5‐Aminosalicylic Acid Treatment Affects the Rate of Caloric Intake in Fattening Ground Squirrels

Abstract

Obesity is the second leading cause of preventable death in the United States. Though prevalent, very little is known about the biological mechanisms that lead to obesity. A connection between increased gut permeability and the consequent immune response in systemic tissues exists in obese humans and mice. Systemic inflammation brought on by this immune response has been shown to decrease tissue efficacy and lead to adverse effects, such as insulin resistance. Recently, it was shown in mice on a high‐fat diet that 5‐aminosalicylic acid (5‐ASA, mesalazine), a gut‐specific anti‐inflammatory drug, attenuated insulin resistance and metabolic inflammation. We used a natural model of rapid adiposity, fattening 13‐lined ground squirrels (Ictidomys tridecemlineatus) during their active season, to examine the effects of 5‐ASA on caloric intake, body mass, glucose tolerance and inflammation. These squirrels normally double their adipose mass during their active season in preparation for hibernation. We found that the rate of caloric intake was significantly affected by 5‐ASA treatment and that these squirrels tended to eat more while gaining equal or less mass during the same period. Adipose depot mass was not different between groups but did differ between males and females. Despite a trend in the early weeks of 5‐ASA treatment, glucose tolerance did not differ between treated and control squirrels. Examination of pro‐ and anti‐inflammatory cytokines in white adipose depots and gut tissues revealed trends toward increased IL‐4 and TNF in visceral adipose of treated squirrels. Our results suggest that 5‐ASA treatment has different effects on development of metabolic inflammation in ground squirrels versus mice. Further studies are needed to determine if a higher dose would prove more effective in these seasonal hibernators.Support or Funding InformationSupported by NIH award 1R15GM124586‐01A1