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This suggests that, although animal experiments provide an excellent means of well-controlled functional analysis, firm data in humans are required before embarking upon such extensive and time-consuming experimental studies of human disease or biology. This study was supported by the German Federal Ministry of Education and Research (BmBF) through the Virtual Liver Project (FK0315763). ""We would like to respond to Brosch et?al.?regarding our manuscript ��Expression of the Splicing Factor Gene SFRS10 Is Reduced in Human Obesity and Contributes to Enhanced Lipogenesis�� ( Pihlajam?ki et?al., 2011b). Brosch performed RT-PCR in liver samples from 13 lean and 34 obese individuals, finding no differences in SFRS10 or LPIN1 expression. We wish to address points raised by Brosch, including GW-572016 in vitro experimental PTPRJ strategy and analysis of human SFRS10 expression. Our overall goal was to identify genes or pathways altered in key insulin-responsive tissues in obese humans with or without type 2 diabetes (T2D). Liver biopsies were obtained during elective surgery from individuals who also had glucose tolerance testing (to define undiagnosed T2D). With this approach, we achieved an initial cohort of 13 metabolically characterized individuals. Based on our prior observations (Patti et?al., 2003), we recognized we would have limited power to detect single differentially expressed genes with this sample size. For this reason, and because no single gene is likely responsible for complex disorders such as obesity and T2D, we planned pathway-based analysis, as described in human T2D expression studies (Patti et?al., 2003?and?Mootha et?al., 2003). Our manuscript details pathway analysis, pattern validation in mice, hypothesis development, and selection CP-868596 research buy of single genes for testing the hypothesis that splicing factors could contribute to metabolic phenotypes. A human liver array study with 13 samples has limited power to identify single differentially expressed genes. Few, if any, would ever be expected to reach the Bonferroni-corrected p value suggested by Brosch (p