skeletal muscle pgc-1α is required for maintaining an acute lps-induced tnfα response骨骼肌pgc-1α需要维护一个急性lps-induced tnfα响应.pdfVIP

Skeletal Muscle PGC-1a Is Required for Maintaining an Acute LPS-Induced TNFa Response 1 1 1 1 2 1 Jesper Olesen *, Signe Larsson , Ninna Iversen , Simi Yousafzai , Ylva Hellsten , Henriette Pilegaard 1 Centre of Inflammation and Metabolism and Copenhagen Muscle Research Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, 2 Copenhagen Muscle Research Centre, Department of Sport Sciences, University of Copenhagen, Copenhagen, Denmark Abstract Many lifestyle-related diseases are associated with low-grade inflammation and peroxisome proliferator activated receptor c coactivator (PGC)-1a has been suggested to be protective against low-grade inflammation. However, whether these anti- inflammatory properties affect acute inflammation is not known. The aim of the present study was therefore to investigate the role of muscle PGC-1a in acute inflammation. Quadriceps muscles were removed from 10-week old whole body PGC-1a knockout (KO), muscle specific PGC-1a KO (MKO) and muscle-specific PGC-1a overexpression mice (TG), 2 hours after an intraperitoneal injection of either 0.8 mg LPS/g body weight or saline. Basal TNFa mRNA content was lower in skeletal muscle of whole body PGC-1a KO mice and in accordance TG mice showed increased TNFa mRNA and protein level relative to WT, indicating a possible PGC-1a mediated regulation of TNFa. Basal p65 phosphorylation was increased in TG mice possibly explaining the elevated TNFa expression in these mice. Systemically, TG mice had reduced basal plasma TNFa levels compared with WT suggesting a protective effect against systemic low-grade inflammation in these animals. While TG mice reached similar TNFa levels as WT and