Abstract

RYGB is still the most effective treatment of obesity and its comorbidities, but the signaling molecules and mechanisms that mediate the beneficial effects of RYGB are largely unknown. One of the classes of molecules that could be involved are gut‐derived endogenous lipids. We therefore investigated profiles of potential lipid mediators locally in the gut. We non‐occlusively cannulated the mesenteric lymph duct of diet‐induced obese (DIO), insulin‐resistant RYGB or sham‐operated rats and collected lymph samples in relation to spontaneous meals for subsequent mass spectrometry analysis of the intestinal lymphatic lipidome from all animals prior to and 5, 10 and 21 days after the surgery. A multivariate analysis revealed two separate clusters for the lipidomes of the animals of the two surgical groups. Unlike sham‐surgery, RYGB surgery changed the levels of >150 lipids compared to pre‐surgical levels. TG were mostly decreased after RYGB, presumably reflecting the reduced food intake. Some lipids, however, were increased in intestinal lymph after RYGB. Especially those reported to be decreased in obesity (e.g., lysophosphatidylcholine [LPC] 20:1 or phosphatidylcholine [PC] 32:0) were upregulated about two‐fold 21 days after the RYGB surgery. This might be related to the decreased body weight rather than being a direct surgery effect. Some lipids, however, (e.g., PC 40:7, phosphatidylethanolamines [PE] 40:6, sphingomyelins [SM] 18:0) were upregulated in the RYGB group already 5 days after surgery, long before their body weight was significantly decreased compared to sham‐operated controls. Notably, there was a strong positive correlation between RYGB surgery and longer chain length in particular for TG, diacylglycerols [DG], PE, and SM. Moreover, TG, DG and phosphatidylinositols showed a positive correlation between RYGB surgery and an increased frequency of double bonds. Whether these changes are cause or consequence of an improvement of enterocyte structure and function, and whether they contribute to the reported improvement of the various comorbidities requires further investigation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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