mTOR and Adipose Tissue Inflammation

Study Overview
=================
Brief Summary
-----------------
The target of rapamycin complex 2 (TORC2) is an evolutionarily conserved serine/threonine protein kinase that controls growth and metabolism. In mammals (including humans), mammalian TOR complex 2(mTORC2) contains mammalian TOR (mTOR), RICTOR, mSIN1 protein, and mLST8 gene. In an animal model, the adipose-specific rictor knockout (AdRiKO) mouse, systemic insulin resistance, hepatic steatosis, and cardiovascular dysfunction develop upon high fat diet (HFD)-induced obesity or aging. To find a molecular link between adipose mTORC2 and systemic insulin resistance, investigators have already performed transcriptomics and proteomics analysis on visceral white adipose tissue in a mouse model. The aim of the study is to confirm a molecular link between adipose mTORC2 and systemic insulin resistance in humans.

Official Title
-----------------
mTOR and Adipose Tissue Inflammation in Humans

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Other: Adipose tissue sampling


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obese volunteers (BMI > 35kg/m2) aged 18 to a maximum of 60 years, males and females; insulin-resistant, scheduled for elective bariatric surgery. Normal weight patients (BMI < 27kg/m2) aged 18- max. 60 years, males and females; insulin-sensitive, scheduled for elective surgery. Exclusion Criteria: Known diabetes mellitus Chronic inflammatory disease (inflammatory bowel disease, rheumatoid disease, cancer) Acute inflammatory disease Known renal disease: kidney failure Pregnancy: history of gastrointestinal surgery with major changes to the gastrointestinal tract (removal of stomach, any GI-bypass) Substance abuse, alcohol abuse Inability to follow procedures due to psychological disorders, dementia insufficient knowledge of project language (German)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Obese insulin-resistant subjects<br>Adipose tissue sampling in obese volunteers (BMI > 35kg/m2) aged 18- max. 60 years, males and females; insulin-resistant, scheduled for elective bariatric surgery | Other: Adipose tissue sampling<br> <br> |
| Lean insulin-sensitive controls<br>Adipose tissue sampling in normal weight patients (BMI < 27kg/m2) aged 18- max. 60 years, males and females; insulin-sensitive, scheduled for elective surgery | Other: Adipose tissue sampling<br> <br> |
| Obese diabetic subjects<br>Adipose tissue sampling in obese volunteers (BMI > 35kg/m2) aged 18- max. 60 years, males and females; diabetic, scheduled for elective bariatric surgery | Other: Adipose tissue sampling<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mTORC2 activity in adipose tissue measured by immunoblot | measurement of mTORC2 activity in adipose tissue once at surgery | single time point at surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mcp1 messenger ribonucleic acid (mRNA) level in adipose tissue measured by quantitative polymerase chain reaction (PCR) | measurement of Mcp1 messenger ribonucleic acid (mRNA) level in adipose tissue once at surgery | single time point at surgery |