Inability to replete white adipose tissue during recovery phase of sepsis is associated with increased autophagy, apoptosis, and proteasome activity

Adipose tissue is an important energy depot and endocrine organ, and the degree of adiposity impacts the host response to infection. However, little is known regarding the mechanisms by which white adipose tissue (WAT) is lost acutely and then restored after the resolution of sepsis. Therefore, the signaling pathways governing protein synthesis, autophagy, apoptosis, and the ubiquitin-proteasome were investigated to identify potential mechanisms mediating the acute (24 h) loss of WAT after cecal ligation and puncture as well as the failure to replenish WAT during recovery (day 10). While whole body fat mass was decreased equally in pair-fed control and septic mice at 5 days after cecal ligation and puncture, fat mass remained 35% lower in septic mice at day 10. During sepsis-recovery, protein synthesis in epididymal WAT was increased compared with control values, and this increase was associated with an elevation in eukaryotic translation initiation factor (eIF)2B but no change in mammalian target of rapamycin complex 1 activity (eIF4E-binding protein-1 or S6 kinase 1 phosphorylation). Protein breakdown was increased during sepsis-recovery, as evidenced by the elevation in ubiquitin-proteasome activity. Moreover, indexes of autophagy (light chain 3B-II, autophagy-related protein 5/12, and beclin) were increased during sepsis-recovery and associated with increased AMP-activated kinase-dependent Ser555-phosphorylated Unc-51-like autophagy activating kinase-1. Apoptosis was incr...

Source: AJP: Regulatory, Integrative and Comparative Physiology - March 9, 2017 Category: Physiology Authors: Crowell, K. T., Soybel, D. I., Lang, C. H. Tags: Research Article Source Type: research