Insulin Regulation of Lipolysis and Lipolysis Proteins
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
-
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.
-
The investigators will determine whether the improved insulin regulation of lipolysis resulting from treatment with the PPARĪ³ agonist pioglitazone, with or without weight loss, can be linked to specific changes in sets of PPARĪ³-responsive adipocyte lipolysis proteins in UBO adults.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Immediate weight loss - placebo Upper body obese participants randomized to this group; all will begin their immediate participation in a comprehensive lifestyle obesity treatment program after completion of baseline studies. Half of the volunteers will be randomized to placebo during this period. |
Behavioral: Immediate 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.
Drug: Placebo
Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.
|
| Placebo Comparator: Deferred control group - placebo After baseline studies, UBO participants randomized to this group will wait without any intervention for 4 months, with continued monitoring to assure weight stability - this group will be the half of volunteers randomized to deferred weight loss intervention that are also randomized to placebo. At the end of this 'wait' period they will be enrolled in the same comprehensive lifestyle obesity treatment program for 4 months, but without placebo. |
Behavioral: Deferred 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.
Drug: Placebo
Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.
|
| Active Comparator: Immediate weight loss - pioglitazone Upper body obese participants randomized to this group; all will begin their immediate participation in a comprehensive lifestyle obesity treatment program after completion of baseline studies. Half of the volunteers will be randomized to pioglitazone during this period. |
Behavioral: Immediate 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.
Drug: Pioglitazone
Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.
|
| Active Comparator: Deferred group - pioglitazone After baseline studies, UBO participants randomized to this group will wait without any intervention for 4 months, with continued monitoring to assure weight stability - this group will be the half of volunteers randomized to deferred weight loss intervention that are randomized to pioglitazone. They will be monitored to prevent the usual but modest weight gain associated with pioglitazone. They will be on pioglitazone during the 'wait' period. At the end of this 'wait' period they will be enrolled in the same comprehensive lifestyle obesity treatment program for 4 months, but without pioglitazone. |
Drug: Pioglitazone
Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.
Behavioral: Deferred 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.
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic in Rochester | Rochester | Minnesota | United States | 55905 |
Sponsors and Collaborators
- Mayo Clinic
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
- Principal Investigator: Michael D Jensen, Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 17-009837
- 2R01DK040484-30