Kors, Lotte and Rampanelli, Elena and Stokman, Geurt and Butter, Loes M. and Held, Ntsiki M. and Claessen, Nike and Larsen, Per W. B. and Verheij, Joanne and Zuurbier, Coert J. and Liebisch, Gerhard and Schmitz, Gerd and Girardin, Stephen E. and Florquin, Sandrine and Houtkooper, Riekelt H. and Leemans, Jaklien C. (2018) Deletion of NLRX1 increases fatty acid metabolism and prevents diet-induced hepatic steatosis and metabolic syndrome. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1864 (5). pp. 1883-1895. ISSN 0925-4439, 0006-3002
Full text not available from this repository. (Request a copy)Abstract
NOD-like receptor (NLR)X1 (NLRX1) is an ubiquitously expressed inflammasome-independent NLR that is uniquely localized in mitochondria with as yet unknown effects on metabolic diseases. Here, we report that NLRX1 is essential in regulating cellular metabolism in non-immune parenchymal hepatocytes by decreasing mitochondrial fatty acid-dependent oxidative phosphorylation (OXPHOS) and promoting glycolysis. NLRX1 loss in mice has a profound impact on the prevention of diet-induced metabolic syndrome parameters, non-alcoholic fatty liver disease (NAFLD) progression, and renal dysfunction. Despite enhanced caloric intake, NLRX1 deletion in mice fed a western diet (WD) results in protection from liver steatosis, hepatic fibrosis, obesity, insulin resistance, glycosuria and kidney dysfunction parameters independent from inflammation. While mitochondrial content was equal, NLRX1 loss in hepatocytes leads to increased fatty acid oxidation and decreased steatosis. In contrast, glycolysis was decreased in NLRX1-deficient cells versus controls. Thus, although first implicated in immune regulation, we show that NLRX1 function extends to the control of hepatocyte energy metabolism via the restriction of mitochondrial fatty acid-dependent OXPHOS and enhancement of glycolysis. As such NLRX1 may be an attractive novel therapeutic target for NAFLD and metabolic syndrome.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC KIDNEY-DISEASE; PATTERN-RECOGNITION RECEPTORS; NF-KAPPA-B; LIVER-DISEASE; INSULIN-RESISTANCE; NONALCOHOLIC STEATOHEPATITIS; CARDIOVASCULAR-DISEASE; SIGNALING PATHWAYS; LIPID-METABOLISM; INFLAMMATION; Innate immune receptor NLRX1; Metabolic syndrome; NAFLD; Metabolism; Fatty acid oxidation; Kidney disease |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Mar 2020 14:05 |
| Last Modified: | 09 Mar 2020 14:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14604 |
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