title: Riboflavin Reduces Pro-Inflammatory Activation of Adipocyte-Macrophage Co-culture. Potential Application of Vitamin B2 Enrichment for Attenuation of Insulin Resistance and Metabolic Syndrome Development.
abstract: Due to the progressive increase in the incidence of obese and overweight individuals, cardiometabolic syndrome has become a worldwide pandemic in recent years. Given the immunomodulatory properties of riboflavin, the current study was performed to investigate the potency of riboflavin in reducing obesity-related inflammation, which is the main cause of insulin resistance, diabetes mellitus 2 or arteriosclerosis. We determined whether pretreatment with a low dose of riboflavin (10.4-1000 nM) affected the pro-inflammatory activity of adipocyte-macrophage co-culture (3T3 L1-RAW 264.7) following lipopolysaccharide stimulation (LPS; 100 ng/mL) which mimics obesity-related inflammation. The apoptosis of adipocytes and macrophages as well as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1beta (IL-1β), monocyte chemotactic protein 1 (MCP-1), high-mobility group box 1 (HMGB1), transforming growth factor-beta 1 (TGFβ), interleukin 10 (IL-10), inducible nitric oxide synthase (iNOS), nitric oxide (NO), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1) expression and release, macrophage migration and adipokines (adiponectin and leptin) were determined. Our results indicated an efficient reduction in pro-inflammatory factors (TNFα, IL-6, MCP-1, HMGB1) upon culture with riboflavin supplementation (500-1000 nM), accompanied by elevation in anti-inflammatory adiponectin and IL-10. Moreover, macrophage migration was reduced by the attenuation of chemotactic MCP-1 release and degradation of the extracellular matrix by MMP-9. In conclusion, riboflavin effectively inhibits the pro-inflammatory activity of adipocyte and macrophage co-cultures, and therefore we can assume that its supplementation may reduce the likelihood of conditions associated with the mild inflammation linked to obesity.
authors.affiliation: Department of Ergonomics and Exercise Physiology, Faculty of Health Science, Jagiellonian University Medical College, Grzegorzecka 20, 31-531 Krakow, Poland. agnieszka.mazur@uj.edu.pl.
authors.forename: Agnieszka Irena
authors.initials: AI
authors.lastname: Mazur-Bialy
authors.affiliation: Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland. ewa.pochec@uj.edu.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Pocheć
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D018920:Coculture Techniques; D005109:Extracellular Matrix / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D007333:Insulin Resistance / Q000502:physiology; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000517:prevention & control*; D051379:Mice; D009765:Obesity / Q000473:pathology*; D012256:Riboflavin / Q000494:pharmacology*
chemical_list: D052242:Adiponectin; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D016753:Interleukin-10; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D012256:Riboflavin
keywords: adipocyte tissue; inflammation; insulin resistance; metabolic syndrome; obesity; obesity-related inflammation; riboflavin