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Ergosterol alleviates hepatic steatosis and insulin resistance via promoting fatty acid β-oxidation by activating mitochondrial ACSL1.
Cell Rep
January 2025
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China. Electronic address:
Sterols target sterol-sensing domain (SSD) proteins to lower cholesterol and circulating and hepatic triglyceride levels, but the mechanism remains unclear. In this study, we identify acyl-coenzyme A (CoA) synthetase long-chain family member 1 (ACSL1) as a direct target of ergosterol (ES). The C-terminal domain of ACSL1 undergoes conformational changes from closed to open, and ES may target the drug-binding pocket in the acetyl-CoA synthetase-like domain 1 (ASLD1) of ACSL1 to stabilize the closed conformation and maintain its activity.
View Article and Find Full Text PDFDeletion of AMP-activated protein kinase impairs metastasis and is rescued by ROS scavenging or ectopic CD36 expression.
Cell Rep
January 2025
Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA; Research and Development Section, Jesse Brown VA Medical Center, Chicago, IL 60612, USA. Electronic address:
AMPK's role in tumor initiation and progression is controversial. Here, we provide genetic evidence that AMPK is required for metastasis in mouse models of breast cancer. In a mouse model of spontaneous breast cancer metastasis, the deletion of AMPK before and after tumor onset decreased breast cancer metastasis, and similar results were obtained after AMPK deletion in breast cancer cell lines.
View Article and Find Full Text PDFAdvancing de novo lipogenesis: Genetic and metabolic insights.
Cell Metab
January 2025
Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. Electronic address:
De novo lipogenesis (DNL) is the process whereby cells synthesize fatty acids from acetyl-CoA, contributing to steatosis in fatty liver disease. Two new studies, using genetic mouse models, metabolomics, and pharmacology, identified alternative pathways in DNL and unexpected physiological effects when targeting key enzymes in this pathway.
View Article and Find Full Text PDFiTRAQ-based quantitative proteomic analysis of herbicide stress in Avena ludoviciana Durieu.
Sci Rep
January 2025
Iranian Research Institute of Plant Protection, Agricultural Research, Education and Extension Organization (AREEO), Tehran, Iran.
Winter wild oat (Avena sterilis subsp. ludoviciana (Durieu) Gillet & Magne) has been considered the most common and troublesome weed in wheat fields of Iran. The widespread and continuous use of herbicides has led to the emergence and development of resistant biotypes in A.
View Article and Find Full Text PDFPantothenate kinase 4 controls skeletal muscle substrate metabolism.
Nat Commun
January 2025
Department of Molecular Physiology of Exercise and Nutrition, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, Germany.
Article Synopsis
- Metabolic flexibility in skeletal muscle is crucial for healthy glucose and lipid metabolism, and its dysfunction can lead to metabolic diseases.
- Exercise improves metabolic flexibility and helps identify mechanisms that support metabolic health.
- The study reveals that pantothenate kinase 4 (PanK4) is vital for muscle metabolism, as its deletion disrupts fatty acid oxidation and elevates harmful acetyl-CoA levels, which lead to glucose intolerance, while increasing PanK4 enhances glucose uptake and lowers acetyl-CoA.
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