TY  - JOUR
AU  - Item, F
AU  - Wueest, S
AU  - Lemos, V
AU  - Stein, S
AU  - Lucchini, FC
AU  - Denzler, R
AU  - Fisser, MC
AU  - Challa, TD
AU  - Pirinen, E
AU  - Kim, Y
AU  - Hemmi, S
AU  - Gulbins, E
AU  - Gross, A
AU  - O'Reilly, LA
AU  - Stoffel, M
AU  - Auwerx, J
AU  - Konrad, D
Y2  - 2020/12/21
Y1  - 2017/09/07
SN  - 2041-1723
UR  - http://hdl.handle.net/11343/257151
AB  - Nonalcoholic fatty liver disease is one of the most prevalent metabolic disorders and it tightly associates with obesity, type 2 diabetes, and cardiovascular disease. Reduced mitochondrial lipid oxidation contributes to hepatic fatty acid accumulation. Here, we show that the Fas cell surface death receptor (Fas/CD95/Apo-1) regulates hepatic mitochondrial metabolism. Hepatic Fas overexpression in chow-fed mice compromises fatty acid oxidation, mitochondrial respiration, and the abundance of mitochondrial respiratory complexes promoting hepatic lipid accumulation and insulin resistance. In line, hepatocyte-specific ablation of Fas improves mitochondrial function and ameliorates high-fat-diet-induced hepatic steatosis, glucose tolerance, and insulin resistance. Mechanistically, Fas impairs fatty acid oxidation via the BH3 interacting-domain death agonist (BID). Mice with genetic or pharmacological inhibition of BID are protected from Fas-mediated impairment of mitochondrial oxidation and hepatic steatosis. We suggest Fas as a potential novel therapeutic target to treat obesity-associated fatty liver and insulin resistance.Hepatic steatosis is a common disease closely associated with metabolic syndrome and insulin resistance. Here Item et al. show that Fas, a member of the TNF receptor superfamily, contributes to mitochondrial dysfunction, steatosis development, and insulin resistance under high fat diet.
LA  - English
PB  - NATURE PUBLISHING GROUP
T1  - Fas cell surface death receptor controls hepatic lipid metabolism by regulating mitochondrial function
DO  - 10.1038/s41467-017-00566-9
IS  - Nature Communications
VL  - 8
IS  - 1
L1  - /bitstream/handle/11343/257151/PMC5589858.pdf?sequence=1&isAllowed=y
ER  -