Using Salsalate to Target Adipocyte Macrophage Infiltration and Reverse Metabolic Disease Risk in Obese Hispanic Young Adults
Description
Brief Summary
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.
Phase
OtherInclusion and Exclusion Criteria
- Obese (body mass index >30 kg/m^2)
- Hispanic males and females age 18-35 years
- Women with hemoglobin <11.5 g/dL or men with hemoglobin <12.5 g/dL will be excluded
- AST / ALT >2 times the upper limit of normal
- Evidence of any liver disease other than non-alcoholic steatosis
- Diabetes
- Diagnosis of any disease that is known to influence insulin action and secretion
- Current or past involvement in any weight loss, exercise, or sports program in the six months prior to participation
- Use of medication known to influence body composition or fat distribution (e.g. Cushing syndrome)
- History of renal disease
- Use of non-steroidal anti-inflammatory drugs (NSAIDs)
- Chicken pox, flu, or influenza infection
- Those taking high doses of vitamin C, antacids (containing Ca2+ or Mg+2), or taking Warfarin
- Hypertension
- Allergies to Salsalate, aspirin or other NSAIDs
- History of peptic ulcer or upper GI bleeding
- A positive pregnancy test or current lactation
- Has smoked greater than 100 cigarettes in their lifetime and now smokes everyday or some days
- Drinks greater than 200 g/day of alcohol
- Those with a waist circumference (or widest part of body measurement) greater than or equal to 185 cm due to MRI size restrictions
Sites
-
California
- University of Southern California Diabetes Obesity Research Institute (DORI), Los Angeles, California, 90089
- University of Southern California, Clinical Trials Unit (CTU), Los Angeles, California, 90089