mTOR and Adipose Tissue Inflammation

Completed

• Conditions: Obesity
• Interventions: Other: Adipose tissue sampling

• Registration Number: NCT02881697
• Lead Sponsor: University Hospital, Basel, Switzerland

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-08-18
• Study First Submitted QC: 2016-08-23
• Study First Posted: 2016-08-29
• Study Start: 2016-09-27
• Primary Completion: 2019-04-23
• Study Completion: 2019-07-27
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-12
• Last Update Posted: 2019-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
mTORC2 activity in adipose tissue measured by immunoblot	single time point at surgery	measurement of mTORC2 activity in adipose tissue once at surgery

Secondary Outcome Measures

Name	Time	Method
Mcp1 messenger ribonucleic acid (mRNA) level in adipose tissue measured by quantitative polymerase chain reaction (PCR)	single time point at surgery	measurement of Mcp1 messenger ribonucleic acid (mRNA) level in adipose tissue once at surgery