Dietary fats modulate neuroinflammation in mucin 2 knock out mice model of spontaneous colitis

Biochim Biophys Acta Mol Basis Dis. 2022 Mar 1;1868(3):166336. doi: 10.1016/j.bbadis.2021.166336. Epub 2021 Dec 29.

Abstract

Specific diets regulate neuroimmune responses and modify risk of inflammatory bowel diseases, including ulcerative colitis. A link between gut and brain inflammation is also emerging. We hypothesized that adjusting dietary fatty acid composition modulates the neuroimmune responses in the mucin 2 knock out mice model of spontaneous colitis. Mice were randomly divided into three groups and fed isocaloric diets that only differed in their fatty acid composition. Diets enriched with anhydrous milk fat, corn oil, or Mediterranean diet fats were used. After nine weeks, brain and serum concentrations of ten inflammatory cytokines were measured. Three of these cytokines, including interleukin (IL)-2, IL-12 p70 and interferon-γ, were differentially expressed in the brains of animals from the three diet groups while there were no differences in the serum concentrations of these cytokines. Since only limited information is available about the functions of IL-2 in the central nervous system, in vitro experiments were performed to assess its effects on microglia. IL-2 had no effect on the secretion of neurotoxins and nitric oxide by microglia-like cells, but it selectively regulated phagocytic activity and reactive oxygen species production by stimulated microglia-like cells. Modulation of microglial reactive oxygen species through altered brain IL-2 concentrations could be one of the mechanisms linking diets with modified risk of neuroimmune disorders including Parkinson's disease.

Keywords: Astrocytes; Brain cytokines; Dietary fatty acids; Gut-brain axis; Interleukin 2; Mediterranean diet; Microglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / complications*
  • Cytokines / metabolism*
  • Dietary Fats / adverse effects*
  • Fatty Acids / metabolism
  • Female
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia / metabolism
  • Microglia / pathology*
  • Mucin-2
  • Neuroinflammatory Diseases / etiology
  • Neuroinflammatory Diseases / metabolism
  • Neuroinflammatory Diseases / pathology*

Substances

  • Cytokines
  • Dietary Fats
  • Fatty Acids
  • Interleukin-2
  • Muc2 protein, mouse
  • Mucin-2
  • Interferon-gamma