Colchicine's effects on metabolic and inflammatory molecules in adults with obesity and metabolic syndrome: results from a pilot randomized controlled trial

Andrew P Demidowich, Jordan A Levine, Richard Apps, Foo K Cheung, Jinguo Chen, Giovanna Fantoni, CHI Consortium, Tushar P Patel, Jack A Yanovski, Huizhi Zhou, Rongye Shi, Poorani Subramanian, John Tsang, Yasmine Belkaid, Andrew P Demidowich, Jordan A Levine, Richard Apps, Foo K Cheung, Jinguo Chen, Giovanna Fantoni, CHI Consortium, Tushar P Patel, Jack A Yanovski, Huizhi Zhou, Rongye Shi, Poorani Subramanian, John Tsang, Yasmine Belkaid

Abstract

Objective: Recent clinical trials have demonstrated that colchicine may have metabolic and cardiovascular and benefits in at-risk patients; however, the mechanisms through which colchicine may improve outcomes are still unclear. We sought to examine colchicine's effects on circulating inflammatory and metabolic molecules in adults with obesity and metabolic syndrome (MetS).

Methods: Blood samples were collected pre- and post-intervention during a double-blind randomized controlled trial in which 40 adults with obesity and MetS were randomized to colchicine 0.6 mg or placebo twice-daily for 3 months. Serum samples were analyzed for 1305 circulating factors using the SomaScan Platform. The Benjamini-Hochberg procedure was used to adjust the false discovery rate (FDR) for multiple testing.

Results: At baseline, age (48.0 ± 13.8 vs. 44.7 ± 10.3 years) and BMI (39.8 ± 6.4 vs. 41.8 ± 8.2 kg/m2) were not different between groups. After controlling for the FDR, 34 molecules were significantly changed by colchicine. Colchicine decreased concentrations of multiple inflammatory molecules, including C-reactive protein, interleukin 6, and resistin, in addition to vascular-related proteins (e.g., oxidized low-density lipoprotein receptor, phosphodiesterase 5A). Conversely, relative to placebo, colchicine significantly increased concentrations of eight molecules including secreted factors associated with metabolism and anti-thrombosis.

Conclusions: In adults with obesity, colchicine significantly affected concentrations of proteins involved in the innate immune system, endothelial function and atherosclerosis, uncovering new mechanisms behind its cardiometabolic effects. Further research is warranted to investigate whether colchicine's IL-6 suppressive effects may be beneficial in COVID-19.

Conflict of interest statement

The authors have no conflict of interest to disclose. JAY receives grant support for unrelated studies sponsored by Rhythm Pharmaceuticals Inc., and by Soleno Therapeutics Inc.

Figures

Fig. 1. Changes in Selected Circulating Biomarkers.
Fig. 1. Changes in Selected Circulating Biomarkers.
Selected circulating biomarkers that were significantly a decreased or b increased in the colchicine arm as compared with placebo after adjustment for the false discovery rate. Bars represent median values, whiskers represent the 95% confidence interval. All values are expressed as relative fluorescence units.

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Source: PubMed

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