Clinical trial NCT03866408: Insulin Regulation of Lipolysis and Lipolysis Proteins
Official title: Insulin Regulation of Lipolysis and Lipolysis Proteins
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Obesity
Keywords: adipose tissue
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2019-03-07
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: immediate weight loss (placebo) will be compared with deferred weight loss (placebo) to determine the effects of weight loss alone immediate weight loss placebo will be compared with deferred weight loss pioglitazone to determine the effects of weight loss vs. pioglitazone deferred weight loss placebo will be compared with deferred weight loss pioglitazone to determine the effects of pioglitazone alone deferred weight loss placebo will be compared with deferred weight loss pioglitazone to determine the effects of weight loss alone vs. previous exposure to pioglitazone immediate weight loss placebo and deferred weight loss placebo will be pooled to create a larger group to determine the effects of weight loss on outcome variables
Primary purpose: BASIC_SCIENCE

Brief summary: These studies will define the abnormalities in the adipocyte proteins that are involved in the failure of insulin to suppress lipolysis normally in humans with upper body obesity and will help discover the mechanism by which pioglitazone, a medication used to treat type 2 diabetes and improve insulin resistance, improves insulin-regulation of adipocyte fatty acid metabolism.

Detailed description: 1. The investigators will determine whether impaired insulin-induced suppression of lipolysis (as measured by IC50) is related to the above mentioned lipolysis proteins in groups of volunteers known to vary widely with regards to abdominal adipocyte size and regulation of adipose tissue lipolysis.
2. The investigators will determine whether the improved insulin regulation of lipolysis resulting from treatment with the PPARγ agonist pioglitazone, with or without weight loss, can be linked to specific changes in sets of PPARγ-responsive adipocyte lipolysis proteins in UBO adults.

Eligibility criteria: Inclusion Criteria:

* Men and Women between the ages of 18 and 55.
* Women will be premenopausal
* Non obese adults BMI between 18-25
* Obese BMI 30-38

Exclusion Criteria, Pioglitazone package insert of contraindications for use:

* Initiation in patients with established New York Heart Associations (NYHA) class III or IV Heart failure.
* Use in patients with known hypersensitivity to pioglitazone or any other component of ACTOSE.

Primary outcomes:
measure: Adipocyte response to insulin - perilipin 1 and FSP27 relative to HSL and ATGL
timeFrame: 4-9 months
measure: Adipocyte response to insulin - adipocyte G0S2 relative to ATGL.
timeFrame: 4-9 months
measure: Adipocyte response to insulin - adipocyte CGI-58 relative to ATGL
timeFrame: 4-9 months
measure: Adipocyte response to insulin - perilipin 1, ATGL and HSL phosphorylation
timeFrame: 4-9 months
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael D Jensen
role: PRINCIPAL_INVESTIGATOR
References: