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Salsalate improves glycemia in obese Hispanics without adipose tissue changes
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Metabolic improvements with salsalate therapy appear to occur without changes in adiposity, ectopic fat or adipose tissue gene expression and inflammation, according to research published in Obesity.
“Similar to previous salsalate studies, treatment improved fasting blood glucose, insulin, and fasting free fatty acids in obese nob-diabetic Hispanics who are at increased risk for metabolic disease,” Michael I. Goran, PhD, of the Keck School of Medicine, University of Southern California, Los Angeles, told Endocrine Today. “We found that these improvements occurred without changes in adiposity, including fat distribution, ectopic fat, adipocyte size, and adipose tissue gene expression of adipokines and markers of adipose tissue inflammation.”
Michael I. Goran
Goran, with Tanya L. Alderete, PhD, a postdoctoral scholar research associate at the university, with and colleagues, conducted a double blind, placebo-controlled trial in Hispanics aged 18 to 35 years with obesity.
To examine whether improved glycemic effects seen with salsalate treatment are related to changes in adipose tissue, the researchers randomly assigned patients to 2 g twice-daily salsalate (n = 11) vs. placebo (n = 13) for 4 weeks.
The investigators assessed glycemia, adiposity, ectopic fat and adipose tissue gene expression and inflammation for outcomes.
Plasma fasting glucose dropped by 3.4% (P < .01) with salsalate; free fatty acids also decreased. Adiponectin rose by 27.7% (P < .01), insulin area under the curve by 38% (P = .01) and homeostasis model assessment for beta-cell function by 47.2% (P < .01); insulin sensitivity/resistance estimates appeared unaffected.
Tanya L. Alderete
The metabolic improvements with treatment occurred without alterations in total, abdominal, visceral or liver fat.
With salsalate, plasma markers of inflammation/immune activation also were unchanged. Treatment did not affect adipose tissue, including size of adipocytes, presence of crown-like structures or gene expression of adipokines; further, no effect was seen on immune cell markers or cytokines downstream of nuclear factor-kappa binding, except for the downregulation of interleukin-1 beta (P < .01).
“This study suggests that mechanism(s), other than changes in adiposity or inflammation, contribute to decreased blood glucose levels with salsalate treatment,” Goran said. “Consequently, treatment with salsalate may not be ideal for dampening obesity-associated inflammation in an effort to decrease disease risk.”
Future investigation should incorporate similar measures of adiposity and adipose tissue inflammation and examine how salsalate affects the liver including hepatic insulin sensitivity and glucose production, along with insulin and adiponectin clearance.
“Quantification of immune cells in adipose tissue, beyond monocytes/macrophages, would be important since changes in pro-inflammatory macrophages or regulatory T cells or may occur with salsalate,” Goran said. “It would be useful to identify other anti-inflammatory medications that could also dampen the inflammatory response associated with increased obesity.” – by Allegra Tiver
For more information:
Michael I. Goran, PhD, can be reached at 2250 Alcazar, CSC Bldg #212, Los Angeles, CA 90033; email: goran@usc.edu.
Disclosure: The researchers report no relevant financial disclosures.
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