Background: IL-22 is a major regulator of mucosal integrity and tissue repair. In the pancreas, the IL-22 receptor- IL-22RA1, is most highly expressed in the β- and α-cells of the pancreatic islets. We have previously shown that islet-endogenous and exogenous IL-22 suppresses oxidative and ER stress caused by cytokines and glucolipotoxicity in murine and human islets. IL-22 administration in obese mice on high fat diets (HFD), improved insulin quality, suppressing fasting hyperinsulinaemia and hyperprolinsulinaemia, which primarily restored glucose tolerance, and then later improved insulin sensitivity. These metabolic improvements were accompanied by a small reduction in weight. We aimed to investigate the mechanisms of IL-22-related weight loss.
Methods: C57/BL6 mice (n=8/group) on a normal chow diet (NCD) or HFD were treated with i.p PBS or IL-22 (100 ng/g) every 4 days for a total of 12 days. Nuclear magnetic resonance (NMR) was used for body composition analysis at baseline and day 12. The Phenomaster system was used for a comprehensive assessment of weight gain, activity, and feeding characteristics. Gene expression analysis using RT-PCR was performed on a subset of mice (n=4/group).
Results: Short-term IL-22 administration did not significantly alter weight gain, oxygen consumption, or cumulative activity between groups. However, cumulative food intake (grams, mean ± SD) was reduced in IL-22-treated HFD mice (52.1 + 5.3 vs 44.4 + 6.7, p<0.05). Ex-vivo mRNA analysis of hypothalamus suggested that IL-22 may effect satiety by increasing the expression of the anorexigenic gene pro-opiomelanocortin.
Conclusions: These results suggest a possible beneficial effect of IL-22 on the regulation of satiety. Further studies are planned to delineate the relationship between IL-22, the beta cell, and gut/hypothalamic satiety signaling and whether these effects are directly or indirectly regulated by the potential effect of IL-22 on the hypothalamus.