biostudies-literatureJiang BMajor Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education InstitutionsNational Natural Science Foundation of ChinaNatural Science Research of Jiangsu Higher Education Institutions of China101462https://www.ebi.ac.uk/biostudies/studies/S-EPMC8938331biostudies-literatureUnknown59<h4>Objective</h4>Chronic inflammatory response plays a prominent role in obesity-related nonalcoholic fatty liver disease (NAFLD). However, the intrahepatic triggering mechanism of inflammation remains obscure. This study aimed to elucidate the role of serum amyloid A1 (SAA1), an acute-phase response protein, in the obesity-induced hepatic inflammation and NAFLD.<h4>Methods</h4>Male mice were fed a high fat diet (HFD) for 16 weeks, and insulin resistance, hepatic steatosis, and inflammation in mice were monitored. Murine SAA1/2 was genetically manipulated to investigate the role of SAA1 in NAFLD.<h4>Results</h4>We found that SAA1 was increased in the NAFLD liver in both humans and mice. Knockout of SAA1/2 or knockdown of hepatic SAA1/2 promoted energy expenditure and alleviated HFD-induceMolecular metabolismSerum amyloid A1 exacerbates hepatic steatosis via TLR4-mediated NF-κB signaling pathway.PMC893833120KJA3100078183001118KJA310003818703718207045781770417820300128210043381670263Chen QHu YBen JWang DZhang HLi WYang XLi XJiang BZhu XYang QBai HLiu FfalseSerum amyloid A1 exacerbates hepatic steatosis via TLR4-mediated NF-κB signaling pathway.<h4>Objective</h4>Chronic inflammatory response plays a prominent role in obesity-related nonalcoholic fatty liver disease (NAFLD). However, the intrahepatic triggering mechanism of inflammation remains obscure. This study aimed to elucidate the role of serum amyloid A1 (SAA1), an acute-phase response protein, in the obesity-induced hepatic inflammation and NAFLD.<h4>Methods</h4>Male mice were fed a high fat diet (HFD) for 16 weeks, and insulin resistance, hepatic steatosis, and inflammation in mice were monitored. Murine SAA1/2 was genetically manipulated to investigate the role of SAA1 in NAFLD.<h4>Results</h4>We found that SAA1 was increased in the NAFLD liver in both humans and mice. Knockout of SAA1/2 or knockdown of hepatic SAA1/2 promoted energy expenditure and alleviated HFD-induce2022-01-01T00:00:00Z2022 May2025-04-04T08:53:28.589Z2025-04-04T08:53:28.589ZS-EPMC89383313524761110.1016/j.molmet.2022.101462