OBJECTIVE: To investigate the role of low-grade inflammation and insulin resistance (HOMA2-IR) in adiposity-related increases in serum complement factor 3 (C3). Although C3 has been linked to type 2 diabetes and cardiovascular diseases, and C3 levels are closely related to body fat, the underlying mechanisms explaining this association are still unknown. METHODS: Adiposity measures (including BMI, waist circumference (WC), sagittal diameter and several skinfolds), HOMA2-IR and markers of inflammation (hs-CRP, IL-6, SAA, haptoglobin, ceruloplasmin, sICAM-1) were determined in 532 individuals (62% men, mean age 59±6.9 yrs) from the Cohort on Diabetes and Atherosclerosis Maastricht study. Markers of inflammation were standardized and compiled into an averaged inflammation score. Cross-sectional associations between adiposity measures and C3 and the mediating role of low-grade inflammation and/or HOMA2-IR herein were analysed with multiple linear regression models. RESULTS: Adiposity measurements were significantly associated with C3 levels, with the strongest (adjusted) associations found for WC (β=0.383; 95%CI 0.302-0.464) and sagittal diameter (β=0.412; 95%CI 0.333-0.490). Further adjustment for inflammation and HOMA2-IR attenuated these associations to β=0.115 (95%CI 0.030-0.200) and β=0.163 (95%CI 0.082-0.244) respectively. Multiple mediation analyses showed that inflammation [β=0.090 (95%CI 0.060-0.126)] and HOMA2-IR [β=0.179 (95%CI 0.128-0.236)] each explained, independently of one another, a significant portion of the association between WC and C3 (23% and 47%, respectively). Similar mediation by inflammation (19-27%) and HOMA2-IR (37-56%) was found for other adiposity measures. CONCLUSION: Systemic low-grade inflammation and insulin resistance may represent two independent pathways by which body fat leads to elevated C3 levels.
OBJECTIVE: To investigate the role of low-grade inflammation and insulin resistance (HOMA2-IR) in adiposity-related increases in serum complement factor 3 (C3). Although C3 has been linked to type 2 diabetes and cardiovascular diseases, and C3 levels are closely related to body fat, the underlying mechanisms explaining this association are still unknown. METHODS: Adiposity measures (including BMI, waist circumference (WC), sagittal diameter and several skinfolds), HOMA2-IR and markers of inflammation (hs-CRP, IL-6, SAA, haptoglobin, ceruloplasmin, sICAM-1) were determined in 532 individuals (62% men, mean age 59±6.9 yrs) from the Cohort on Diabetes and Atherosclerosis Maastricht study. Markers of inflammation were standardized and compiled into an averaged inflammation score. Cross-sectional associations between adiposity measures and C3 and the mediating role of low-grade inflammation and/or HOMA2-IR herein were analysed with multiple linear regression models. RESULTS: Adiposity measurements were significantly associated with C3 levels, with the strongest (adjusted) associations found for WC (β=0.383; 95%CI 0.302-0.464) and sagittal diameter (β=0.412; 95%CI 0.333-0.490). Further adjustment for inflammation and HOMA2-IR attenuated these associations to β=0.115 (95%CI 0.030-0.200) and β=0.163 (95%CI 0.082-0.244) respectively. Multiple mediation analyses showed that inflammation [β=0.090 (95%CI 0.060-0.126)] and HOMA2-IR [β=0.179 (95%CI 0.128-0.236)] each explained, independently of one another, a significant portion of the association between WC and C3 (23% and 47%, respectively). Similar mediation by inflammation (19-27%) and HOMA2-IR (37-56%) was found for other adiposity measures. CONCLUSION: Systemic low-grade inflammation and insulin resistance may represent two independent pathways by which body fat leads to elevated C3 levels.
Authors: Sonia I Vlaicu; Alexandru Tatomir; Dallas Boodhoo; Stefan Vesa; Petru A Mircea; Horea Rus Journal: Immunol Res Date: 2016-06 Impact factor: 2.829
Authors: Filip M Segers; Froukje J Verdam; Charlotte de Jonge; Bas Boonen; Ann Driessen; Ronit Shiri-Sverdlov; Nicole D Bouvy; Jan Willem M Greve; Wim A Buurman; Sander S Rensen Journal: PLoS One Date: 2014-10-09 Impact factor: 3.240
Authors: Julia Szendroedi; Aaruni Saxena; Katharina S Weber; Klaus Strassburger; Christian Herder; Volker Burkart; Bettina Nowotny; Andrea Icks; Oliver Kuss; Dan Ziegler; Hadi Al-Hasani; Karsten Müssig; Michael Roden Journal: Cardiovasc Diabetol Date: 2016-04-07 Impact factor: 9.951