Jordan A Levine1, Zahra Sarrafan-Chaharsoughi1, Tushar P Patel1, Sheila M Brady1, K Karthik Chivukula1,2, Emily Miller1, Jung Min Han3, Vipul Periwal3, Anna Wolska4, Alan T Remaley4, Pradeep K Dagur5, Angelique Biancotto6, Ashley Babyak6, Giovanna Fantoni6, Jack A Yanovski1, Andrew P Demidowich1,7,8. 1. Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. 2. Clinical Endocrinology Section, Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. 3. Computational Medicine Section, Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. 4. Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. 5. Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. 6. Center for Human Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. 7. Johns Hopkins Community Physicians at Howard County General Hospital, Johns Hopkins Medicine, Columbia, Maryland, USA. 8. Department of Endocrinology, Diabetes and Metabolism, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Abstract
OBJECTIVE: The aim of this study was to examine whether colchicine's anti-inflammatory effects would improve measures of lipolysis and distribution of leukocyte populations in subcutaneous adipose tissue (SAT). METHODS: A secondary analysis was conducted for a double-blind, randomized, placebo-controlled pilot study in which 40 adults with obesity and metabolic syndrome (MetS) were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. Non-insulin-suppressible (l0 ), insulin-suppressible (l2 ), and maximal (l0 +l2 ) lipolysis rates were calculated by minimal model analysis. Body composition was determined by dual-energy x-ray absorptiometry. SAT leukocyte populations were characterized by flow cytometry analysis from biopsied samples obtained before and after the intervention. RESULTS: Colchicine treatment significantly decreased l2 and l0 +l2 versus placebo (p < 0.05). These changes were associated with a significant reduction in markers of systemic inflammation, including high-sensitivity C-reactive protein, resistin, and circulating monocytes and neutrophils (p < 0.01). Colchicine did not significantly alter SAT leukocyte population distributions (p > 0.05). CONCLUSIONS: In adults with obesity and MetS, colchicine appears to improve insulin regulation of lipolysis and reduce markers of systemic inflammation independent of an effect on local leukocyte distributions in SAT. Further studies are needed to better understand the mechanisms by which colchicine affects adipose tissue metabolic pathways in adults with obesity and MetS. Published 2021. This article is a U.S.Government work and is in the public domain in the USA.
OBJECTIVE: The aim of this study was to examine whether colchicine's anti-inflammatory effects would improve measures of lipolysis and distribution of leukocyte populations in subcutaneous adipose tissue (SAT). METHODS: A secondary analysis was conducted for a double-blind, randomized, placebo-controlled pilot study in which 40 adults with obesity and metabolic syndrome (MetS) were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. Non-insulin-suppressible (l0 ), insulin-suppressible (l2 ), and maximal (l0 +l2 ) lipolysis rates were calculated by minimal model analysis. Body composition was determined by dual-energy x-ray absorptiometry. SAT leukocyte populations were characterized by flow cytometry analysis from biopsied samples obtained before and after the intervention. RESULTS: Colchicine treatment significantly decreased l2 and l0 +l2 versus placebo (p < 0.05). These changes were associated with a significant reduction in markers of systemic inflammation, including high-sensitivity C-reactive protein, resistin, and circulating monocytes and neutrophils (p < 0.01). Colchicine did not significantly alter SAT leukocyte population distributions (p > 0.05). CONCLUSIONS: In adults with obesity and MetS, colchicine appears to improve insulin regulation of lipolysis and reduce markers of systemic inflammation independent of an effect on local leukocyte distributions in SAT. Further studies are needed to better understand the mechanisms by which colchicine affects adipose tissue metabolic pathways in adults with obesity and MetS. Published 2021. This article is a U.S.Government work and is in the public domain in the USA.
Authors: C M Steppan; S T Bailey; S Bhat; E J Brown; R R Banerjee; C M Wright; H R Patel; R S Ahima; M A Lazar Journal: Nature Date: 2001-01-18 Impact factor: 49.962
Authors: Stefan M Nidorf; Aernoud T L Fiolet; Arend Mosterd; John W Eikelboom; Astrid Schut; Tjerk S J Opstal; Salem H K The; Xiao-Fang Xu; Mark A Ireland; Timo Lenderink; Donald Latchem; Pieter Hoogslag; Anastazia Jerzewski; Peter Nierop; Alan Whelan; Randall Hendriks; Henk Swart; Jeroen Schaap; Aaf F M Kuijper; Maarten W J van Hessen; Pradyot Saklani; Isabel Tan; Angus G Thompson; Allison Morton; Chris Judkins; Willem A Bax; Maurits Dirksen; Marco Alings; Graeme J Hankey; Charley A Budgeon; Jan G P Tijssen; Jan H Cornel; Peter L Thompson Journal: N Engl J Med Date: 2020-08-31 Impact factor: 91.245
Authors: Nadine S Sauter; Fabienne T Schulthess; Ryan Galasso; Lawrence W Castellani; Kathrin Maedler Journal: Endocrinology Date: 2008-01-31 Impact factor: 4.736
Authors: Claudia Cavelti-Weder; Andrea Babians-Brunner; Cornelia Keller; Marc A Stahel; Malaika Kurz-Levin; Hany Zayed; Alan M Solinger; Thomas Mandrup-Poulsen; Charles A Dinarello; Marc Y Donath Journal: Diabetes Care Date: 2012-06-14 Impact factor: 19.112