Aicda deficiency exacerbates high-fat diet-induced hyperinsulinemia but not gut dysbiosis in mice

Takeshi Tsuruta, Teresia Aluoch Muhomah, Kei Sonoyama, Qui D. Nguyen, Yurika Takase, Aoi Nishijima, Shiori Himoto, Emiko Katsumata, Naoki Nishino

Research output: Contribution to journalArticlepeer-review

Abstract

Immunoglobulin A (IgA) is a major antibody in the gut. We previously observed that a high-fat diet (HFD) reduces IgA reactivity to gut microbiota, but the physiological implications have yet to be elucidated. We hypothesized that a reduction of IgA reactivity to gut microbiota induced by a HFD may contribute to development of gut dysbiosis and inflammation that accompanies HFD feeding. To test our hypothesis, we used Aicda deficient mice, which have a deficiency in IgA production. Aicda deficient mice and wild-type mice were fed normal-fat diet or HFD for 12 weeks. We found that HFD feeding but not Aicda deficiency altered the fecal microbiota composition. Meanwhile, Aicda deficiency significantly increased gene expression of inflammatory cytokines in the ileum, but not in the colon despite no significant difference between diets. These results suggest that a reduction of IgA reactivity to gut microbiota induced by HFD partly contributes to development of inflammation in the ileum, but not to gut dysbiosis. We also found that the fasting blood insulin level was significantly increased by Aicda deficiency only under HFD feeding. Furthermore, the gene expression of monocyte chemoattractant protein1, a major chemokine responsible for the onset of hyperinsulinemia, in the liver was significantly increased by HFD feeding and tended to be increased by Aicda deficiency. These findings suggest that a reduction of IgA reactivity to gut microbiota induced by HFD contributes to hyperinsulinemia partly via increasing monocyte chemoattractant protein-1 expression in the liver.

Original languageEnglish
Pages (from-to)15-26
Number of pages12
JournalNutrition Research
Volume93
DOIs
Publication statusPublished - Sep 2021

Keywords

  • Gut microbiota
  • High fat diet
  • Hyperinsulinemia
  • IgA
  • Inflammation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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