Interlukin-17 is produced in the gut in response to dietary fats and regulates insulin secretion

Author(s)

Carina Solon Silva

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2015-03-03

Examining board members

Licio Augusto Velloso; Adriana Souza Torsoni; Antonio Carlos Boschero; Silvana Bordin; Luciana Chagas Caperuto

• Advisor: Licio Augusto Velloso

Abstract

Interleukin-17 (IL17) is involved in the immune response against intestinal pathogens, and its anomalous expression in the gut can occur in conditions such as type 1 diabetes (T1D) 1, autoimmune encephalomyelitis 2 and Crohn¿sdisease 3. Because dietary factors can change the gut microbiota, impacting metabolic diseases 4, we hypothesized that IL17 could be directly modulated by nutrients and might play a role in obesity and type 2 diabetes (T2D). Here, we show that dietary fats induced IL17 expression, predominantly in the ileum. Both in vivo and in isolated pancreatic islets, IL17 stimulated insulin secretion, while its systemic inhibition resulted in glucose intolerance. Mice KO for the main IL17 receptor (IL17RA) were glucose intolerant due to anomalous embryonic development of the pancreatic islets, which were smaller and were depleted of insulin-producing cells. In humans, blood IL17 increased following a meal. This increase was significantly higher in obese normoglycemic individuals than in obese subjects with diabetes. Similar to those of rodents, human islets were also stimulated to secrete insulin in the presence of IL17. Thus, we identified IL17 as a gut sensor of dietary fats, which exerted an incretin-like effect. In addition, the presence IL17RA was important for normal development of the pancreatic islets (AU)