PATHWAY TO INSULIN RESISTANCE IN HUMANS: DISSECTING THE ROLE OF ETHNICITY, FAT DEPOTS AND INTERMEDIALRY METABOLITES

Abstract

This thesis examined the obesity-dependent and obesity-independent pathways of insulin resistance (IR). Ethnicity modifies the relationship between adiposity and IR. Study 1 showed that body fat partitioning does not explain ethnicity differences in IR. Study 2 to 4 are designed to examine nutrient (in particular branched-chain amino acids, BCAA) and nutrient handling in relation to IR. Study 2 showed that physical activities but not dietary protein intake has a mild influence on circulating BCAA. A sedentary lifestyle is associated with higher circulating BCAA only in males. Study 3 showed that within two weeks, changes in circulating BCAA are already pronounced (especially in postprandial period) after Roux-en-Y gastric bypass surgery but not with caloric restriction. Study 4 showed that short-term overfeeding is metabolically harmful. High-fat diet might favour fat storage and high-carbohydrate diet shows enhanced fatty acid oxidation with depletion of Kreb cycle substrates. Metabolic changes after high-fat-plus-BCAA diet are minimal.