IL-22 restores glucose tolerance and alters feeding behavior in obese mice-possible effects beyond the pancreatic islet

Abstract

Introduction: IL-22 is a major regulator of glucose homeostasis. Its receptor, IL-22RA1, is most highly expressed in the beta- and alphacells of the pancreatic islets, as well as the liver and gut epithelium. 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 beta cells. In obese mice on high fat diets (HFD), IL-22 administration promoted appropriately controlled insulin secretion and improved insulin quality, suppressing fasting hyperinsulinaemia and hyperprolinsulinaemia, to first restore glucose tolerance and then improve insulin sensitivity. These metabolic improvements were accompanied by a small reduction in weight. Objectives: A preliminary study to investigate the mechanisms of IL-22-related improvements in glucose tolerance and weight loss. Methods: C57/B6 mice on a normal chow diet (NCD) or HFD were treated with i.p IgG or IL-22 every 4 days for 12 days. Nuclear magnetic resonance (NMR) was used for body composition analysis at baseline and day 12. The Phenomaster system for comprehensive serial assessment of weight gain, activity, and feeding characteristics. Beta cell function was assessed via IPGTT on day 12. Results: In this preliminary study, IL-22 administration did not significantly alter weight gain, cumulative activity, or oxygen consumption between groups. IL-22 improved glucose tolerance [AUC (glucose), mean ± SEM] in both NCD (1,263 ± 56 vs 1,168 ± 73, p < 0.05) and HFD (1,540 ± 65 vs 1,155 ± 92, p < 0.01) mice. Cumulative food intake (grams, mean ± SEM) was reduced in IL-22-treated HFD mice (45.2 ± 2.2 vs 37.6 ± 0.9, p < 0.05). Conclusions: These results suggest a possible beneficial effect of IL- 22 on the regulation of satiety, either secondary to, or in addition to, effects in the pancreatic islet. Further studies are planned to further delineate the relationship between IL-22, the beta cell, and gut / hypothalamic satiety signaling.L720733322015-11-20 <br />