RESUMEN
Roux-en-Y gastric bypass (RYGB) is one of the most performed bariatric surgical techniques. However, RYGB commonly results, as side effects, in nutritional deficiencies. This study aimed to examine changes in the expression of vitamin A pathway encoding genes in the gastrointestinal tract (GI) and to evaluate the potential mechanisms associated with hypovitaminosis A after RYGB. Intestinal biopsies were obtained through double-balloon endoscopy in 20 women with obesity (age 46.9±6.2 years; body mass index [BMI] 46.5±5.3 kg/m2 [mean±SD]) before and three months after RYGB (BMI, 38.2±4.2 kg/m2). Intestinal mucosal gene microarray analyses were performed in samples using a Human GeneChip 1.0 ST array (Affymetrix). Vitamin A intake was assessed from 7-day food records and serum retinol levels were evaluated by electrochemiluminescence immunoassay. Our results showed the following genes with significant downregulation (p≤0.05): LIPF (-0.60), NPC1L1 (-0.71), BCO1 (-0.45), and RBP4 (-0.13) in duodenum; CD36 (-0.33), and ISX (-0.43) in jejunum and BCO1 (-0.29) in ileum. No significant changes in vitamin A intake were found (784±694 retinol equivalents [RE] pre-operative vs. 809±753 RE post-operative [mean±SD]). Although patients were routinely supplemented with 3500 international units IU/day (equivalent to 1050 µg RE/day) of oral retinol palmitate, serum concentrations were lower in the post-operative when compared to pre-operative period (0.35±0.14 µg/L vs. 0.52±0.33 µg/L, respectively - P=0.07), both within the normal range. After RYGB, the simultaneous change in expression of GI genes, may impair carotenoid metabolism in the enterocytes, formation of nascent chylomicrons and transport of retinol, resulting in lower availability of vitamin A.
RESUMEN
OBJECTIVES: Vitamin B12 (B12) deficiency after Roux-en-Y gastric bypass (RYGB) is highly prevalent and may contribute to postoperative complications. Decreased production of intrinsic factor owing to gastric fundus removal is thought to have a major role, but other components of B12 metabolism may also be affected. We evaluated changes in the expression levels of multiple B12 pathway-encoding genes in gastrointestinal (GI) tissues to evaluate the potential roles in contributing to post-RYGB B12 deficiency. METHODS: During double-balloon enteroscopy, serial GI biopsies were collected from 20 obese women (age, 46.9±6.2 years; body mass index, 46.5±5.3 kg/m2) with adult-onset type 2 diabetes (fasting plasma glucose ≥126 mg/dl; hemoglobin A1c≥6.5%) before and, at the same site, 3 months after RYGB. Gene expression levels were assessed by the Affymetrix Human GeneChip 1.0 ST microarray. Findings were validated by real-time quantitative PCR (RT-qPCR). RESULTS: Gene expression levels with significant changes (P≤0.05) included: transcobalamin I (TCN1) in remnant (-1.914-fold) and excluded (-1.985-fold) gastric regions; gastric intrinsic factor (GIF) in duodenum (-0.725-fold); and cubilin (CUBN) in duodenum (+0.982-fold), jejunum (+1.311-fold), and ileum (+0.685-fold). Validation by RT-qPCR confirmed (P≤0.05) observed changes for TCN1 in the remnant gastric region (-0.132-fold) and CUBN in jejunum (+2.833-fold). CONCLUSIONS: RYGB affects multiple pathway-encoding genes that may be associated with postoperative B12 deficiency. Decreased TCN1 levels seem to be the main contributing factor. Increased CUBN levels suggest an adaptive genetic reprogramming of intestinal tissue aiming to compensate for impaired intestinal B12 delivery.