mTOR and Adipose Tissue Inflammation

mTOR and Adipose Tissue Inflammation in Humans

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: Adipose tissue sampling

• Study Type: Observational
• Enrollment (Actual): 80

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Obese patients (BMI >35 kg/m2) with insulin resistance and lean controls (BMI < 27kg/m2) scheduled for elective surgery for non-inflammatory conditions such as gallstone disease, diverticular disease or - in the case of obese subjects - bariatric surgery

Description

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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Obese insulin-resistant subjects; 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
Lean insulin-sensitive controls; 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
Obese diabetic subjects; 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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin resistance measured with fasting plasma insulin and fasting glucose	measurement of fasting plasma insulin and fasting Glucose once at surgery	single time point at surgery

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Study Chair: Christoph Beglinger, MD, St. Claraspital klinische Forschungsabteilung

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2016
• Primary Completion (Actual): April 23, 2019
• Study Completion (Actual): July 27, 2019

Study Registration Dates

• First Submitted: August 18, 2016
• First Submitted That Met QC Criteria: August 23, 2016
• First Posted (Estimate): August 29, 2016

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: mTOR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED