Lipophilic Organic Polluants and Morbid Obesity
Condition: Obesity
MeSH terms: Obesity; Obesity, Morbid
Study type: Interventional

Summary: 
      1. To study the kinetics of release after bariatric surgery of selected polluants stored in
           adipose tissue, looking for clinical and/or predictive factors

        2. To test the hypothesis of a deleterious effect of this release on the expected
           improvement of insulin-resistance and on the liver inflammation.

        3. To determine the level of contamination of morbidly obese patients, with or without
           metabolic syndrome, compared to a control, non obese population, with special attention
           to clinical (age, gender, reproductive history, pregnancy, nursing) and biological
           parameters (insulin-resistance, inflammation).
    

Detailed description: 
      I- Goals Because of its exponential prevalence and its co-morbidities, obesity, particularly
      in its most massive forms, has become a public health problem. It is likely that this
      epidemic be secondary to both genetic and behavioural factors, and also to environmental
      factors. Specifically, the "obesogen" and "diabetogen" role of several persistant organic
      polluants (POP) known as endocrine disruptors used in farming or industry has recently been
      suggested by experimental animal studies and by human epidemiologic studies. Those chemicals
      are usually lipophilic, are stored in adipose tissue where they bio-accumulate, and are
      released in the blood stream during the lipolysis that occurs in any weight loss. This weight
      loss is particularly rapid and important after bariatric surgery, that is proposed as a
      treatment for morbid obesity usually leading to an improvement of insulin resistance,
      metabolic syndrome, and diabetes. However, this improvement is not constant, or is less
      important than would be anticipated for the massive weight loss observed. This raises the
      question of the importance and of deleterious impact of the blood release of lipophilic POPs
      on the evolution of metabolic syndrome and the low grade associated inflammation.

      In a prospective, multicentric study, we propose to analyse the kinetic of the release of
      several POPs during rapid and massive weight loss obtained after bariatric surgery. Those
      POPs have been chosen for their obesogen or diabetogen properties, reported in vitro or in
      vivo, for their lipophilic nature, and their ubiquitous presence in the home environment
      and/or into the food chain: bisphenol A (plastics); tributyltin (fungicide, anti-fouling
      agent or thermic stabilizant); polybrominated diphenyl ethers (PBDE, fire retardants);
      perchlorated octanoïd acid and its sulphated compounds (PFOA and PFOS, perfluoroalkyls used
      as surfactant, lubrifiants, and usted in wrappings); and organochorinated compounds such as:
      PCB153, representing the polychlorinated bisphenyls (electric isolation); hexachlorobenzene
      (HBC), and several pesticides: DDE, metabolite of DDT, now banned but with a very long half
      life, hexachlorocyclohexane (HCH), heptachlor, nanochlor and chlordane used in agriculture.

      II- Originality and /or new aspect of the project Though suggested by several experimental
      studies, the role of POP in human obesity remains largely unknown.

      There are no or very few papers on the role in humans of the POPs we have selected, but they
      are supported by animal experimental studies.

      The concept of release in the blood stream after weight loss is recent and deserves to be
      studied.

      III- Reasons for the choice of questions (3 maximum) Interest of the results/method to
      improve knowledge on those questions

        1. To study the kinetics of release after bariatric surgery of selected polluants stored in
           adipose tissue, looking for clinical and/or predictive factors

        2. To test the hypothesis of a deleterious effect of this release on the expected
           improvement of insulin-resistance and on the liver inflammation.

        3. To determine the level of contamination of morbidly obese patients, with or without
           metabolic syndrome, compared to a control, non obese population, with special attention
           to clinical (age, gender, reproductive history, pregnancy, nursing) and biological
           parameters (insulin-resistance, inflammation).

      IV- Description of the methods/ Calendar The POPs will be measured in serum, urine (for BPA)
      and in adipose tissue (subcutaneous and visceral) by gas chromatography coupled to mass
      spectrometry.

      Fat mass will be estimated when possible by DEXA (if weight<150 kg), or by impedancemetry,
      allowing the calculation of an estimated total body burden for each POP (since they are
      lipophilic, we will multiply the concentration of each chemical in adipose tissue expressed
      in ng/g of fat by the total estimated body mass of fat).

      The number of patients included will be 250 morbidly obese adults, with or without metabolic
      syndrome (3 out of 5 classical criteria), eligible for bariatric surgery (125 from Nice
      undergoing gastric bypass, and 125 from Montpellier undergoing sleeve gastrectomy).

      Concentrations of polluants will be measured at baseline and 3, 6 and 12 month after
      bariatric surgery, and at 18 months as well for patients who will undergo abdominoplasty
      required by their massive weight loss. Baseline concentrations in obese patients will be
      compared to those measured in 100 controls, matched for age and gender, with a BMI<25.

      Insulin resistance will be assessed by HOMA-IR, adiponectine and SHBG, inflammation by us
      CRP, leptin, interleukin 6, TNF alpha, transaminases, gammaGT, alkalin phosphatase.

      The redistribution of POPs in serum and adipose tissue, and the estimation of total body
      burden will be assessed before and after surgery.
    

Intervention name(s): Lipophilic Organic Polluants dosage
Intervention type(s): Other
Intervention description(s): Urinary, blood and fat dosage of Lipophilic Organic Polluants
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science