Intestinal Glucose and Lipid Metabolism are Altered in Gastric Bypass Mediated Type 2 Diabetes Resolution
Renuka Subramaniam DVM, PhD, Hina Y Bhutta MD, Stanley Ashley MD, Eric G Sheu MD, PhD, Ali Tavakkoli MD
Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Background: Background: Roux-en -Y gastric bypass surgery (RYGB) is the gold-standard treatment for obesity and type 2 diabetes (T2D). Changes in intestinal physiology drive these metabolic benefits, although detailed mechanistic data is lacking. We hypothesized that direct changes in intestinal nutrient utilization contribute to the anti-T2D effect of surgery.
Methods: RYGB or sham surgery was performed in diabetic (ZDF; n=6/group) and non-diabetic (SD; n=5/group) rats. At 4 weeks, intestinal tissues were collected and detailed microarray analysis performed to identify metabolic pathways altered by surgery. Candidate genes were validated by qPCR. Genes of interest were further studied in matched patient jejunal tissue (obese diabetic vs. obese non-diabetic; n=6/group).
Results: RYGB significantly decreased weight and lowered systemic glucose levels (p<0.05). In the proximal bowel, ZDF rats had increased fatty acid transport and oxidation gene expression compared to SD rats (>5 fold; p<0.08). Similarly, diabetic patients had increased expression of fatty acid metabolic genes. RYGB significantly reduced the expression level of genes involved in fatty acid uptake, transport and oxidation (SLC and CPT) in both the Roux (Rx) and biliopancreatic (BP) limbs (p<0.001-0.07) of ZDF rats (Table1). Together, intestinal metabolic profiling confirms a switch from fatty acid to glucose utilization induced by RYGB.
Conclusion: In diabetic rodents and patients, the proximal bowel demonstrates a preference to utilize fatty acids. RYGB restores intestinal fatty acid oxidation to non-diabetic levels and enhance glucose utilization.
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