HTC-15 - Abstract

Abstract Title: Hyphenated Techniques for comprehensive analysis of metabolites in biological systems to describe metabolic changes caused by disease, environmental, nutritional, or genetic factors
Abstract Type: Seminar
Presenter Name: Prof Tuulia Hyötyläinen
Company/Organisation: Örebro University
Session Choice: Advanced Analysis of Food and Beverages

Abstract Information :

A major health care challenge is to understand the relationships and interactions between genetic variations and various environmental triggers of disease. The proportion of chronic disease explained by genetic variation is ca. 10-20 % while the rest is explained by various environmental factors, such as diet, lifestyle, gut microbial activity and exposure to environmental contaminants. Currently, it has been suggested that the exposure to toxic environmental chemicals, for example, exposome plays an important role for e.g. in the development of type 2 diabetes, autoimmune diseases, obesity, and in neurological diseases. Furthermore, recent findings have implicated that toxic exposure together with e.g. unhealthy diet may have a strong synergic effect on the disease development and progression. In health research, it is highly challenging to study the interplay of these various factors and for that, metabolomics combined with exposure studies, by utilization of comprehensive chemical characterization for both metabolites as well as environmental pollutants, is a very promising tool.

In our studies, we have been investigating the factors and metabolic pathways in non-alcoholic fatty liver disease (NAFLD), diabetes as well as in autoimmune diseases. By combining studies and data on metabolomics in both blood-based samples and tissues, exposure data, clinical variables, gut microbiota composition, genetics and transcriptomics, intervention studies as well as results from animal models, we have been able to gain novel insights of the factors leading to NAFLD and linked with the development of insulin resistance. Although NAFLD commonly coexists with obesity, insulin resistance and type 2 diabetes, common genetic variants have also shown to be associated with NAFLD. Interestingly, however, steatosis in patatin-like phospholipase domain-containing 3 (PNPLA3) associated NAFLD is not accompanied by features of metabolic syndrome while the MBOAT7 variant rs641738 increases severity of non-alcoholic fatty liver disease in humans. By using comprehensive metabolic characterization, we have been able to identify circulating metabolic markers that can not only predict the NAFLD but also differentiate the patients with the metabolic and the genotypic NAFLD. The differences are associated particularly with changes in lipid metabolism. We have also, by using genome-scale study, showed that the disease is related to reduced metabolic adaptability. Moreover, our studies indicate that the type of diet has a significant impact on the disease progression, and that exposure to environmental pollutants is associated with both the development of insulin resistance as well as the non-alcoholic fatty liver disease.