Grants and Contracts Details
Description
Over the last two decades, the prevalence of obesity has increased to epidemic proportion in US
general population. The rise in obesity portends a nation wild increase of type 2 diabetes and obesity related
chronic disease. Most importantly, gestational diabetes mellitus (GOM) increases neonate birth weight,
which closely associates with the development of adolescent and adult obesity. Therefore, the intrauterine
GOM environment predisposes high risk of obesity in GOM offspring. Our long-term goal is to investigate the
underlying mechanisms that increase birth weight and susceptibility of obesity of GOM offspring.
Adiponectin is an adipose-derived hormone and plays an important role in glucose and lipid
metabolism. Recent studies reveal that fetal and neonatal serum adiponectin concentrations are 4-7 folds
higher than adult and positively associate with gestation age and body weight, which indicates that
adiponectin may regulate fetal development and growth. Furthermore, most recent studies demonstrate that
overexpression adiponectin promotes obese phenotype in mice, and adiponectin enhances adipocyte
differentiation and lipid accumulation. Our preliminary studies demonstrate that newborn mice from mothers
with GOM exhibit high birth weight and elevated serum adiponectin protein levels. High fat feeding also
induces more weight gain in these GOM offspring. We hypothesize that GDM intrauterine environment
increases fetal adiponectin expression which predisposes high birth weight and susceptibility of
obesity in GDM offspring. In Specific Aim 1, we will determine the effect of GOM on fetal adiponectin gene
expression and circulating adiponectin protein profile using a well established GOM mouse model (db/+).
The relationship of maternal or fetal glucose and fat metabolism fetal adiponectin gene expression will be
evaluated. In Specific Aim 2, the role of adiponectin in GOM-associated high birth weight and development of
obesity will be studied by using adiponectin gene deficient mice. The results of this project, will not only test
the role of adiponectin in GOM-associated high birth weight and subsequent development of obesity, but
also provide very useful information regarding the role of adiponectin in fetal development and growth.
Status | Finished |
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Effective start/end date | 9/15/06 → 9/14/09 |
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