The pioneer factor hypothesis is not necessary to explain ectopic liver gene activation

The Pioneer Factor Hypothesis (PFH) states that pioneer factors (PFs) are a subclass of transcription factors (TFs) that bind to and open inaccessible sites and then recruit non-pioneer factors (nonPFs) that activate batteries of silent genes. The PFH predicts that ectopic gene activation requires the sequential activity of qualitatively different TFs. We tested the PFH by expressing the endodermal PF FOXA1 and nonPF HNF4A in K562 lymphoblast cells. While co-expression of FOXA1 and HNF4A activated a burst of endoderm-specific gene expression, we found no evidence for a functional distinction between these two TFs. When expressed independently, both TFs bound and opened inaccessible sites, activated endodermal genes, and 'pioneered' for each other, although FOXA1 required fewer copies of its motif for binding. A subset of targets required both TFs, but the predominant mode of action at these targets did not conform to the sequential activity predicted by the PFH. From these results we hypothesize an alternative to the PFH where 'pioneer activity' depends not on categorically different TFs but rather on the affinity of interaction between TF and DNA.

‘Away from home’ extra hepatic hepatocellular adenocarcinoma in gastric fundal submucosa

Patient presented with upper gastrointestinal bleeding which was scoped and diagnosed as bleeding gastrointestinal tumour intra procedure, subjected to laparotomy and wedge resection with unchanged postoperative diagnosis. Only later to find out the tissue was interpreted as metastases hepatoid adenocarcinoma without primary liver pathology. Thus likely point towards malignancy changes of undiagnosed ectopic liver tissue on gastric wall.

Insulin Resistance Shows Stronger Correlation With Ectopic Liver Fat Instead of Visceral Fat in Asian Indians

Introduction: Insulin resistance (IR) is associated with abdominal obesity. Asian Indians have higher insulin resistance at lower abdominal obesity levels as compared to the western population. However, the relative association of various compartments of abdominal fat, i.e., Subcutaneous Fat (SCAT), Visceral fat (VAT), and ectopic Liver Fat, is not very clear. Our study’s objective was to look for the association of abdominal fat composition in Asian Indians with IR level and gender and diabetes status. Methodology: Our study is an analytical cross-sectional study conducted from 2018–2020 at SMS Hospital located in northwest India. 91 subjects were studied during the study period and underwent MRI for SCAT, VAT, and Liver fat estimation. We divided subjects into tertile groups, based on HOMA-IR levels, and statistical analysis for SCAT, VAT, and Lipid fat in each tertile and as a whole group carried out. Similarly, we analysed data in male and female and diabetic and non-diabetic groups, as tertiles and as a whole. Results: Of the recruited subjects 49 were diabetics (M: F=23:26) and 42 were non-diabetic (M: F=12:30). In the overall group, HOMA-IR has a weak positive association with VAT and Liver Fat and a weak negative association with SCAT (R=0.28,0.38 and -0.11, respectively). From tertile1 to tertile3, there was a consistent increase in VAT and Liver fat (119.3, 121.1, 156.6 cm2 and 8.18, 10.02, 10.89% respectively), so that R value increases from -0.24 to 0.21 for VAT and -0.195 to 0.58 for Liver Fat. On the other hand, the SCAT levels were not different and correlation with IR declined from -0.299 to -0.39. On Sex wise analysis negative correlation of SCAT with IR become substantial from tertile1 to tertile3 in both males and females but strong correlation was seen in females (-0.189 to -0.515) though amount of SCAT was not different among tertiles. Both VAT and Liver Fat increased with tertile1 to terrtile3; IR was very strongly correlated with Liver Fat in both the sexes at higher tertiles (0.91 for males and 0.71 for females). In the diabetic group, liver fat was significantly associated with IR at higher tertile (R=0.9). The SCAT was negatively associated with IR, and a further decline in correlation coefficient with each tertile, became significant at 3rd tertile (-0.41) with a weak correlation of IR with VAT. These relations have similar SCAT and Liver fat trends but a strong correlation not seen in the non-diabetic group. Conclusion: Insulin resistance strongly correlated with ectopic liver fat in Asian Indians including diabetics with no gender disparity which became significant at higher tertile. As compared to ectopic liver fat, VAT has only a minor role in development of IR. SCAT has a protective role against IR in both diabetics and non-diabetics.