The Role of Mitochondria in Pathogenesis of Chronic Inflammation and Insulin Resistance Related to Altered Body Fat Distribution

  • Wang, Pei-Wen (PI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

The future impact of a diabetes-pandemic on health care resources in Asian countries is potentially catastrophic. Diabetes and all traits of metabolic syndrome (MtS) are risk factors for cardiovascular diseases (CVD). Although the original conceptualization of this syndrome was based on insulin resistance (IR), the pathogenesis has been unclear. Accumulating evidence suggest that deranged adipocyte metabolism and altered body fat distribution are important determinants of IR. Recent understanding of the molecular events linking excessive fat to IR has focused on the oxidative stress and chronic inflammation in accumulated adipose tissue. Central fat excess is known to be associated with an increase in serum inflammatory markers and IR. Furthermore, reactive oxygen species (ROS) overproduction by mitochondria has been proposed to cause the onset and progression of diabetes and its complications. This two-year study is designed to investigate the role and the changes of mitochondria in altered body fat distribution, IR and diabetes development. In the 1st year: Comparison of mitochondrial DNA (mtDNA) copy number, level of oxidative stress and intracellular antioxidants capacity in peripheral blood cells of individuals with normal and altered body fat distribution will be conducted. Blood tests for plasma sugar, inflammation makers, IR index and body fat measurement by computed-topography (CT), categorized into intra-peritoneal, retro-peritoneal and subcutaneous three distinct fat compartments, will be performed. Comparison between individuals with same body mass index (BMI) but different body fat distribution will be conducted. At the end of the 2-year study, the volunteers will be followed up for plasma sugar and IR index again. Mitochondrial study will be conducted in cases with significant changes of glucose dysregulation. In the 2nd year: Using C57BL/6J mice fed with high fat diet (diet-induced obesity model), blood tests for plasma sugar, inflammation makers, IR index and body fat measurement by micro-CT, categorized into visceral, liver, and subcutaneous fat, will be checked. Comparison of mtDNA content, number and function, level of oxidative stress and antioxidants capacity in adipocytes from visceral and subcutaneous fat will be conducted during both early and late phase of the development of obesity and diabetes. This project will elucidate the possible differences of mitochondrial biogenesis in individuals with same BMI but different body fat distribution. Furthermore, using the animal model of diet-induced obesity, we can compare the mitochondrial mass and function in adipocytes from different body sites during the course of development of diabetes. In this way, the association and a possible causal relationship between mitochondria, IR, and deranged fat metabolism can be understood.

Project IDs

Project ID:PC9706-0784
External Project ID:NSC96-2628-B182-001-MY2
StatusFinished
Effective start/end date01/08/0831/07/09

Keywords

  • mitochondria
  • reactive oxygen species
  • body fat
  • insulin resistance

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