Obesity
Conditions
Keywords
adipose tissue
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.
Interventions
BEHAVIORALImmediate weight loss
Upper body obese subjects will undergo behavioral intervention with a life coach and a physical activity program of their choice for 4 months.
DRUGPioglitazone
Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.
BEHAVIORALDeferred weight loss
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.
DRUGPlacebo
Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.
Sponsors
Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
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
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adipocyte response to insulin - perilipin 1 and FSP27 relative to HSL and ATGL | 4-9 months | 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. |
| Adipocyte response to insulin - adipocyte G0S2 relative to ATGL. | 4-9 months | 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. |
| Adipocyte response to insulin - adipocyte CGI-58 relative to ATGL | 4-9 months | 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. |
| Adipocyte response to insulin - perilipin 1, ATGL and HSL phosphorylation | 4-9 months | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichael D Jensen
Mayo Clinic
Outcome results
None listed