Effect of hepatocyte-specific PPARgamma knock out in the regulation of hepatic gene expression in mice fed a low fat diet or and high fat, cholesterol and fructose diet that induces NASH

In this study we sought to determine how hepatocyte-specific PPARgamma expression regulates hepatic gene expression in normal (healthy) mice fed a LFCF diet, or mice that were fed a HFCF diet for 24 weeks to induce non-alcoholic steatohepatitis (NASH). Specifically, we used chow-fed adult (10 week-old) PPARgamma floxed male mice and injected them with AAV8-TBG-Cre to knockout PPARgamma in hepatocytes (KO). A subset of PPARgamma floxed mice were injected with AAV8-TBG-Null to generate controls (C). Two weeks after AAV injections, half of the mice in each group were fed a low fat, cholesterol and fructose (LFCF) diet, or a high fat, cholesterol and fructose (HFCF) diet for 24 weeks. Livers were collected at the end of the study to assess hepatic gene expression with RNA-seq (performed by Novogen, Inc.) There are 4 groups: Group 1. LFCF-fed control mice: LF-C (4 samples: PG-413, PG-419, PG-437, PG-442). Group 2. LFCF-fed hepatocyte-specific PPARgamma knock out mice: LF-KO (4 samples: PG-412, PG-417, PG-436, PG-440). Group 3. HFCF-fed control mice: HF-C (5 samples: PG-399, PG-411, PG-398, PG-405, PG422). Group 4. HFCF-fed hepatocyte-specific PPARgamma knock out mice: HF-KO (6 samples: PG-396, PG-429, PG-425, PG-426, PG-427, PG-404). We have compared the gene expression levels between the following groups: - LF-C vs HF-C, and LF-KO vs HF-KO to assess the effect of HFCF-mediated NASH in the regulation of hepatic gene expression in control (C) and hepatocyte-specific PPARgamma knock out (KO) mice, respectively - LF-C vs LF-KO, and HF-C vs HF-KO to assess the effect of hepatocyte PPARgamma knock out in LFCF- and HFCF-fed mice respectively. Readcounts and FPKM of each sample are included in the processed files (comparisons indicated above), along with the Log2 fold change, p-value and p-adjusted.