Salsalate Treatment Improves Glycemia Without Altering Adipose Tissue in Non-Diabetic Obese Hispanics

OBJECTIVE: Salsalate treatment has well-known effects on improving glycemia and the objective of this study was to examine whether the mechanism of this effect is related to changes in adipose tissue. METHODS: We conducted a randomized double-blind and placebo-controlled trial in obese Hispanics (18-35 years). The intervention consisted of 4 g/day of salsalate (n=11) versus placebo (n=13) for 4 weeks. Outcome measures included glycemia, adiposity, ectopic fat, and adipose tissue gene expression and inflammation. RESULTS: In those receiving salsalate, plasma fasting glucose decreased by 3.4% (P<0.01), free fatty acids decreased by 42.5% (P=0.06) and adiponectin increased by 27.7% (P<0.01). Salsalate increased insulin AUC by 38% (P=0.01) and HOMA-B by 47.2% (P<0.01) while estimates of insulin sensitivity/resistance were unaffected. These metabolic improvements occurred without changes in total, abdominal, visceral, or liver fat. Plasma markers of inflammation/immune activation were unchanged following salsalate. Salsalate had no effects on adipose tissue including adipocyte size, presence of crown-like structures, or gene expression of adipokines, immune cell markers, or cytokines downstream of NF-κB with the exception of downregulation of IL-1β (P<0.01). CONCLUSIONS: Our findings suggest that metabolic improvements in response to salsalate occurred without alterations in adiposity, ectopic fat, or adipose tissue gene expression and inflammation.