Hyperglycemia remission after Roux-en-Y gastric bypass: Implicated to altered monocyte inflammatory response in type 2 diabetes rats

Hyperglycemia remission by metabolic surgery is implicated in the resolution of low-grade inflammation in type 2 diabetes mellitus (T2DM). However, whether this beneficial effect of metabolic surgery is related to improving monocyte inflammatory response remains undefined. This investigation is addressed to evaluate this relation-ship. For this purpose, T2DM rats were subjected to Roux-en-Y gastric bypass (RYGB) and/or monocyte depletion or splenic sympathetic denervation. Fasting blood glucose (FBG), plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) were measured, and monocyte inflammatory response was assessed in vitro. The data showed that RYGB significantly reduced lipopolysaccharide (LPS)-induced release of TNF-alpha and IL-1 beta from peripheral monocytes while alleviating hyperglycemia and reducing plasma TNF-alpha and IL-1 beta levels. Hypergly-cemia resulting from monocyte depletion by injection of clodronate liposomes resolved one week earlier than vehicle control after RYGB. Splenic denervation abrogated the glucose-lowering effect and decreased LPS-stimulated TNF-alpha and IL-1 beta release from monocytes following RYGB. Overall, our results reveal that a marked reduction of monocyte inflammatory response after RYGB contributes to hyperglycemia remission in T2DM rats. The beneficial effect of RYGB is mediated through vagal-spleen axis anti-inflammatory activity.