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Background & Aims: Hepatic insulin resistance is a fundamental phenomenon observed in both Type 2 diabetes (T2D) and metabolic (dysfunction) associated fatty liver disease (MAFLD). The relative contributions of nutrients, hyperinsulinemia, hormones, inflammation, and other cues are difficult to parse as they are convoluted by interplay between the local and systemic events. Here, we used a well-established human liver microphysiological system (MPS) to establish a physiologically-relevant insulin-responsive metabolic baseline and probe how primary human hepatocytes respond to controlled perturbations in insulin, glucose, and free fatty acids (FFAs).
View Article and Find Full Text PDFThe multifaceted roles of macrophages in the transition from hepatitis to hepatocellular carcinoma: From mechanisms to therapeutic strategies.
Biochim Biophys Acta Mol Basis Dis
January 2025
Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, PR China. Electronic address:
Macrophages are central to the progression from hepatitis to hepatocellular carcinoma (HCC), with their remarkable plasticity and ability to adapt to the changing liver microenvironment. Chronic inflammation, fibrosis, and ultimately tumorigenesis are driven by macrophage activation, making them key regulators of liver disease progression. This review explores the diverse roles of macrophages in the transition from hepatitis to HCC.
View Article and Find Full Text PDFThe histamine pathway is a target to treat hepatic experimental erythropoietic protoporphyria.
Cell Mol Gastroenterol Hepatol
January 2025
Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ, USA. Electronic address:
Background & Aims: Erythropoietic protoporphyria (EPP) is caused by mutations in ferrochelatase which inserts iron into protoporphyrin-IX (PP-IX) to generate heme. EPP is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. Despite available drugs that address photosensitivity, treatment of EPP-related liver disease remains an unmet need.
View Article and Find Full Text PDFPellino 3 E3 ligase promotes starvation-induced autophagy to prevent hepatic steatosis.
Sci Adv
January 2025
Cellular Homeostasis and Recycling, Danish Cancer Institute, DK-2100 Copenhagen, Denmark.
Nutrient deprivation is a major trigger of autophagy, a conserved quality control and recycling process essential for cellular and tissue homeostasis. In a high-content image-based screen of the human ubiquitome, we here identify the E3 ligase Pellino 3 (PELI3) as a crucial regulator of starvation-induced autophagy. Mechanistically, PELI3 localizes to autophagic membranes, where it interacts with the ATG8 proteins through an LC3-interacting region (LIR).
View Article and Find Full Text PDFViability Assessment During Normothermic Machine Liver Perfusion: A Literature Review.
Liver Int
February 2025
Department of Hepatobiliary and Digestive Surgery, University Hospital, Rennes 1 University, Rennes, France.
The discrepancy between donor organ availability and demand leads to a significant waiting-list dropout rate and mortality. Although quantitative tools such as the Donor Risk Index (DRI) help assess organ suitability, many potentially viable organs are still discarded due to the lack of universally accepted markers to predict post-transplant outcomes. Normothermic machine perfusion (NMP) offers a platform to assess viability before transplantation.
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