Colchicine's effects on metabolic and inflammatory molecules in adults with obesity and metabolic syndrome: results
Andrew P Demidowich1,2,3,4, Jordan A Levine5, Richard Apps6
1Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892-1103, USA. ademido1@jh.edu.
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.
Insights
Colchicine treatment in adults with obesity and metabolic syndrome reduced inflammatory molecules and affected proteins involved in endothelial function and atherosclerosis, revealing potential cardiometabolic benefits. Further research is needed to explore its effects on COVID-19.
Area of Science:
- Cardiovascular Medicine
- Metabolic Disorders
- Immunology
Background:
- Colchicine shows potential metabolic and cardiovascular benefits in at-risk patients.
- Mechanisms underlying colchicine's positive effects are not fully understood.
- Obesity and metabolic syndrome (MetS) are associated with increased cardiovascular risk.
Purpose of the Study:
- To investigate colchicine's impact on circulating inflammatory and metabolic molecules.
- To explore potential mechanisms of colchicine's cardiometabolic effects in adults with obesity and MetS.
Main Methods:
- A double-blind randomized controlled trial involving 40 adults with obesity and MetS.
- Participants received either colchicine (0.6 mg twice-daily) or placebo for 3 months.
- Serum samples analyzed for 1305 circulating factors using the SomaScan Platform, with FDR adjustment for multiple testing.
Main Results:
- Colchicine significantly altered 34 molecules compared to placebo.
- Decreased concentrations of inflammatory markers (C-reactive protein, interleukin-6, resistin) and vascular proteins (oxidized LDL receptor, PDE5A).
- Increased concentrations of eight molecules, including those related to metabolism and anti-thrombosis.
Conclusions:
- Colchicine impacts proteins in the innate immune system, endothelial function, and atherosclerosis in adults with obesity.
- These findings suggest novel mechanisms for colchicine's cardiometabolic effects.
- Investigating colchicine's IL-6 suppressive effects for potential benefits in COVID-19 is warranted.
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