|
Back to 2017 Posters
GASTRIC BYPASS RESTORES INTESTINAL IL-17 AND IL-23 EXPRESSION IN DIABETIC RATS
Renuka Subramaniam*1,2, Hina Y. Bhutta1,2, Ali Tavakkoli1,2, Eric G. Sheu1,2
1Surgery, Brigham and Women's hospital, Boston, MA; 2Harvard Medical School, Boston, MA
Background: Roux-en-Y gastric bypass (RYGB) leads to remission of type 2 diabetes (T2D). Systemic inflammation associated with compromised intestinal defense against gut microbiota contributes to T2D. We hypothesize that RYGB triggers changes in intestinal mucosal immunity that are important for T2D resolution.
Methods: RYGB was performed in diabetic ZDF rats (n=6) and compared to sham-operated ZDF (n=6) and non-diabetic SD rats (n=6). RNA was isolated from mucosal scrapings of the Roux (Rx) and biliopancreatic (BP) limbs 4 weeks post-operatively. Key cytokines involved in inflammasome activation (IL-1beta, IL-18), resolution of inflammation (IL-10, IL-33), and innate lymphoid and Th17 cell responses (IL-17, IL-23) were measured by quantitative PCR. Groups were compared by ANOVA.
Results: Markedly reduced expression of IL-17 and IL-23 was seen in ZDF compared to SD rats (40 and 3 fold, respectively, p<0.001). RYGB increases expression of IL-17 and IL-23 (6.7 and 2.8 fold, p<0.05) in the BP limb of ZDF rats. In the Rx limb, RYGB mildly enhanced IL-17 but did not change IL-23. RYGB did not significantly alter IL1beta, IL-18, IL-10, or IL33 expression. Changes in intestinal cytokine expression correlated with improved glycemic control after RYGB (202±11 [RYGB] vs. 300±44 mg/dl [Sham]; p<0.001).
Conclusions: Intestinal expression of IL-17 and IL-23 is reduced in diabetic ZDF versus non-diabetic SD rats. RYGB surgery reverses this defect, primarily by augmenting IL-17 and IL-23 expression in the BP limb. Changes in intestinal mucosal immunity may play a role in the anti-diabetic effects of RYGB.
Cytokine changes after RYGB surgery in ZDF rats
| Cytokine genes | Fold change in relative mRNA expression
after RYGB in ZDF rats
| | | RX limb | BP limb | | Innate lymphoid cell / Th17 cell function | | | | IL-17 | 2.7 ±0.7 * | 6.7 ± 2.6 * | | IL-23 | ns | 2.8 ± 0.7 * | | Inflammasome activation | | | | IL-1β | ns | ns | | IL-18 | ns | ns | | Resolution of inflammation | | | | IL-10 | ns | ns | | IL-33 | ns | ns |
*p < 0.05 compared to sham control ZDF. ns: no significant change.
Back to 2017 Posters
|
