Hideo Makimura, Takara L. Stanley, Caroline Suresh, Ana Luisa De Sousa-Coelho, Walter R. Frontera, Stephanie Syu, Laurie R. Braun, Sara E. Looby, Meghan N. Feldpausch, Martin Torriani, Hang Lee, Mary-Elizabeth Patti, Steven K. Grinspoon
Abstract
Increased circulating free fatty acids (FFA) have been proposed to contribute to insulin resistance in obesity. Short-term studies have investigated the effects of acipimox, an inhibitor of hormone sensitive lipase, on glucose homeostasis, but longer term studies have not been performed.
To test the hypothesis that long term treatment with acipimox would reduce FFA and improve insulin sensitivity among nondiabetic, insulin resistant obese subjects.
At an academic medical center, 39 obese men and women were randomized to acipimox 250 mg thrice-daily vs. identical placebo for six months.
plasma lipids, insulin sensitivity, adiponectin, and mitochondrial function via assessment of the rate of post-exercise phosphocreatine recovery (PCr) on (31)P-magnetic resonance spectroscopy as well as muscle mitochondrial density and relevant muscle gene expression Results: Fasting glucose decreased significantly in acipimox-treated individuals (effect size -6mg/dL, p=0.02), in parallel with trends for reduced fasting insulin (effect size -6.8 μU/mL, p=0.07) and HOMA-IR (effect size -1.96, p=0.06) and significantly increased adiponectin (effect size +668 ng/mL, p=0.02). Acipimox did not affect insulin-stimulated glucose uptake, as assessed by euglycemic, hyperinsulinemic clamp. Effects on muscle mitochondrial function and density, and relevant gene expression were not seen.
These data shed light on the long term effects of FFA reduction on insulin sensitivity, other metabolic parameters, and muscle mitochondrial function in obesity. Reduced FFA achieved by acipimox improved fasting measures of glucose homeostasis, lipids and adiponectin, but had no effect on mitochondrial function, mitochondrial density, or muscle insulin sensitivity.
This research output has an Altmetric Attention Score of 25. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 December 2021.
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