Non alcoholic steatohepatitis dissertation

Short essay description
Diptadip Dattaroy , University of South Carolina. Due to the increased prevalence of obesity, non-alcoholic fatty liver disease NAFLD has become a major public health problem in the Western world and Asian countries. NAFLD includes a spectrum of histological characteristics ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis and can be characterized into to two major phenotypes: nonalcoholic fatty liver NAFL and nonalcoholic steatohepatitis NASH. Water disinfection byproducts like trihalomethanes can act as crucial risk factors for NAFLD progression. Here I have studied the molecular mechanisms of a water disinfection byproduct, Bromodichloromethane, in induction of hepatic inflammation and fibrogenesis. Similar effects of SsnB were also observed in cell culture model of kupffer cells.

Alcoholic and non-alcoholic steatohepatitis: global perspective and emerging science

Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches

Lindsey C. In this dissertation, I report the characterization of a new mouse model that recapitulates development of hepatocellular carcinoma HCC following spontaneous hepatic lipid accumulation, inflammation, and damage of liver tissue, due to complete loss of Trim24 expression. The hypothesis tested here was that TRIM24, the E3 ubiquitin ligase of p53, regulates genes that impact hepatic lipid inflammation and metabolism. In the first part of my dissertation, I establish through global gene expression, chromatin enrichment, biochemical, and immunohistochemical analyses that TRIM24 represses hepatic lipid accumulation, inflammation, and fibrosis and damage in the murine liver.

Nonalcoholic Fatty Liver Disease & NASH

Non-alcoholic fatty liver disease NAFLD is a spectrum of disturbances that includes simple steatosis, non-alcoholic steatohepatitis NASH , fibrosis, cirrhosis, and liver cancer. NAFLD affects individuals that consume the typical Western diet consisting of high levels of fats and carbohydrates. The increase in circulating free fatty acids, palmitate and oleate, or lipopolysaccharides LPS , induce oxidative stress and pro-inflammatory cytokine production in the liver, which all contribute to NAFLD progression. The treatment of sodium butyrate NaB or sodium propionate NaP was used to relieve oxidative stress and inflammation in liver cells. The expression of IL-8 in both models showed no significant differences in all treatments.
Significant changes in dietary habits have led to a rampant increase in metabolic disorders. Non-alcoholic fatty liver disease NAFLD is one such disorder characterized by the excess buildup of fat in hepatocytes of people who drink little or no alcohol. If not managed, NAFL simple steatosis progress into nonalcoholic steatohepatitis NASH and further deteriorate to cirrhosis leading to severe illness or even death.

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