ingestion of an obesogenic diet (within the first 15 days) and that the liver and gut were adapting very quickly their energy metabolism to deal with the dietary overflow of nutrients (decreased glucose net uptake, increased lactate net production, rapid alteration of catabolism of branched chain amino acids).

Prebiotics : fermentable fibers. We have performed an integrated and comprehensive study of the interaction diet/microbiota/gut/produced metabolites from microbiota (from dietary fibers fermentation) or dietary origin on the bioavailability of nutrients to the peripheral tissues such as muscle (and kinetics of IR development). We have shown that a mix of fermentable dietary fiber was capable to reverse some of the adverse effects of a 2 months adaptation to an obesogenic diet in mini pigs: limitation of lipids droplets accumulation in the liver (via a decreased lipogenic activity and lipids entry in the hepatocytes) and increased oxidative capacity and mitochondrial activity in the muscle to catabolize the excess of lipids present in the diet. These latter data were obtained combining multicatheterized minipigs, “classical” biochemistry and molecular biology as well as “omics” methodologies: proteomics, metabolomics in the host and metagenomics of gut microbiota.

Probiotics : impact on the gut to target the muscle. We have shown, in old rats subjected to gut inflammation (induced by Sodium Dextran Sulfate, DSS), that a probiotic strain (Streptococcus Thermophilus) was capable to limit the DSS induced-hypermetabolism (and stimulation of protein synthesis) in the gut. This led to an increased availability of amino acids at the muscle level, a sustained protein synthesis and lower muscle loss in DSS-probiotic supplemented animals compared to DSS alone. The strain has been patented and underlying mechanisms of action under investigation.

Dr Isabelle SAVARY-AUZELOUX Publications

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