EFFECTS OF PERFLUORINATED COMPOUNDS (PFCs) ON METABOLIC TISSUES AND THE BENEFITS OF CALORIC RESTRICTION

摘要: The CDC states that there has been a dramatic increase in obesity from 1990 to 2010. Type-II diabetes and prevalence are increasing worldwide. Often, concurrent, predispose individuals development of fatty liver disease, referred as Non-alcoholic disease (NAFLD). Perfluorooctane sulfonic acid (PFOS) perfluorooctanoic (PFOA) two commonly studied perfluorinated compounds (PFC’s) considered environmental toxicants have the potential elicit diabetic NAFLD phenotypes. This dissertation presents novel findings gaps within literature date. Traditionally, discussed regard with genetics, diet old age. Now, risk factors also need be chemicals. We found PFOS elicits an insulin-resistant phenotype adult mice, where they were not utilizing glucose readily compared controls. effect on therapeutic management interventions previously looked at. Here, we show interferes Metformin-induced decrease glucose. vast hepatic triglycerides exposure. In this thesis, was administered sub-chronic low dose (100μg/kg) daily mice fed ad libitum or placed caloric restriction (CR) for five weeks. cohort generated, observed exposure increased lipid content mature male dampened CR-induced lipids. administration did affect tolerance but interfere improvement tolerance. further associated suppression IRS-1 mRNA expression liver. As is closely tied insulin glucagon signaling production, it determined whether effects vivo due PFOSstimulated production. Using cultured mouse hepatocytes under conditions, evaluated could enhance glucagonstimulated stimulated hepatocyte production enhanced glucagon-induced Furthermore, HEPG2 cells, (25 250 μM) significantly output AiCar, which suppresses ineffective presence PFOS. These provide mechanistic explanation decreased our cohort. increases vitro models, even when challenged metformin well as, decreases utilization study suggesting glucagon-like effect. PFOA carboxylic environment. According EPA, levels widely distributed media (Houde et al., 2011; Gewertz 2013) blood general United States population. EPA known toxicant, carcinogen rodents. It detected human liver, kidney adipose tissue ranging 0.3 3.8ng/g highest concentrations (Maestri 2006). another study, obesogen mid-aged leptin altered at very concentration (Hines 2009). Potent activator peroxisomeproliferator activated receptor-alpha (Ppar-α) contributing oxidative stress activation oxidation pathways hepatocytes. Given its persistence, purpose evaluate treatment affects oxidation, synthesis, antioxidant response gene mice. Utilizing paradigm characterized by Environmental Protection Agency, treated 1.0 3.0 mg ammonium salt/kg 7 days. Adipose collected total RNA isolated. Analysis completed quantitative PCR. For most part, vehicleand PFOA-treated similar. Literature lacks data health, continue discovered. longer periods protein changes should examined.