Cereal Fiber Ameliorates High-Fat/Cholesterol-Diet-Induced Atherosclerosis by Modulating the NLRP3 Inflammasome Pathway in ApoE-/- Mice

J Agric Food Chem. 2018 May 16;66(19):4827-4834. doi: 10.1021/acs.jafc.8b00380. Epub 2018 May 7.

Abstract

Cereal fiber is associated with decreasing the risk of cardiovascular diseases. However, whether cereal fiber modulates inflammatory response and improves atherosclerosis remains unclear. This study evaluated the anti-atherosclerotic effect of cereal fibers from oat or wheat bran and explored the potential anti-inflammatory mechanisms. Male ApoE-/- mice were given a high-fat/cholesterol (HFC) diet or a HFC diet supplemented with 0.8% oat fiber or wheat bran fiber. After 18 weeks of the feeding period, serum lipids and inflammatory cytokines were measured. The relative protein levels of the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway and nuclear factor κB (NF-κB) were determined by the western blot method in aorta tissues. Pathologically, oat fiber and wheat fiber significantly reduced atherosclerotic plaques by 43.3 and 27.1%, respectively. Biochemically, cereal fiber markedly decreased the protein levels of myeloid differentiation factor 88 (MyD88) and toll-like receptor 4 (TLR4) in aortic tissues. The expression of NF-κB was similarly inhibited by both cereal fibers. In comparison to wheat bran fiber, oat fiber had greater effects in reducing the plague size and inhibiting TLR4/MyD88/NF-κB pathways. Such differences might come from modulation of the NLRP3 inflammasome pathway because the expressions of the cleavage of caspase-1 and interleukin (IL)-1β were inhibited only by oat fiber. The present study demonstrates that cereal fibers can attenuate inflammatory response and atherosclerosis in ApoE-/- mice. Such effects are pronounced with oat fiber and likely mediated by specific inhibition of oat fiber on the NLRP3 inflammasome pathway.

Keywords: NLRP3 inflammasome; atherosclerosis; cereal fiber; oat; wheat bran.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism*
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics*
  • Atherosclerosis / diet therapy*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Avena / chemistry
  • Avena / metabolism
  • Cholesterol / metabolism*
  • Diet, High-Fat / adverse effects*
  • Dietary Fiber / metabolism*
  • Humans
  • Inflammasomes / genetics
  • Inflammasomes / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Plant Extracts / metabolism
  • Signal Transduction
  • Triticum / chemistry
  • Triticum / metabolism

Substances

  • Anti-Inflammatory Agents
  • Apolipoproteins E
  • Dietary Fiber
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Plant Extracts
  • Cholesterol