Transgenerational Effects of Obesity
Description. A second area of research that my lab investigates is the impact of maternal phenotype (obesity/insulin resistance) and diet during pregnancy on the development of metabolic systems in offspring skeletal muscle and heart. Specifically, we have found derangements in mitochondrial oxidative capacity and insulin signaling in fetal and juvenile muscle form offspring exposed to an obesogenic fetal environment. Moving forward, we will be focusing efforts on identifying the cellular pathways and/or epigenetic profile that allows the persistence of the fetal phenotype and/or increased susceptibility to metabolic disease in juvenile offspring of obese pregnancy. We will also be testing the effectiveness of dietary and pharmaceutical interventions administered during pregnancy on ameliorating/preventing the metabolic and neurological reprogramming in fetal systems associated with high fat diet and obesity. This work is conducted in a nonhuman primate model in collaboration with the Oregon National Primate Research Center, Oregon Health Science University, University of Colorado Anschutz Medical Campus, Baylor University and Vanderbilt University and is supported through a NIH Team Science grant R24DK090964.
Tools & Skills. This work does not require handling of live animals. All tissue is collected by the pathologists during necropsy at ONPRC. Muscle samples are then process for the following types of studies.
- Mitochondrial respiration and substrate metabolism in fresh isolated fiber bundles
- Skeletal and cardiac fiber dissection
- High resolution respirometry
- Substrate metabolism
- Isolation of primary myoblasts for investigation/manipulation of cellular signaling pathways
- Primary muscle cell isolation & cell sorting by FACS
- Cell culture techniques & experiments
- Signaling Pathways by immunoblotting, immunoprecipiation, ChIP
- Gene Expression by qPCR
- Insulin Stimulate Glucose Uptake
- Metabolomics Analysis
- Epigenetic Analysis