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Roux-en-Y gastric bypass surgery reprograms enterocyte triglyceride metabolism and postprandial secretion in rats.

ABSTRACT: OBJECTIVE:Roux-en-Y gastric bypass (RYGB) surgery produces rapid and persistent reductions in plasma triglyceride (TG) levels associated with fewer cardiovascular events. The mechanisms of the reduction in systemic TG levels remain unclear. We hypothesized that RYGB reduces intestinal TG secretion via altered enterocyte lipid handling. METHODS:RYGB or Sham surgery was performed in diet-induced obese, insulin-resistant male Sprague-Dawley rats. First, we tested whether RYGB reduced test meal-induced TG levels in the intestinal lymph, a direct readout of enterocyte lipid secretion. Second, we examined whether RYGB modified TG enterocyte secretion at the single lipid level and in comparison to other lipid subclasses, applying mass spectrometry lipidomics to the intestinal lymph of RYGB and Sham rats (0-21 days after surgery). Third, we explored whether RYGB modulated the metabolic characteristics of primary enterocytes using transcriptional and functional assays relevant to TG absorption, reesterification, storage in lipid droplets, and oxidation. RESULTS:RYGB reduced overall postprandial TG concentrations compared to Sham surgery in plasma and intestinal lymph similarly. RYGB reduced lymphatic TG concentrations more than other lipid subclasses, and shifted the remaining TG pool towards long-chain, unsaturated species. In enterocytes of fasted RYGB rats, lipid uptake was transcriptionally (Fatp4, Fabp2, Cd36) and functionally reduced compared to Sham, whereas TG reesterification genes were upregulated. CONCLUSION:Our results show that RYGB substantially reduces intestinal TG secretion and modifies enterocyte lipid absorption and handling in rats. These changes likely contribute to the improvements in the plasma TG profile observed after RYGB in humans.

SUBMITTER: Kaufman S

PROVIDER: S-EPMC6480308 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Roux-en-Y gastric bypass surgery reprograms enterocyte triglyceride metabolism and postprandial secretion in rats.

Kaufman Sharon S Arnold Myrtha M Diaz Abdiel Alvarado AA Neubauer Heike H Wolfrum Susanne S Köfeler Harald H Langhans Wolfgang W Krieger Jean-Philippe JP

Molecular metabolism 20190313

<h4>Objective</h4>Roux-en-Y gastric bypass (RYGB) surgery produces rapid and persistent reductions in plasma triglyceride (TG) levels associated with fewer cardiovascular events. The mechanisms of the reduction in systemic TG levels remain unclear. We hypothesized that RYGB reduces intestinal TG secretion via altered enterocyte lipid handling.<h4>Methods</h4>RYGB or Sham surgery was performed in diet-induced obese, insulin-resistant male Sprague-Dawley rats. First, we tested whether RYGB reduced ...[more]

PMID: 30905616

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Project description:BackgroundExcess visceral adipose tissue predicts for incipient diabetes mellitus and cardiovascular disease. Human data are mixed regarding the benefits of selective visceral adipose tissue reduction. We investigated the effects of omentectomy added to laparoscopic Roux-en-Y gastric bypass on glucose homeostasis and lipids, inflammatory markers, and adipokines 90 days postoperatively in nondiabetic patients at the Legacy Good Samaritan Hospital and Oregon Health and Science University (Portland, OR).MethodsA single-blind, randomized study of laparoscopic Roux-en-Y gastric bypass plus omentectomy versus laparoscopic Roux-en-Y gastric bypass alone in 28 subjects (7 men and 21 women). The groups were matched at baseline for gender, age, and body mass index (BMI). The eligibility criteria included age ?18 years, BMI ?40 and <50 kg/m(2) without co-morbid conditions or BMI ?35 and <50 kg/m(2) with co-morbid conditions. The primary outcome measures were changes in the fasting plasma glucose, insulin, and homostatic model assessment of insulin resistance. The secondary measures were BMI and the high-sensitivity C-reactive protein, tumor necrosis factor-?, interleukin, total and high-molecular-weight adiponectin, fibrinogen, and plasminogen activator inhibitor-1 levels.ResultsAfter surgery, the BMI decreased significantly in both groups and was not different at the follow-up point. Although many outcome parameters improved with weight loss in both groups postoperatively, only the omentectomy group experienced statistically significant decreases in fasting glucose (P < .05), total (P = .004) and very-low-density lipoprotein (P = .001) cholesterol, and an increase in the high-molecular-weight/total adiponectin ratio (P = .013).ConclusionsOmentectomy added to laparoscopic Roux-en-Y gastric bypass results in favorable changes in glucose homeostasis, lipid levels, and adipokine profile at 90 days postoperatively. These data support the hypothesis that selective ablation of visceral adipose tissue conveys metabolic benefits in nondiabetic humans.

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Roux-en-Y gastric bypass surgery reprograms enterocyte triglyceride metabolism and postprandial secretion in rats.

Publications

Roux-en-Y gastric bypass surgery reprograms enterocyte triglyceride metabolism and postprandial secretion in rats.

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