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Obesity

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Inhibition Of Elongation Factor 1a-1 Activity And Hepatic Lipotoxicity, Alexandra Margaret Anne Hetherington Jun 2015

Inhibition Of Elongation Factor 1a-1 Activity And Hepatic Lipotoxicity, Alexandra Margaret Anne Hetherington

Electronic Thesis and Dissertation Repository

Elongation factor 1A-1 (eEF1A-1) was previously identified as a mediator of fatty acid-induced cell death (lipotoxicity) downstream of endoplasmic reticulum (ER) stress. Furthermore, inhibition of the peptide elongation activity of eEF1A-1 with the cyclic depsipeptide didemnin B (DB) diminishes ER stress and lipotoxicity in cultured hepatocytes. Since ER stress is involved in nonalcoholic fatty liver disease (NAFLD), it was hypothesized that administration of DB to obese mice with NAFLD would reduce hepatic lipotoxicity. Treatment with DB for one week improved several parameters associated with hepatic lipotoxicity and modestly decreased food intake without evidence of illness. Liver triglycerides and protein markers …


Fetal And Neonatal Exposure To Nicotine Augments Hepatic Fatty Acid Synthesis In Rat Offspring Long-Term, Noelle L. Ma Jun 2013

Fetal And Neonatal Exposure To Nicotine Augments Hepatic Fatty Acid Synthesis In Rat Offspring Long-Term, Noelle L. Ma

Electronic Thesis and Dissertation Repository

While nicotine replacement therapy (NRT) is presumed to be a safer alternative to smoking in pregnancy, the long-term consequences in offspring are still largely unknown. Animal studies now suggest that maternal nicotine exposure during pregnancy and lactation (MNE-PL) leads to a wide variety of adverse outcomes for the offspring, including increased adiposity. The focus of this study was to investigate how MNE-PL in rats may lead to liver dysfunction long-term in offspring through alterations in gene expression and epigenetic modifications. Postnatal day 180 (PND180) offspring exposed to nicotine during pregnancy and lactation (1mg/kg/day) exhibited increased circulating and hepatic triglycerides concomitant …