Background: The prevalence of obesity has increased throughout the last three decades due to genetic, metabolic, behavioral, and environmental factors. Obesity and high-fat western diets activate inflammatory processes, which promote development of insulin resistance as well as other metabolic complications. Increasing obesity rates are a major public health concern in the Hispanic population due to the large number of Hispanics suffering from obesity. Based on preliminary data, we propose a double-blind randomized clinical trial of Salsalate therapy in obese Hispanic young adults. Salsalate treatment shows promise for decreasing inflammation under conditions of weight stability by reducing macrophage infiltration of adipocytes. Hispanics have the greatest amount of visceral adipose tissue (VAT), liver fat, and inflammation when compared to other ethnic groups, thereby increasing the potential for treatment effects in this high-risk population. Purpose: The purpose of this study is to demonstrate through a "proof-of-concept" trial that Salsalate induced reductions in adipose tissue inflammation are possible under conditions of weight stability. Methodology: We will recruit obese Hispanic young adults (18 - 35 years) from hospitals, clinics, and community centers. Study Endpoints: Primary outcomes will be macrophage infiltration as assessed by the presence of crown-like structures (CLS) in subcutaneous adipose tissue (SAT) biopsies, liver fat, insulin sensitivity, and fasting glucose. We will also assess plasma levels of monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1, C-reactive protein (CRP), and SAT gene expression of nuclear factor kB (NF-kB) and insulin signaling pathways. Intervention and Follow-up: Participants will be randomly assigned to four weeks of treatment with Salsalate (4 g/d) or placebo and will be studied under weight maintenance conditions. These measures will enable us to determine if Salsalate treatment is capable of reducing adipose tissue inflammation and related metabolic outcomes in the absence of weight loss.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
30
Given orally twice daily
Given orally twice daily
University of Southern California Diabetes Obesity Research Institute (DORI)
Los Angeles, California, United States
University of Southern California, Clinical Trials Unit (CTU)
Los Angeles, California, United States
Change in plasma glucose levels over a 2-hour oral glucose tolerance test
Glucose following 4 weeks of treatment with salsalate (4 g/day) or placebo. A 2-hour oral glucose tolerance test will be performed at baseline and 4 weeks to measure changes in plasma glucose levels.
Time frame: 4 weeks
Change in adipose tissue inflammation
Adipose tissue inflammation following 4 weeks of treatment with salsalate (4 g/day) or placebo. Adipose tissue inflammation will be determined from abdominal subcutaneous adipose tissue biopsies performed at baseline and 4 weeks.
Time frame: 4 weeks
Change in systemic markers of inflammation
Systemic markers of inflammation following treatment with salsalate (4 g/day) or placebo. Fasting blood samples will be taken at baseline and 4 weeks to measure systemic markers of inflammation.
Time frame: 4 weeks
Change in plasma insulin levels over a 2-hour oral glucose tolerance test
Insulin following 4 weeks of treatment with salsalate (4 g/day) or placebo. A 2-hour oral glucose tolerance test will be performed at baseline and 4 weeks to measure changes in plasma insulin levels.
Time frame: 4 weeks
Change in plasma fasting free fatty acid levels
Fasting free fatty acids (FFA) following 4 weeks of treatment with salsalate (4 g/day) or placebo. Fasting blood samples will be taken at baseline and 4 weeks to measure changes in plasma fasting FFA.
Time frame: 4 weeks
Change in plasma C-peptide levels over a 2-hour oral glucose tolerance test
C-peptide following 4 weeks of treatment with salsalate (4 g/day) or placebo. A 2-hour oral glucose tolerance test will be performed at baseline and 4 weeks to measure changes in plasma C-peptide levels.
Time frame: 4 weeks
Change in body composition
Changes in body composition following 4 weeks of treatment with salsalate (4 g/day) or placebo. A DEXA scan will be performed at baseline and 4 weeks to measure any potential changes in body composition (body fat and lean tissue mass).
Time frame: 4 weeks
Change in ectopic fat
Changes in ectopic fat following 4 weeks of treatment with salsalate (4 g/day) or placebo. A 3-Tesla whole abdominal MRI scan will be performed at baseline and 4 weeks to measure any potential changes in ectopic fat.
Time frame: 4 weeks
Change in diet
Changes in diet following 4 weeks of treatment with salsalate (4 g/day) or placebo. A 24-hour diet recall will be performed at baseline and 4 weeks to measure any potential changes in diet.
Time frame: 4 weeks
Change in physical activity
Changes in physical activity following 4 weeks of treatment with salsalate (4 g/day) or placebo. A Godin-Shephard Leisure-Time Physical Activity questionnaire will be performed at baseline and 4 weeks to measure any potential changes in physical activity.
Time frame: 4 weeks
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