Inflammation Regulation in Obese Patients
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Obesity Insulin Resistance |
Other: muscle and fat biopsy |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label |
| Official Title: | Relations Between Obesity and Insulin Resistance: Role of Inflammation Regulatory Mechanisms in Obese Patients Without Associated Comorbidity |
- TLR regulation [ Time Frame: 2 years ] [ Designated as safety issue: No ]analyse the role of RLI and RNase L in TLR regulation, and its potential implication in the link between obesity, microinflammation and insulin resistance in adipose tissue and squelettal muscle in humans.
| Estimated Enrollment: | 30 |
| Study Start Date: | November 2011 |
| Estimated Study Completion Date: | November 2013 |
| Primary Completion Date: | November 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: volunteers
not overweight Volunteers responding to the study criteria
|
Other: muscle and fat biopsy
muscle and fat biopsy
|
|
Experimental: overweight patients insulin sensitive
overweight patients insulin sensitive responding to the study criteria
|
Other: muscle and fat biopsy
muscle and fat biopsy
|
|
Experimental: overweight insulin resistant
overweight patients insulin resistant responding to the study criteria
|
Other: muscle and fat biopsy
muscle and fat biopsy
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 50 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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
Contacts and Locations| Contact: Ariane Sultan, MCU-PH | a-seddiki@chu-montpellier.fr |
| France | |
| Montpellier University Hospital | Recruiting |
| Montpellier, France, 34295 | |
| Principal Investigator: Ariane Sultan, MCU-PH | |
| Study Chair: | Jacques Mercier | University Hospital, Montpellier |
More Information
No publications provided
| Responsible Party: | University Hospital, Montpellier |
| ClinicalTrials.gov Identifier: | NCT01561664 History of Changes |
| Other Study ID Numbers: | UF 8685 |
| Study First Received: | March 6, 2012 |
| Last Updated: | March 21, 2012 |
| Health Authority: | France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) |
Keywords provided by University Hospital, Montpellier:
|
obesity insulin resistance |
Additional relevant MeSH terms:
|
Inflammation Insulin Resistance Obesity Pathologic Processes Hyperinsulinism Glucose Metabolism Disorders Metabolic Diseases Overnutrition |
Nutrition Disorders Overweight Body Weight Signs and Symptoms Insulin Hypoglycemic Agents Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 21, 2013