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

X

Xiang Guang-da

Status and phase

Completed
Phase 4

Conditions

Obesity

Treatments

Drug: Exenatide
Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02170324
2014Wze091

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 patients

Sex

Male

Ages

20 to 30 years old

Volunteers

No 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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

20 participants in 2 patient groups, including a placebo group

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

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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