Accelerated Aging of the Cells of Visceral Adipose Tissue in Morbid Obese Subjects
Condition: Morbid Obesity
MeSH terms: Obesity; Obesity, Morbid
Study type: Observational

Summary: 
      Numerous epidemiological studies clearly showed the relationship between the excessive growth
      of visceral adipose tissue and risk of developing insulin resistance, type 2 diabetes and
      other cardiovascular risk factors. However, the mechanisms contributing to the deleterious
      role of visceral adipose tissue remain to be elucidated. Several observations suggest that
      adipose tissue depots exhibit distinct metabolic and secretory capacities according to their
      locations. We have recently shown that visceral fat depots display higher immuno-inflammatory
      cells infiltration than that of subcutaneous fat. In addition, the endothelial cells of
      visceral compared to subcutaneous adipose tissues express a pro-inflammatory phenotype and
      several markers related to aging. Finally, we have shown that visceral adipocyte-derived
      secretions promote the endothelial cell senescence in an extent higher than subcutaneous
      adipocyte-derived products. These data suggest that senescence 1) might be a phenomenon
      related to the location and therefore the microenvironment of adipose tissue and 2) might be
      responsible for an abnormal activation of proinflammatory response, favouring the development
      of metabolic and secretory dysfunction of adipose tissue in obesity. Our working hypothesis,
      based on these observations, is that the visceral adipose tissue provides a microenvironment
      that promotes accelerated aging. This senescence may be responsible for the establishment of
      an inflammatory reaction, alteration of the metabolic activity and adipocyte differentiation
      capacity of progenitor cells leading to the development of obesity associated diseases.

      The proposed project is a descriptive cross-sectional pathophysiological study .The aims are
      1) to better define the process of senescence in human adipose tissue, 2) to precise the
      mechanisms and 3) to analyse the cellular and functional consequences of aging on
      inflammation, adipose tissue development and metabolism. 200 morbidly obese candidates for
      bariatric surgery will be studied. The collection of clinical and laboratory data and the
      collection of biological samples (plasma, blood cells and subcutaneous and visceral adipose
      tissues) will be made at the inclusion and during surgery (obesity center, Hôpital Louis
      Mourier). Analyses of adipose tissue will be performed at INSERM U1048 and will focus on in
      vitro approaches of the cells of the adipose tissues (mature adipocytes, endothelial cells,
      progenitor cells and immuno-inflammatory cells).

      This project will permit to better understand the pathogenicity associated with the excessive
      growth of visceral adipose tissue and may reveal new therapeutic targets to limit
      obesity-associated pathologies.
    

Detailed description: 
      Main objective: The main objectives are 1) to compare the state of senescence of subcutaneous
      versus visceral adipose tissues and 2) to define the senescent cell populations in
      subcutaneous and visceral adipose tissues in morbidly obese patients.

      Secondary objectives: Secondary objectives are 1) to precise whether the state of senescence
      is attributable to microenvironment, 2) to determine the impact of aging on cellular
      function, 3) to establish a link between the state of senescence of subcutaneous and visceral
      adipose tissues and obesity-associated pathologies.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        hospital center
      
Biospecimen description: 
      adipose tissue
    
Keywords: obesity; adipose tissue; angiogenesis; senecence