Treatment with Gut-Specific Nonsteroidal Anti-Inflammatory Drug Attenuates Metabolic Inflammation but not Body Mass in Fattening Ground Squirrels

The active season of hibernators corresponds to rapid adiposity in preparation for the next hibernation season. We have previously shown that this dramatic increase in adipose mass is associated with metabolic inflammation similar to what is seen in obesity and metabolic disease. We next sought to determine whether curbing this inflammation at its source (i.e., the gut) would attenuate weight gain in fattening 13-lined ground squirrels ( Ictidomys tridecemlineatus). We fed active yearling ground squirrels a diet containing the gut-specific non-steroidal anti-inflammatory drug mesalazine (5-aminosalicylic acid) for 10 weeks. Mesalazine treatment had slight effects on microbial community diversity in cecum and colon. Not surprisingly, mesalazine treatment decreased inflammatory cytokine levels in the ileum and colon. Mesalazine also decreased pro-inflammatory and increased anti-inflammatory cytokines in omental white adipose tissue (oWAT). Despite this, body mass was unaffected and caloric intake increased in mesalazine-treated squirrels, mainly in males. Mass of the primary WAT depot, intra-abdominal WAT (iaWAT), or the highly metabolic oWAT were unaltered by treatment, as was adiposity index. Together, these results suggest that mesalazine treatment has some effects on adiposity in fattening ground squirrels, but this treatment needs to be modified to overcome the strong drive to fatten in this species.