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Article

Kupffer Cells Sense Free Fatty Acids and Regulate Hepatic Lipid Metabolism in High-Fat Diet and Inflammation

Life and Medical Science Institute (LIMES), University of Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany
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Cells 2020, 9(10), 2258; https://doi.org/10.3390/cells9102258
Received: 11 September 2020 / Revised: 3 October 2020 / Accepted: 6 October 2020 / Published: 8 October 2020
(This article belongs to the Special Issue Regulation of Lipid Metabolism in Health and Disease)
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. View Full-Text
Keywords: non-alcoholic fatty liver disease; nutrition/lipids; metabolic disease; lipids/chemistry non-alcoholic fatty liver disease; nutrition/lipids; metabolic disease; lipids/chemistry
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MDPI and ACS Style

Diehl, K.L.; Vorac, J.; Hofmann, K.; Meiser, P.; Unterweger, I.; Kuerschner, L.; Weighardt, H.; Förster, I.; Thiele, C. Kupffer Cells Sense Free Fatty Acids and Regulate Hepatic Lipid Metabolism in High-Fat Diet and Inflammation. Cells 2020, 9, 2258. https://doi.org/10.3390/cells9102258

AMA Style

Diehl KL, Vorac J, Hofmann K, Meiser P, Unterweger I, Kuerschner L, Weighardt H, Förster I, Thiele C. Kupffer Cells Sense Free Fatty Acids and Regulate Hepatic Lipid Metabolism in High-Fat Diet and Inflammation. Cells. 2020; 9(10):2258. https://doi.org/10.3390/cells9102258

Chicago/Turabian Style

Diehl, Kira L., Julia Vorac, Kristina Hofmann, Philippa Meiser, Iris Unterweger, Lars Kuerschner, Heike Weighardt, Irmgard Förster, and Christoph Thiele. 2020. "Kupffer Cells Sense Free Fatty Acids and Regulate Hepatic Lipid Metabolism in High-Fat Diet and Inflammation" Cells 9, no. 10: 2258. https://doi.org/10.3390/cells9102258

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