Fetal Adiponectin Expression and Obesity of GDM Offspring

  • Shao, Jianhua (PI)

Grants and Contracts Details


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.
Effective start/end date9/15/069/14/09


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