RYGB Mediated Lipid Metabolism Changes Contribute to T2D Resolution
*Tammy Lo, *Renuka Subramaniam, Eric G Sheu, Ali Tavakkoli
Brigham and Women's Hospital, Boston, MA
Objective: Roux-en-Y gastric bypass (RYGB) induces weight loss and type-2 diabetes remission. We hypothesized that RYGB benefits metabolically via benefits driven by changes in gut nutrient metabolism, which in turns alter portal vein milieu.
Design: Sprague-Dawley rats were randomized to sham or RYGB. Systemic and portal blood samplings were performed by jugular and portal vein catheterization 5 weeks after surgery. Roux (Rx), biliopancreatic (BP) and common (CL) limbs in RYGB rats along with their respective sham counterparts were harvested. Lipid metabolites characterization was performed by a lipidomics strategy using liquid chromatography coupled to mass spectrometry. RNA expressions of fatty acid (FA) uptake transporters and FA β-oxidation proteins were measured.
Setting: Academic research laboratories.
Patients: N/A.
Interventions: RYGB comprised of a stapled, divided gastric pouch with a 16cm BP limb and a 10cm Rx limb. Sham rats received a jejunal transection and re-anastomosis.
Main Outcome Measures: N/A.
Results: RYGB led to a -21.6% weight change vs. 11.4% in Sham rats (p<0.001). RYGB rats showed an improvement in glucose tolerance at 4 weeks. Diglycerides and triglycerides levels were downregulated in portal serum reflective of the decrease in intestinal absorption. Upregulation of longer chain phospholipids (phosphatidylcholine) was seen after RYGB. RNA expressions of FA uptake transporters (fatp1, cd36) and intracellular FA binding protein 2 (fabp2) were reduced after RYGB. Gene expression for FA β-oxidation (slc27a2, slc22a5, cpt1b, cpt2) has also significantly downregulated.
Conclusions: Changes in intestinal FA uptake and enterocyte FA β-oxidation after RYGB leads to changes in intestinal energy utilization and subsequent changes in portal vein milieu, which in turn may lead to improving hepatic glucose utilization.
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