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

Diehl, Kira L; Vorac, Julia; Hofmann, Kristina; Meiser, Philippa; Unterweger, Iris A; Kuerschner, Lars; Weighardt, Heike; Thiele, Christoph

doi:10.3390/cells9102258

Cited by 38 publications

(46 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, Nakamoto et al used plain DHA (50 μL/day) [ 53 ], whereas in the present study, 4E% soybean oil was added to the FFC diet. Somewhat surprisingly, levels of plasma FFA were similar between groups, contrasting the findings of others in settings of diet-induced NAFLD in rodents [ 56 ]. However, in line with our findings, results of others also suggest that in the absence of abnormal weight gain and overweight, levels of FFA in plasma of mice fed a high-fat and high-sugar diet remain unchanged [ 57 ].…”

Section: Discussioncontrasting

confidence: 63%

Fortifying Butterfat with Soybean Oil Attenuates the Onset of Diet-Induced Non-Alcoholic Steatohepatitis and Glucose Intolerance

et al. 2021

View full text Add to dashboard Cite

The addition of plant oils such as soybean oil (S) to a diet rich in saturated fatty acids is discussed as a possible route to prevent or diminish the development of metabolic disease. Here, we assessed whether a butterfat-rich diet fortified with S affects the development of early non-alcoholic steatohepatitis (NASH) and glucose intolerance. Female C57BL/6J mice were fed a standard-control diet (C); a fat-, fructose-, and cholesterol-rich diet (FFC, 25E% butterfat, 50% (wt./wt.) fructose, 0.16% (wt./wt.) cholesterol); or FFC supplemented with S (FFC + S, 21E% butterfat + 4E% S) for 13 weeks. Indicators of liver damage, inflammation, intestinal barrier function, and glucose metabolism were measured. Lipopolysaccharide (LPS)-challenged J774A.1 cells were incubated with linolenic and linoleic acids (ratio 1:7.1, equivalent to S). The development of early NASH and glucose intolerance was significantly attenuated in FFC + S–fed mice compared to FFC-fed mice associated with lower hepatic toll-like receptor-4 mRNA expression, while markers of intestinal barrier function were significantly higher than in C-fed mice. Linolenic and linoleic acid significantly attenuated LPS-induced formation of reactive nitrogen species and interleukin-1 beta mRNA expression in J774A.1 cells. Our results indicate that fortifying butterfat with S may attenuate the development of NASH and glucose intolerance in mice.

show abstract

Section: Discussioncontrasting

confidence: 63%

Fortifying Butterfat with Soybean Oil Attenuates the Onset of Diet-Induced Non-Alcoholic Steatohepatitis and Glucose Intolerance

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Notably, apart from KCs being the main drivers of inflammation in NASH, they may also directly drive steatosis development, as KC depletion in rats has been shown to prevent HFD-induced steatosis [ 230 ]. In further support of this notion, in a HFD NAFLD model, LPS or FFA-driven activation of KCs mediated steatosis formation in hepatocytes via tumor necrosis factor signaling [ 231 ].…”

Section: Dysregulation Of Autophagy and Lipid Droplet Function In Non...mentioning

confidence: 99%

The ménage à trois of autophagy, lipid droplets and liver disease

et al. 2021

View full text Add to dashboard Cite

Autophagic pathways cross with lipid homeostasis and thus provide energy and essential building blocks that are indispensable for liver functions. Energy deficiencies are compensated by breaking down lipid droplets (LDs), intracellular organelles that store neutral lipids, in part by a selective type of autophagy, referred to as lipophagy. The process of lipophagy does not appear to be properly regulated in fatty liver diseases (FLDs), an important risk factor for the development of hepatocellular carcinomas (HCC). Here we provide an overview on our current knowledge of the biogenesis and functions of LDs, and the mechanisms underlying their lysosomal turnover by autophagic processes. This review also focuses on nonalcoholic steatohepatitis (NASH), a specific type of FLD characterized by steatosis, chronic inflammation and cell death. Particular attention is paid to the role of macroautophagy and macrolipophagy in relation to the parenchymal and non-parenchymal cells of the liver in NASH, as this disease has been associated with inappropriate lipophagy in various cell types of the liver.

show abstract

“…Various cell types are involved in the occurrence of AFL, such as hepatocytes, immune cells and HSCs. Among them, Kupffer cells was the most widely studied, which caused in ammation, liver damage and fatty liver by secreting a large number of in ammatory cytokines such as TNF-α, IL-1 and IL-17 [50]. In addition, it had also been found that HSCs not only played a role in the development of liver brosis by secreting extracellular matrix, but also promoted lipogenesis by secreting factors such as endocannabinoids.…”

Section: Discussionmentioning

confidence: 99%

MyD88 in Hepatic Stellate Cells Promotes the Development of Alcoholic Fatty Liver via the AKT Pathway

Wei

et al. 2021

Preprint

View full text Add to dashboard Cite

Myeloid differentiation primary response gene 88 (MyD88), an adaptor protein in the TLRs signaling pathway, is expressed in various liver cells including hepatocytes, Kupffer cells and hepatic stellate cells (HSCs). However, the specific role of MyD88 in HSCs in alcoholic fatty liver (AFL) has not been well investigated. Here, to study the role of MyD88 in HSCs in the development of AFL and its related molecular mechanism, chronic-binge ethanol mice models were established in mice with specific MyD88 knockout in quiescent (MyD88GFAP−KO) and activated HSCs (MyD88SMA−KO), respectively. The results showed that the expression of MyD88 in HSCs was significantly increased in ethanol-induced liver tissues of wild-type mice. MyD88 deficiency in quiescent HSCs inhibited inflammation and lipogenesis, but in activated HSCs it only inhibited inflammation under the ethanol feeding condition. Further mechanism studies found that MyD88 promoted the osteopontin (OPN) secretion of HSCs, which further activated the AKT signaling pathway of hepatocytes and upregulated lipogenic gene expression to promote fat accumulation. In addition, OPN also promotes inflammation by activating p-STAT1. Thus, MyD88 may represent a potential candidate target for the prevention and targeted therapy in AFL, and MyD88 inhibitor can be also applied in inhibiting adipogenesis.

show abstract

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

Cited by 38 publications

References 40 publications

Fortifying Butterfat with Soybean Oil Attenuates the Onset of Diet-Induced Non-Alcoholic Steatohepatitis and Glucose Intolerance

Fortifying Butterfat with Soybean Oil Attenuates the Onset of Diet-Induced Non-Alcoholic Steatohepatitis and Glucose Intolerance

The ménage à trois of autophagy, lipid droplets and liver disease

MyD88 in Hepatic Stellate Cells Promotes the Development of Alcoholic Fatty Liver via the AKT Pathway

Contact Info

Product

Resources

About