Placental Signaling Mechanisms Linking Maternal Obesity, High-Fat Diet, and Adiponectin Levels During Pregnancy to Fetal Overgrowth
Year: 2009
Type: article
Abstract: Placental Signaling Mechanisms Linking Maternal Obesity, High-Fat Diet, and Adiponectin Levels during Pregnancy to Fetal Overgrowth IntroductionIn pregnancies of obese women, increased expression of nutrient transport proteins in the placenta via unknown mechanisms may be leading to fetal overgrowth.Objective and Hypotheses The purpose of this research was to determine the effect of obesity, a high-fat diet, and adiponectin infusion on placental mTOR, STAT3, and AMP-K signaling and fetal growth.The following hypotheses were tested: (1) Placental mTOR and STAT3 signaling pathways are activated and AMP-K signaling is depressed in response to obesity and consumption of a high fat diet, thereby up-regulating placental nutrient transporters; (2) Adiponectin infusion activates placental AMP-K and inhibits mTOR signaling pathways and decreases fetal growth. Subjects and AnimalsHuman placental samples from obese (N=6) and lean (N=9) women who delivered at term, previously collected from a Swedish population and an American population, were used for analysis.Mice (C57/BL6) obtained from Jackson laboratory, were kept on standard lab chow or one of four diets (control, high-fat, high-sugar, high-fat/high-sugar) for 8 weeks prior to mating and throughout pregnancy, and studied close to term. MethodsThe activity of three key signaling pathways was determined by measuring expression of phosphorylated S6K (an indicator of mTOR activity), AMP-K, and STAT3 using western blot in placental homogenates of human and murine samples.Serum levels of adiponectin and leptin iv were measured in mouse maternal samples.Fetal growth at embryonic day 18.5 was recorded for all mouse samples. ResultsIn the Swedish cohort, a significant decrease in phosphorylated AMP-K expression (-30%, p<0.05) was observed in obese women giving birth to large babies.Mice on HF diet with large fetuses showed no significant changes in the expression of AMP-K, STAT3, or S6K.Mice who received adiponectin infusion had on average 36% (p<0.05)decreased phospho-S6K expression and 18% (p<0.05)smaller fetal weights versus controls.Serum levels of adiponectin and leptin were not significantly altered between groups of mice.Conclusion These preliminary data support the hypothesis that low maternal adiponectin and inhibition of placental AMP-K may contribute to fetal overgrowth in response to obesity/highfat diet by up-regulation of placental nutrient transporters.v vi
Author: Michael A. Schumacher
Institution: University of Cincinnati
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2597425505