using salsalate to target adipocyte macrophage infiltration

Conditions: Diabetes Risk

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.


Eligibility criteria:
inclusion criteria: * obese (body mass index \>30 kg/m\^2) * hispanic males and females age 18-35 years exclusion criteria: * 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

Keywords: obesity adipose tissue inflammation salsalate hispanics