Dietary wheat amylase trypsin inhibitors promote features of murine non-alcoholic fatty liver disease

Sci Rep. 2019 Nov 25;9(1):17463. doi: 10.1038/s41598-019-53323-x.

Abstract

We previously demonstrated that a common dietary protein component, wheat amylase trypsin inhibitors (ATI), stimulate intestinal macrophages and dendritic cells via toll like receptor 4. Activation of these intestinal myeloid cells elicits an inflammatory signal that is propagated to mesenteric lymph nodes, and that can facilitate extraintestinal inflammation. Mice were fed a well-defined high fat diet, with (HFD/ATI) or without (HFD) nutritionally irrelevant amounts of ATI. Mice on HFD/ATI developed only mild signs of intestinal inflammation and myeloid cell activation but displayed significantly higher serum triglycerides and transaminases compared to mice on HFD alone. Moreover, they showed increased visceral and liver fat, and a higher insulin resistance. ATI feeding promoted liver and adipose tissue inflammation, with M1-type macrophage polarization and infiltration, and enhanced liver fibrogenesis. Gluten, the major protein component of wheat, did not induce these pathologies. Therefore, wheat ATI ingestion in minute quantities comparable to human daily wheat consumption exacerbated features of the metabolic syndrome and non-alcoholic steatohepatitis, despite its irrelevant caloric value.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animal Feed / toxicity
  • Animals
  • Collagen / analysis
  • Diet, Fat-Restricted
  • Diet, High-Fat / adverse effects
  • Gene Expression Profiling
  • Glucose Tolerance Test
  • Glutens / administration & dosage
  • Glutens / toxicity
  • Hypertriglyceridemia / etiology
  • Inflammation
  • Insulin / blood
  • Insulin Resistance
  • Intra-Abdominal Fat / pathology
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / pathology
  • Male
  • Metabolic Syndrome / complications
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / etiology*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Triticum / chemistry*
  • Trypsin Inhibitors / adverse effects*
  • Zein / administration & dosage

Substances

  • Insulin
  • Trypsin Inhibitors
  • Glutens
  • Collagen
  • Zein
  • Alanine Transaminase