Roux-en-Y gastric bypass affects the expression of genes related to the intestinal folate metabolism pathway in obese women.

OBJECTIVES: Roux-en-Y gastric bypass (RYGB) promotes sustained weight loss, and the resulting new gastrointestinal anatomy can contribute to nutritional depletions. Folate deficiency is one of the most frequently observed nutritional deficiencies after RYGB. The aim of this study was to assess whether RYGB affects the expression of genes related to the intestinal folate metabolism pathway as an additional molecular mechanism contributing to its postoperative deficiency. METHODS: Biopsies from the duodenum, jejunum, and ileum of 20 obese women were collected before and 3 mo after RYGB. The expression of genes involved in intestinal folate metabolism was assessed by microarray and reverse transcriptase polymerase chain reaction (RT-qPCR). Folate intake (7-d food record) and plasma levels (electrochemiluminescence) also were measured. RESULTS: Compared with the preoperative phase, transcriptomic alterations were observed in all intestinal segments studied after RYBG, mainly marked by decreased expression of genes encoding folate transporters/receptors and increased expression of genes involved in folate biosynthesis (P < 0.05). Reduced folate intake and plasma folate levels were also observed simultaneously (P < 0.05). Plasma folate concentrations correlated inversely with intestinal FOLR2 and SHMT2 genes (P < 0.001). CONCLUSION: The present findings suggested that impaired expression of genes related to intestinal folate metabolism may contribute to the early systemic deficiency after RYGB and highlight a potential transcriptomic reprogramming of the intestine in response to RYGB to compensate for folate depletion induced by this surgical technique.

Gastrointestinal genetic reprogramming of vitamin A metabolic pathways in response of Roux-en-Y gastric bypass.

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.

Tissue-specific methylation profile in obese patients with type 2 diabetes before and after Roux-en-Y gastric bypass.

Eating habits, lifestyles, and exposure to specific environmental factors can greatly impact the risk of developing type 2 diabetes (T2D), influence the genome epigenetically, and affect the expression of genes, including genes related to glycemic control, at any stage of life. The epigenetic mechanism underlying obesity and T2D pathogenesis remains poorly understood. Conventional strategies for the treatment of obesity and its comorbidities often have poor long-term adherence, and pharmacological interventions are limited. Bariatric surgery is the most effective current option to treat severe obesity, and Roux-en-Y gastric bypass (RYGB) is the most applied technique worldwide. Epigenetic changes differ depending on the approach used to treat obesity and its associated comorbidities (clinical or surgical). Compared to primary clinical care, bariatric surgery leads to much greater loss of body weight and higher remission rates of T2D and metabolic syndrome, with methylation profiles in promoter regions of genes in obese individuals becoming similar to those of normal-weight individuals. Bariatric surgery can influence DNA methylation in parallel with changes in gene expression pattern. Changes in clinical biomarkers that reflect improvements in glucose and lipid metabolism after RYGB often occur before major weight loss and are coordinated by surgery-induced changes in intestinal hormones. Therefore, the intestine methylation profile would assist in understanding the mechanisms involved in improved glycemic control after bariatric surgery. The main objectives in this area for the future are to identify epigenetic marks that could be used as early indicators of metabolic risk, and to develop treatments able to delay or even reverse these epigenetic changes. Studies that provide the "human epigenetic profile" will be of considerable value to identify tissue-specific epigenetic signatures and their role in the development of chronic diseases. Further studies should apply methods based on global analysis of the genome to identify methylated sites associated with disease and epigenetic marks associated with the remodeling response to bariatric surgery. This review describes the main epigenetic alterations associated with obesity and T2D and the potential role of RYGB in remodeling these changes.

Design of quality indicators for oral nutritional therapy.

OBJECTIVE: Quality indicators in nutritional therapy (NT) have been proposed as useful tools to improve clinical NT. This study was conducted to develop feasible quality indicators in oral nutritional therapy (QIONTs) to aid quality control. METHODS: A Clinical Nutrition Task Force composed of Brazilian NT experts from the International Life Science Institute (ILSI) developed QIONTs. In an internet-based psychometric survey, 40 independent Brazilian NT practitioners assessed four attributes (simplicity, utility, objectivity, and low cost) of each QIONT using a five-point Likert scale. RESULTS: Independent NT experts consistently classified all 12 QIONTs developed by the ILSI team as good (mean Cronbach's alpha = 0.84). In ranked order, the QIONTs enable assessment of the frequency of nutritional screening, oral nutritional supplementation (ONS) prescription to malnourished patients receiving an oral diet, ONS prescription to patients receiving an oral diet but at risk of malnutrition, nutritional assessment, adhesion to ONS regime, hospitalized patients with insufficient oral dietary intake and ONS prescription, ICU patients with insufficient oral dietary intake and ONS prescription, oral intake assessment in ICU patients, oral intake assessment in ward patients, oral supplement volume intolerance due to inappropriate offering time, ONS flavor intolerance, and ONS volume intolerance. CONCLUSION: Twelve potentially feasible new QIONTs were developed and approved for clinical practice by experts.

Objetivo: los indicadores de calidad en la terapia nutricional han sido propuestos como herramientas útiles para mejorar la terapia nutricional (TN). Este estudio pretende diseñar indicadores de calidad de terapia nutricional oral (ICTNO) factibles en el control de calidad de TN oral. Métodos: el diseño de ICTNO fue realizado por una comisión de nutrición clínica compuesta por brasileños expertos en TN del International Life Science Institute (ILSI). Más tarde, la aprobación de estos ICTNO fue valorada con análisis psicométricos recogiendo las opiniones de otros brasileños dedicados independientemente a la TN (n = 40) vía SurveyMonkey (encuesta por internet). Esta consistió en cuatro atributos valorando cada ICTNO (simplicidad, utilidad, objetividad y bajo precio) seguida de una escala Likert con cinco puntos. Resultados: los expertos en TN de ILSI proporcionaron el diseño de 12 QIONT, que fueron todos consistentemente (Alfa de Cronbach = 0,84) clasificados como válidos por expertos independientes en NT. Por orden de relevancia, los nuevos ICTNO valoraron: la frecuencia de screening nutricional, la prescripción de suplementos de nutrición oral para pacientes desnutridos que ya reciben dieta oral, la prescripción de suplementos de nutrición oral para pacientes con bajo riesgo nutricional que ya reciben dieta oral, el consejo nutricional, la adhesión al suplemento nutricional oral, los pacientes hospitalizados con dieta oral insuficiente y prescripción de suplementos nutricionales orales, los pacientes de UCI con dieta oral insuficiente y prescripción de suplementos nutricionales orales, el consejo de nutrición oral en pacientes de UCI, el consejo de nutrición oral en pacientes en planta, la intolerancia al volumen de suplemento oral debido a dosificación inadecuada, la intolerancia al sabor del suplemento oral y la intolerancia al volumen de suplemento oral. Conclusión: según la opinión experta, 12 potenciales y factibles nuevos ICTNO fueron diseñados y aprobados para la práctica clínica.

Parenteral fish oil as a pharmacological agent to modulate post-operative immune response: a randomized, double-blind, and controlled clinical trial in patients with gastrointestinal cancer.

BACKGROUND: Fish oil-based lipid emulsions (FOLEs) have shown post-operative immunological and clinical benefits in parenteral nutrition. AIM: To assess post-operative immune response after short-term pre-operative parenteral infusion of isolated FOLE in gastrointestinal cancer patients. METHODS: The patients (n = 63) received pre-operative peripheral infusion (0.2 g fat/kg body weight/d) of FOLE (Omegaven(®)) or control lipid emulsion (MCT/LCT; Lipovenos MCT(®)) for 3 days. Post-operative concentrations of inflammatory mediators, leukocyte functions, surface molecules, infections, and length of intensive care unit (ICU) and hospital stay were measured. RESULTS: FOLE patients had a significant increase of IL-10 levels on day 3, decrease of IL-6 and IL-10 levels on day 6, lower decrease in leukocyte oxidative burst, maintenance of monocyte percentage expressing HLA-DR and CD32, and increase of CD32 neutrophil expression compared to MCT/LCT patients. No changes were observed in the frequency of post-operative infections or length of ICU and hospital stay. CONCLUSIONS: Short-term pre-operative infusion of FO alone improves the post-operative immune response of gastrointestinal cancer patients without significantly changing post-operative infections or length of ICU and hospital stay. ID:NCT01218841.