Hepatic E4BP4 induction promotes lipid accumulation by suppressing AMPK signaling in response to chemical or diet- induced ER stress

Prolonged ER stress has been known to be one of the major drivers of impaired lipid homeostasis during the pathogenesis of non- alcoholic liver disease (NAFLD). However, the downstream mediators of ER stress pathway in promoting lipid accumulation remain poorly understood. Here, we present data showing the b- ZIP transcription factor E4BP4 in both the hepatocytes and the mouse liver is potently induced by the chemical ER stress inducer tunicamycin or by high- fat, low- methionine, and choline- deficient (HFLMCD) diet. We showed that such an induction is partially dependent on CHOP, a known mediator of ER stress and requires the E- box element of the E4bp4 promoter. Tunicamycin promotes the lipid droplet formation and alters lipid metabolic gene expression in primary mouse hepatocytes from E4bp4flox/flox but not E4bp4 liver- specific KO (E4bp4- LKO) mice. Compared with E4bp4flox/flox mice, E4bp4- LKO female mice exhibit reduced liver lipid accumulation and partially improved liver function after 10- week HFLMCD diet feeding. Mechanistically, we observed elevated AMPK activity and the AMPKβ1 abundance in the liver of E4bp4- LKO mice. We have evidence supporting that E4BP4 may suppress the AMPK activity via promoting the AMPKβ1 ubiquitination and degradation. Furthermore, acute depletion of the Ampkβ1 subunit restores lipid droplet formation in E4bp4- LKO primary mouse hepatocytes. Our study highlighted hepatic E4BP4 as a key factor linking ER stress and lipid accumulation in the liver. Targeting E4BP4 in the liver may be a novel therapeutic avenue for treating NAFLD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162728/3/fsb220918_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162728/2/fsb220918-sup-0001-FigS1-S10.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162728/1/fsb220918.pd

The site-specific primary calibration conditions for the Brewer spectrophotometer

The Brewer ozone spectrophotometer (the Brewer) is one of the World Meteorological Organization (WMO) Global Atmosphere Watch (GAW)’s standard ozone-monitoring instruments since the 1980s. The entire global Brewer ozone-monitoring network is operated and maintained via a hierarchical calibration chain, which started from world reference instruments that are independently calibrated via the primary calibration method (PCM) at a premium site (National Oceanic and Atmospheric Administration’s (NOAA) Mauna Loa Observatory, Hawaii). These world reference instruments have been maintained by Environment and Climate Change Canada (ECCC) in Toronto for the last 4 decades. Their calibration is transferred to the travelling standard instrument and then to network (field) Brewer instruments at their monitoring sites (all via the calibration transfer method; CTM)

Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly

For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae , that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type–related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution

Correction to: Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

International audienceIn this article, the name of the GLORIA-AF investigator Anastasios Kollias was given incorrectly as Athanasios Kollias in the Acknowledgements. The original article has been corrected