Studies of Genetic and Nutritional Factors in Disorders of Glucose and Lipid Metabolism

(JSNFS Award for Excellence in Research (2018))

Abstract

We have tried to isolate the causative genes for type 2 diabetes and fatty liver, and investigated food factors that can prevent disorders of glucose and lipid metabolism. Firstly, in mouse SMXA-recombinant inbred strains, we demonstrated that SMXA5 mice showed hyperglycemia, glucose intolerance and fatty liver, which were worsened by a high-fat diet. Quantitative trait locus (QTL) analysis using SMXA5 mice fed a high-fat diet showed that the diabetes locus was located on chromosome 2 and the fatty liver locus on chromosome 12. Congenic mouse strains harboring the diabetes or fatty liver locus were obtained and analyzed, and then we selected four candidate genes for diabetes and one candidate gene for fatty liver. Secondly, we investigated several food factors that could prevent diabetes and obesity. Coffee ingestion prevented the development of insulin resistance and hyperglycemia in a mouse model of type 2 diabetes with insulin resistance, and also suppressed the development of type 1 diabetes in streptozotocin-treated mice. These results have revealed a novel mechanism for development of diabetes and fatty liver, and may contribute to the dietary prevention of these disorders.