Salsalate treatment improves glycemia without altering adipose tissue in nondiabetic obese hispanics

Abstract

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.

Effect of Dietary Content of Menhaden Oil with or without Salsalate on Neuropathic Endpoints in High-Fat-Fed/Low-Dose Streptozotocin-Treated Sprague Dawley Rats

“…In humans with type 2 diabetes, salsalate, 3.5 g/day, improved glycemia and decreased inflammatory markers [ 17 ]. In obese, insulin-resistant, nondiabetic subjects, salsalate reduced the atherogenicity of the lipid, lipoprotein, and apoprotein profile and insulin sensitivity [ 30 , 31 ]. In animal studies, salsalate has been shown to reduce vascular injury in Zucker fatty rats and activate skeletal muscle thermogenesis and protect C57Bl/6J mice from a high-fat diet [ 32 , 33 ].…”

Adipose tissue inflammation in breast cancer survivors: effects of a 16-week combined aerobic and resistance exercise training intervention

“…After anesthetizing the skin at the biopsy site (right anterior axillary line, level of the umbilicus) with 1% lidocaine injection, a 6 mm Bergstrom biopsy needle was introduced through a 6-7 mm incision in the abdominal skin. Manual suction from a 60cc syringe attached via tubing to the inner bore of the biopsy needle was applied to pull tissue into the side cutting window which was then sheared with the inner trochar (20). Adipose tissue was rapidly irrigated with iced saline and immediately transported to the laboratory, where it was sectioned and processed for further analysis.…”

Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus

“…Aspirin reduces blood glucose in patients with T2DM (390) but not in individuals with normal glucose tolerance (142, 337). More recently, several studies, including six randomized, blinded and placebo controlled trials, demonstrated marked improvements in glucose tolerance and reduced HbA1c with salsalate treatment among obese patients with and without T2DM (13, 117, 130, 143–145, 196). In addition, in five of the six trials, salsalate treatment reduced markers of systemic inflammation (CRP, IL-6, or CD40L) or increased adiponectin (13, 130, 143, 145, 196).…”