Using Salsalate to Target Adipocyte Macrophage Infiltration
Status:
Completed
Trial end date:
2013-10-01
Target enrollment:
Participant gender:
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.