GLP-1 Agonism Stimulates Browning of Subcutaneous White Adipose Tissue in Obesity Men

Sponsor

Xiang Guang-da (Other)

Overall Status

Completed

CT.gov ID

NCT02170324

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Adipose tissues, which include white adipose tissue (WAT) and brown adipose tissue (BAT), play an essential role in regulating whole-body energy homeostasis. Excess expansion of WAT due to positive energy balance and defects in thermogenic gene expression in BAT are associated with obesity and various metabolic diseases. Until 2009 the question of whether adult humans had BAT and whether it could conceivably contribute to whole body energy usage in a meaningful way was a matter of vigorous debate. The publication of three apppers in the New England Journal of Medicine that demonstrated adult humans do have BAT, that it can be activated, and that this activation appears to be defective in obesity reframed the debate, and revived interest in BAT physiology. Recent studies also reveal the presence of a subset of cells in WAT that could be induced by environmental or hormonal factors to become ''brown-like'' cells, and this ''beigeing'' process has been suggested to have strong antiobesity and antidiabetic benefits.

The extrapancreatic actions of glucagon-like peptide-1 (GLP-1) on endothelial cells and the liver have been reported. Additionally, effects of GLP-1 on adipose tissue have been described. Studies performed in isolated adipocytes have demonstrated that GLP-1 has the ability to induce both lipogenic and lipolytic mechanisms in white adipose tissue (WAT) . More recent study showed that GLP-1 agonism stimulates brown adipose tissue thermogenesis and browning through hypothalamic AMP-activated protein kinase (AMPK) in animal. However, there is no data clearly show that GLP-1 agonism stimulates browning of subcutaneous white adipose tissue (SWAT) in human obesity.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Exenatide Drug: Placebo	Phase 4

Detailed Description

Individuals were treated for 10 days. Biopsy for subcutaneous white adipose (1.5X1.5X1.5cm) was performed before and after 10 days treatment programme under local anesthesia. Measure the brown fat characteristics of biopsy samples.The sample was immediately processed in 3 sections.One part was stored for immunohistology and western blot, the second was snap-frozen for estimation of biochemical markers, and the remainder was used to harvest small subcutaneous arteries with micro-dissection. Also, the perivascular adipose tissue (PVAT) was studied on the changes of morphology and possible signal pathways before and after GLP-1 treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Study Start Date :

Jun 1, 2014

Actual Primary Completion Date :

Jul 1, 2015

Actual Study Completion Date :

Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GLP-1 agonism group Exenatide injection 10 ug twice daily for 10 days subcutaneously.	Drug: Exenatide
Placebo Comparator: Placebo group 0.9 % sodium choride 0.1 ml twice daily for 10 days subcutaneously.	Drug: Placebo

Arm

Intervention/Treatment

Experimental: GLP-1 agonism group

Exenatide injection 10 ug twice daily for 10 days subcutaneously.

Drug: Exenatide

Placebo Comparator: Placebo group

0.9 % sodium choride 0.1 ml twice daily for 10 days subcutaneously.

Drug: Placebo

Outcome Measures

Primary Outcome Measures

The expression of brown adipose related genes in subcutaneous white adipose tissue [3 months]
Brown fat characteristics of biopsy samples will be assessed by determining the expression levels of uncoupling protein-1 (UCP-1), peroxisome proliferator-activated receptor (PPAR)-r, peroxisome proliferator-activated receptor r coactivator 1 a (PGC1a) , growth factor receptor binding protein-10 (Grb10), PR domain containing 16 (PRDM16); In addition, a combination of PET and computed tomography (CT) - with the glucose analogue 18F-fluorodeoxyglucose (18F-FDG) as a tracer will be performed for brown adipose tissue before and after GLP-1 agonism treatment programme.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 30 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Body mass index (BMI) > 30 kg/m2
Men
Age 20 - 30 years old

Exclusion Criteria:

BMI < 30 kg/m2
Diabetes
Hypertension
Use of medicines

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wuhan General Hospital	Wuhan	Hubei	China	430070

Sponsors and Collaborators

Xiang Guang-da

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Xiang Guang-da, Director of Endocrinology Dept., Wuhan General Hospital of Guangzhou Military Command

ClinicalTrials.gov Identifier:

NCT02170324

Other Study ID Numbers:

2014Wze091

First Posted:

Jun 23, 2014

Last Update Posted:

Jan 18, 2017

Last Verified:

Jan 1, 2017

Additional relevant MeSH terms:

Obesity

Exenatide

Study Results

No Results Posted as of Jan 18, 2017