Long-term, Substantial Weight Loss and Insulin Regulation of Lipolysis

Study Overview
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Brief Summary
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It is not known how much improvement in insulin regulated lipolysis (the breakdown of triglycerides) occurs following substantial, sustained weight loss. Researchers will test the effects of inflammation and lipolysis regulation in people before and after bariatric surgery (sleeve gastrectomy) to answer these questions.

Detailed Description
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The purpose of this study is to determine whether the adipose inflammatory cell and cytokine content in Class III obesity is related to lipolysis insulin resistance and, if so, whether sustained, substantial weight loss one year following bariatric surgery reduces inflammation in parallel with improved insulin regulation of lipolysis

Official Title
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Long-term, Substantial Weight Loss and Insulin Regulation of Lipolysis

Conditions
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Obesity, Morbid

Intervention / Treatment
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* Procedure: Gastric sleeve/bariatric surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI 40 - 50 kg/m2. Mo active physical illness that would interfere with mobility or weight loss after bariatric surgery Exclusion Criteria: Type 1 or Type 2 Diabetes diagnosis or fasting plasma glucose ≥126 mg/dL Active coronary artery disease Participation in structured exercise (>2 times per week for 30 minutes or longer) Smoking Medications known to affect adipose tissue metabolism (e.g., beta blockers, corticosteroids) Renal insufficiency (serum creatinine > 1.5mg/dl) Chronic active liver disease (Bilirubin > 17mmol/L, AST > 144 IU/L, or ALT>165IU/L) Pregnancy or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Study insulin action and adipose function before and after weight loss from gastric sleeve surgery
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gastric sleeve surgery<br>before and after weight loss from bariatric surgery | Procedure: Gastric sleeve/bariatric surgery<br>* weight loss<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adipose macrophage content, adipose IL-6 and TNF gene expression | Adipose tissue macrophage content as assessed by immunohistochemistry using stains for CD36, CD14 and CD206 will be done. mRNA expression for IL-6 and TNF will be measured | Before bariatric surgery and approximately 1 year after surgery | 
| insulin regulation of lipolysis (IC50) | The ability of insulin to suppress FFA palmitate release will be assessed using a 2-step insulin clamp and isotope dilution techniques for palmitate kinetics | Before bariatric surgery and approximately 1 year after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adipocyte perilipin 1 and HSL and ATGL | These proteins will be measured using capillary Western methods. | Before bariatric surgery and approximately 1 year after surgery |