Phenolic compounds from coffee by-products modulate adipogenesis-related inflammation, mitochondrial dysfunction, and insulin resistance in adipocytes, via insulin/PI3K/AKT signaling pathways

Food Chem Toxicol. 2019 Oct;132:110672. doi: 10.1016/j.fct.2019.110672. Epub 2019 Jul 12.


The aim of this study was to evaluate the inhibitory potential of aqueous extracts from coffee silverskin (CSE) and husk (CHE) and their main phenolics on adipogenesis, obesity-related inflammation, mitochondrial dysfunction, and insulin resistance, in vitro. Coffee by-products extracts (31-500 μg mL-1) and pure phenolics (100 μmol L-1) reduced lipid accumulation and increased mitochondrial activity in 3T3-L1 adipocytes. Also reduced the expression of inducible nitric oxide synthase and cyclooxygenase-2 and diminished secretion of pro-inflammatory factors in LPS-stimulated RAW2643.7 macrophages. Cytokine release diminished (tumor necrosis factor α: 23-57%; monocyte chemoattractant protein 1: 42-60%; interleukin-6: 30-39%) and adiponectin increased (7-13- fold) in adipocytes treated with macrophage-conditioned media. ROS scavenging and activation of peroxisome proliferator-activated receptor γ coactivator 1-α pathway counteracted mitochondrial dysfunction. Increases in insulin receptor (1.4 to 4-fold), phosphoinositide 3-kinase (2 to 3-fold) and protein kinase B (1.3 to 3-fold) phosphorylation, in conjunction with a decrease in serine phosphorylation of insulin receptor substrate 1, evoked glucose transporter 4 translocation (8-15-fold) and glucose uptake (44-85%). CSE and CHE phenolics inhibited adipogenesis and elicited adipocytes browning. Suppressing macrophages-adipocytes interaction alleviated inflammation-triggered mitochondrial dysfunction and insulin resistance. CSE and CHE are beneficial in reducing adipogenesis and inflammation-related disorders.

Keywords: Coffee by-products; Inflammation; Insulin resistance; Mitochondrial dysfunction; Phenolic compounds.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Coffee / chemistry*
  • Culture Media, Conditioned
  • Inflammation / pathology*
  • Insulin Resistance*
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / physiology
  • Phenols / isolation & purification
  • Phenols / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*


  • Coffee
  • Culture Media, Conditioned
  • Phenols
  • Reactive Oxygen Species
  • Proto-Oncogene Proteins c-akt