NCT03866408 - Insulin Regulation of Lipolysis and Lipolysis Proteins | Crick

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

64

Conditions

Obesity

Interventions

Immediate weight lossBEHAVIORAL

Upper body obese subjects will undergo behavioral intervention with a life coach and a physical activity program of their choice for 4 months.

PioglitazoneDRUG

Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.

Deferred weight lossBEHAVIORAL

Upper body obese subjects will complete a weight-stable period of 4 months and subsequently undergo behavioral intervention with a life coach and a physical activity program of their choice for 4 months.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Mayo Clinic in Rochester

Rochester, Minnesota, United States

RECRUITING

Outcomes

Primary Outcomes

Adipocyte response to insulin - perilipin 1 and FSP27 relative to HSL and ATGL

In response to weight maintenance vs. weight loss with pioglitazone vs. placebo, insulin regulation of lipolysis in upper body obese as measured by insulin IC50 for palmitate flux and compared to adipocyte perilipin 1 and FSP27 relative to HSL and ATGL.

Time frame: 4-9 months

Adipocyte response to insulin - adipocyte G0S2 relative to ATGL.

In response to weight maintenance vs. weight loss with pioglitazone vs. placebo, insulin regulation of lipolysis in upper body obese as measured by insulin IC50 for palmitate flux and compared to adipocyte G0S2 relative to ATGL.

Time frame: 4-9 months

Adipocyte response to insulin - adipocyte CGI-58 relative to ATGL

In response to weight maintenance vs. weight loss with pioglitazone vs. placebo, insulin regulation of lipolysis in upper body obese as measured by insulin IC50 for palmitate flux and compared to adipocyte CGI-58 relative to ATGL.

Time frame: 4-9 months

Adipocyte response to insulin - perilipin 1, ATGL and HSL phosphorylation

In response to weight maintenance vs. weight loss with pioglitazone vs. placebo, insulin regulation of lipolysis in upper body obese as measured by insulin IC50 for palmitate flux and compared to adipocyte perilipin 1, ATGL and HSL phosphorylation in response to insulin.

Time frame: 4-9 months