Moreover, many arguments suggest that obese patients with NAFLD also develop hepatic leptin resistance. However, the molecular mechanisms that lead to liver leptin resistance have yet to be described. The main objective of this study is to analyze the relation between NAFLD progression during morbid obesity and the expression level of genes related to hepatic leptin and insulin signaling. Method http://www.selleckchem.com/screening/tyrosine-kinase-inhibitor-library.html Patient cohort included 87 morbidly obese subjects who underwent bariatric surgery. Liver biopsies were obtained at the moment of surgery. NAFLD was diagnosed by anatomopathological evaluation of liver biopsies using the Kleiner score. Hepatic gene expression level was estimated by measuring mRNA concentration using a methodology

based on Real Time PCR (including normalization of mRNA concentration by three housekeeping genes). Seven expression levels were analyzed: long and short leptin receptor isoforms (OB-Rb and OB-Ra), insulin receptor (INS-R), ISR-1,IRS-2 (Insulin Receptor Substrate 1 and 2), SOCS-1 and SOCS-3 (Suppressor of

Cytokine Signaling 1 and 3). Results The patients were classified into three groups: 10 without NAFLD (group 1); 33 with liver steatosis but without steatohepatitis (group 2, Kleiner score<3) and 44 with probable or confirmed steatohepatitis (group 3, Kleiner score≥3). Comparison of the average gene expression levels in obese patients without NAFLD (group 1) and in those with NAFLD (groups 2 and 3) revealed a non-significant tendency toward a decrease in leptin and insulin receptors, IRS-1 and SOCS-3 (p<0.1), and a non-significant tendency toward an increase in SOCS-1 ABT-263 (p<0.1). Moreover, the patients without NAFLD presented a marked degree of correlation between the expression

of leptin and insulin signaling-related genes (above 0.8 in all combinations and a maximum of 0.986 for both leptin receptor isoforms). Interestingly, all these genetic correlation levels decreased or disappeared as NAFLD progressed. Conclusions In morbidly obese patients without NAFLD, high levels of correlation between leptin and insulin signaling-related genes suggest MCE公司 that hepatic leptin and insulin signaling pathways share key expression factors. Moreover, the reduction in these correlations as NAFLD progresses suggests that liver endocrine homeostasis is affected by NAFLD development. This study presents new perspectives on the mechanism that gives rise to leptin and insulin hepatic resistance during NAFLD origin and progression. Disclosures: The following people have nothing to disclose: Angel Carazo, Laura Sanjuan, Luis Miguel Alcázar, Trinidad Caballero, Ana Gila, Jose Antonio Muñoz-Gámez, Jesus Garcia-Rubio, Antonio Cozar, Manuel De la Mata, Paloma Muñoz-de-Rueda, Javier Salmeron Background & Aims: Non-alcoholic Fatty Liver Diseases (NAFLD), especially its critical stage of non-alcoholic steatohepatitis (NASH), has become one of the most important public health issues worldwide.