Inflammation Regulation in Obese Patients
Inflammation Regulation in Obese Patients
Insulin resistance is one of the main mechanisms involved in metabolic diseases. inflammation
 has been implicated in its pathogenesis, due to innate immunity activation by free fatty
 acids, lipopolysaccharides (LPS) and lactate. Free fatty acids, LPS and lactate activate
 innate immunity in squelettal muscle and adipose tissue via Toll-like receptor 2/4, NFkB,
 IRF3 (Interferon Responsive Factor 3) and cytokines secretion (TNFa, IFN g, IL1b, IL6),
 chemokines secretion (MCP1) and leukotrienes (LTB4). Feed back mechanisms involved in TLR
 signaling pathways as RLI (ribonuclease L inhibitor)/ABCE1, have never been studied in
 inflammation due to obesity. RLI inhibits an endoribonuclease, RNase L, which has been
 recently implicated in TLR signaling The purpose of this study is to analyse the role of RLI
 and RNase L in TLR regulation, and its potential implication in the link between obesity,
 inflammation and insulin resistance in adipose tissue and squeletal muscle in humans.
The investigators working hypothesis is that RNase L and RLI contribute to chronic
 inflammation regulation and to insulin response through TLR 4 pathway regulation in obesity.
 The investigators main purpose is to compare innate immunity activation pathway between
 insulin sensitive, insulin resistant obese patients and control patients. Insulin sensitive
 and insulin resistant obese patients will be distinguish thanks to the HOMA ir index. The
 investigators second objectives are to evaluate if the degree of inflammation in adipose
 tissue and squeletal muscle is correlated to insulin sensitivity measured by hyperinsulinemic
 euglycemic clamp and to characterise inflammatory pathway and regulation pathway. A special
 focus will be given to the leukotrienes and their potential role in insulin resistance
 pathogenesis. The investigators will have two approaches:- characterisation of subjects with
 normal weight, of obese insulin sensitive and obese insulin resistant through a metabolic
 evaluation, an inflammatory characterisation and a measure of insulin sensitivity at the
 systemic level, in adipose tissue and in squeletal muscle.- an in vitron approach with human
 myoblast and adipocytes culture, extracted from the investigators patients: characterisation
 of inflammation, innate immunity.
Inclusion Criteria:

 -  Age between 50 and 65 years old

 -  Men/ menopausal women

 -  BMI <25 kg/m2 for the control group, BMI >30 kg/m2 for the obese group

 -  Non diabetic patients

 -  HOMAIR <3 for the insulin sensitive obese group

 -  Non smoking

 -  Without any inflammatory disease

 -  Without any first degrees relative with diabetes

 -  Without any treatment that could interfere with insulin sensitivity

 -  without any infection