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:PC9609-3952
External Project ID:NSC96-2628-B182-001-MY2
External Project ID:NSC96-2628-B182-001-MY2
Status | Finished |
---|---|
Effective start/end date | 01/08/07 → 31/07/08 |
Keywords
- mitochondria, reactive oxygen species, body fat, insulin resistance, diabetesmellitus
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.