Cell metabolism, 2012-07, Vol.16 (1), p.44-54
2012
Details
- Autor(en) / Beteiligte
- Titel
- Hyperresponsivity to Low-Dose Endotoxin during Progression to Nonalcoholic Steatohepatitis Is Regulated by Leptin-Mediated Signaling
- Ist Teil von
- Cell metabolism, 2012-07, Vol.16 (1), p.44-54
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Although bacterial endotoxin, such as lipopolysaccharide (LPS), plays a key role in the pathogenesis of nonalcoholic steatohepatitis (NASH), detailed mechanisms of this pathogenesis remain unclear. Here, we demonstrate that upregulation of CD14 by leptin-mediated signaling is critical to hyperreactivity against endotoxin during NASH progression. Upregulation of CD14 in Kupffer cells and hyperreactivity against low-dose LPS were observed in high-fat diet (HFD)-induced steatosis mice, but not chow-fed-control mice. Hyperresponsivity against low-dose LPS led to accelerated NASH progression, including liver inflammation and fibrosis. Administering leptin in chow-fed mice caused increased hepatic expression of CD14 via STAT3 signaling, resulting in hyperreactivity against low-dose LPS without steatosis. In contrast, a marked decrease in hepatic CD14 expression was observed in leptin-deficient ob/ob mice, despite severe steatosis. Our results indicate that obesity-induced leptin plays a crucial role in NASH progression via enhanced responsivity to endotoxin, and we propose a mechanism of bacteria-mediated progression of NASH. [Display omitted] ► HFD-induced steatosis in mice promotes hyperresponsivity to low-dose LPS► CD14-positive Kupffer cells induced by feeding HFD regulate responsivity to LPS ► Leptin regulates CD14 expression in Kupffer cells via STAT3 signaling ► Leptin plays a critical role in NASH via control of responsivity to endotoxin
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1550-4131eISSN: 1932-7420DOI: 10.1016/j.cmet.2012.05.012Titel-ID: cdi_proquest_miscellaneous_1024350233
- Format
- –
- Schlagworte
- Alanine Transaminase - blood, Animals, Cell Line, Cytokines - blood, Cytokines - genetics, Cytokines - metabolism, Diet, High-Fat - adverse effects, Fatty Liver - etiology, Fatty Liver - immunology, Fatty Liver - metabolism, Fatty Liver - pathology, Gene Expression, Hepatitis, Animal - etiology, Hepatitis, Animal - immunology, Hepatitis, Animal - metabolism, Hepatitis, Animal - pathology, Humans, Leptin - metabolism, Leptin - physiology, Lipopolysaccharide Receptors - genetics, Lipopolysaccharide Receptors - metabolism, Lipopolysaccharides - pharmacology, Liver Cirrhosis, Liver Cirrhosis, Experimental - etiology, Liver Cirrhosis, Experimental - immunology, Liver Cirrhosis, Experimental - metabolism, Liver Cirrhosis, Experimental - pathology, Male, Mice, Mice, Inbred C57BL, Mice, Obese, Non-alcoholic Fatty Liver Disease, Signal Transduction, STAT3 Transcription Factor - metabolism, Toll-Like Receptor 4 - genetics, Toll-Like Receptor 4 - metabolism, Tumor Necrosis Factor-alpha - metabolism