Experimental sepsis causes SERCA2 expression in white adipose tissue but not classical browning

Sepsis causes muscle wasting and cachexia but mechanisms remain unclear. Cachexia in cancer and burn injury is partly attributed to 'browning'; where white adipose tissue (WAT) develops a catabolic, thermogenic brown adipose tissue-like phenotype. We hypothesised that sepsis-induced muscle wasting is caused by browning. 58 male Wistar rats were randomised to sham (n = 17) or experimental sepsis induced by intraperitoneal zymosan (n = 41). Tibialis anterior mass was measured on Days 3 and 14. Browning was sought using whole body and WAT respirometry, RNA-sequencing, immunoblot, thermal imaging and multi-photon microscopy of WAT. Fourteen-day mortality in rats receiving zymosan was 17%. In survivors, body mass loss peaked at day 3 and persisted to day 14 with associated tibialis anterior muscle mass loss. Zymosan peritonitis caused hypermetabolism during the late recovery phase (Days 11-14), but no difference in epididymal white adipose tissue temperature nor oxygen flux. At Day 14 transcriptomics showed inflammation but no increase in uncoupling protein (UCP)-1 at transcript or protein levels. SERCA2 protein was however increased fourfold in retroperitoneal WAT at day 14 (p = 0.016). Rats recovering from zymosan peritonitis developed muscle wasting and cachexia associated with WAT inflammation and whole-body hypermetabolism. No evidence of browning was seen at functional, transcriptomic or protein levels, therefore our data do not support the hypothesis of classical browning as a driver of sepsis-induced muscle wasting and cachexia. SERCA2 protein expression was however increased in retroperitoneal WAT at day 14.