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

Molecules. 2016 Dec 15;21(12):1724. doi: 10.3390/molecules21121724.


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.

Keywords: adipocyte tissue; inflammation; insulin resistance; metabolic syndrome; obesity; obesity-related inflammation; riboflavin.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / immunology
  • Adipocytes / pathology*
  • Adiponectin / metabolism
  • Animals
  • Apoptosis / drug effects*
  • Cell Line
  • Cell Movement / drug effects
  • Chemokine CCL2 / metabolism
  • Coculture Techniques
  • Extracellular Matrix / metabolism
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Insulin Resistance / physiology
  • Interleukin-10 / metabolism
  • Lipopolysaccharides
  • Macrophages / cytology
  • Macrophages / immunology
  • Macrophages / pathology*
  • Matrix Metalloproteinase 9 / metabolism
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / prevention & control*
  • Mice
  • Obesity / pathology*
  • Riboflavin / pharmacology*


  • Adiponectin
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • IL10 protein, mouse
  • Lipopolysaccharides
  • Interleukin-10
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse
  • Riboflavin