Kupffer Cells Sense Free Fatty Acids and Regulate Hepatic Lipid Metabolism in High-Fat Diet and Inflammation
| Autor: | Iris Unterweger, Heike Weighardt, Irmgard Förster, Kira L Diehl, Kristina Hofmann, Christoph Thiele, Julia Vorac, Philippa Meiser, Lars Kuerschner |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Kupffer Cells Inflammation Fatty Acids Nonesterified Diet High-Fat Article Mice chemistry.chemical_compound Lipid droplet Internal medicine medicine Animals lcsh:QH301-705.5 nutrition/lipids chemistry.chemical_classification Fatty acid metabolism Tumor Necrosis Factor-alpha Chemistry lipids/chemistry non-alcoholic fatty liver disease Fatty acid Lipid metabolism General Medicine Lipid Metabolism metabolic disease medicine.disease Lipids Fatty Liver Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Endocrinology Liver lcsh:Biology (General) Hepatocyte Hepatocytes Click Chemistry Steatohepatitis medicine.symptom Steatosis |
| Zdroj: | Cells, Vol 9, Iss 2258, p 2258 (2020) Cells Volume 9 Issue 10 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells9102258 |
| Popis: | A high fat Western-style diet leads to hepatic steatosis that can progress to steatohepatitis and ultimately cirrhosis or liver cancer. The mechanism that leads to the development of steatosis upon nutritional overload is complex and only partially understood. Using click chemistry-based metabolic tracing and microscopy, we study the interaction between Kupffer cells and hepatocytes ex vivo. In the early phase of steatosis, hepatocytes alone do not display significant deviations in fatty acid metabolism. However, in co-cultures or supernatant transfer experiments, we show that tumor necrosis factor (TNF) secretion by Kupffer cells is necessary and sufficient to induce steatosis in hepatocytes, independent of the challenge of hepatocytes with elevated fatty acid levels. We further show that free fatty acid (FFA) or lipopolysaccharide are both able to trigger release of TNF from Kupffer cells. We conclude that Kupffer cells act as the primary sensor for both FFA overload and bacterial lipopolysaccharide, integrate these signals and transmit the information to the hepatocyte via TNF secretion. Hepatocytes react by alteration in lipid metabolism prominently leading to the accumulation of triacylglycerols (TAGs) in lipid droplets, a hallmark of steatosis. |
| Databáze: | OpenAIRE |
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