Roux-en-Y gastric bypass alters small intestine glutamine transport in the obese Zucker rat

Wolff, Brynn S.; Meirelles, Katia; Meng, Qinghe; Pan, Ming; Cooney, Robert N.

doi:10.1152/ajpgi.00104.2009

Cited by 22 publications

(28 citation statements)

References 32 publications

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“…In fact, using leptin mutein, a leptin receptor antagonist (26), we demonstrate that this modulation requires an effective interaction of leptin with its specific receptor located at the BBM of the small intestine (3,9). Interestingly, a recent report shows that, in leptin receptordeficient obese Zucker rats, Gln transport is highly increased (29). This is in line with the inhibitory action of leptin as a regulator of the Gln uptake here reported.…”

Section: Discussionsupporting

confidence: 88%

Luminal leptin inhibits l-glutamine transport in rat small intestine: involvement of ASCT2 and B⁰AT1

Ducroc

Sakar

Fanjul

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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is the primary metabolic fuel for enterocytes. Glutamine from the diet is transported into the absorptive cells by two sodium-dependent neutral amino acid transporters present at the apical membrane: ASCT2/SLC1A5 and B 0 AT1/ SLC6A19. We have demonstrated that leptin is secreted into the stomach lumen after a meal and modulates the transport of sugars after binding to its receptors located at the brush border of the enterocytes. The present study was designed to address the effect of luminal leptin on Na ϩ -dependent glutamine (Gln) transport in rat intestine and identify the transporters involved. We found that 0.2 nM leptin inhibited uptake of Gln and phenylalanine (Phe) (substrate of B 0 AT1) using everted intestinal rings. In Ussing chambers, 10 mM Gln absorption followed as Na ϩ -induced short-circuit current was inhibited by leptin in a dose-dependent manner (maximum inhibition at 10 nM; IC50 ϭ ϳ0.1 nM). Phe absorption was also decreased by leptin. Western blot analysis after 3-min incubation of the intestinal loops with 10 mM Gln, showed marked increase of ASCT2 and B 0 AT1 protein in the brush-border membrane that was reduced by rapid preincubation of the intestinal lumen with 1 nM leptin. Similarly, the increase in ASCT2 and B 0 AT1 gene expression induced by 60-min incubation of the intestine with 10 mM Gln was strongly reduced after a short preincubation period with leptin. Altogether these data demonstrate that, in rat, leptin controls the active Gln entry through reduction of both B 0 AT1 and ASCT2 proteins traffic to the apical plasma membrane and modulation of their gene expression.Ussing chamber; intestinal rings; leptin receptor; phenylalanine; qPCR GLUTAMINE (Gln) is the most abundant amino acid in the plasma. It is absorbed by the intestine, making this organ a key player in the whole body Gln homeostasis. As Gln is a precursor of the nucleosides and glucose synthesis and is involved in the acid-base balance in the kidney, it is crucial for the interorgan nitrogen flux. Gln is also the most important energy source for the enterocytes, lymphocytes, and fibroblasts and is necessary for the growth and viability of cells maintained in culture (5). Gln from the diet is transported into the enterocyte by two sodium-dependent neutral amino acid transporters present in the apical membrane: ASCT2 (System ASC) and B 0 AT1 (System B) (6). ASCT2/SLC1A5 shows high affinity for alanine (Ala), serine, cysteine, threonine, and Gln (K 0.5 ϭ ϳ20 M), whereas B 0 AT1/ SLC6A19 is a low-affinity transporter (K 0.5 ranging from 1.4 to 4 mM) with preference for large neutral amino acids, including those with bulky lateral chain as phenylalanine (Phe), a specific substrate for this transporter (6). In the cell, most of the Gln is metabolized to cover its energetic requirements, and the rest is transported to the blood by the basolateral sodium-independent exchanger LAT-2/4F2hc, SLC7A8/SLC3A2 (system L) (6).Leptin was initially described as an adipostatic signal controlling food intake and energy expenditure (32). Toda...

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Section: Discussionsupporting

confidence: 88%

Luminal leptin inhibits l-glutamine transport in rat small intestine: involvement of ASCT2 and B⁰AT1

Ducroc

Sakar

Fanjul

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…This was not further investigated because it is beyond the scope of this report. Post-RYGB alterations in intestinal glucose transport and metabolism have been recently described (28,31,36). However, because muscle represents the principal site of insulin-stimulated glucose transport in vivo, the observed increase in muscle glucose uptake presumably represents the predominant mechanism for improved glucose homeostasis after the IT procedure (14,27).…”

Section: Discussionmentioning

confidence: 98%

“…Tissues were rapidly excised and snap frozen between liquid nitrogen cooled clamps for later processing. Intestinal mucosa from the jejunum and ileum were isolated by scraping (36). Tissues were subsequently weighed and homogenized in ice-cold 0.5 N perchloric acid (0.4 ml/100 mg tissue), then centrifuged at 3,000 g for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Ileal interposition improves glucose tolerance and insulin sensitivity in the obese Zucker rat

Culnan¹,

Albaugh

Sun³

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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The hindgut hypothesis posits improvements in Type 2 diabetes after gastric bypass surgery are due to enhanced delivery of undigested nutrients to the ileum, which increase incretin production and insulin sensitivity. The present study investigates the effect of ileal interposition (IT), surgically relocating a segment of distal ileum to the proximal jejunum, on glucose tolerance, insulin sensitivity, and glucose transport in the obese Zucker rat. Two groups of obese Zucker rats were studied: IT and sham surgery ad libitum fed (controls). Changes in food intake, body weight and composition, glucose tolerance, insulin sensitivity and tissue glucose uptake, and insulin signaling as well as plasma concentrations of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide were measured. The IT procedure did not significantly alter food intake, body weight, or composition. Obese Zucker rats demonstrated improved glucose tolerance 3 wk after IT compared with the control group (P < 0.05). Euglycemic, hyperinsulinemic clamp and 1-[(14)C]-2-deoxyglucose tracer studies indicate that IT improves whole body glucose disposal, insulin-stimulated glucose uptake, and the ratio of phospho- to total Akt (P < 0.01 vs. control) in striated muscle. After oral glucose, the plasma concentration of glucagon-like peptide-1 was increased, whereas GIP was decreased following IT. Enhanced nutrient delivery to the ileum after IT improves glucose tolerance, insulin sensitivity and muscle glucose uptake without altering food intake, body weight, or composition. These findings support the concept that anatomic and endocrine alterations in gut function play a role in the improvements in glucose homeostasis after the IT procedure.

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“…In C. elegans , loss of the peptide NT PEPT-1 results in higher uptake of free fatty acids and accumulation of body fat due to an increase in [H + ] on the mucosal luminal surface [3]; conversely, loss of the sodium-proton exchanger NHX-2 leads to lower uptake of free fatty acids and reductions in body fat due to a decrease in [H + ] on the mucosal luminal surface [3]. Moreover, compared to lean littermates, obese Zucker rats demonstrate higher mRNA and protein abundance for the amino acid NT B 0 AT1 across all regions of the small intestine [4]. Obesity, as well as diabetes-related alterations in gastric emptying, may also affect nutrient absorption.…”

Section: Introductionmentioning

confidence: 99%

Nutrient Transporter Expression in the Jejunum in Relation to Body Mass Index in Patients Undergoing Bariatric Surgery

et al. 2016

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Nutrient tranters (NT) facilitate nutrient absorption and contribute to the regulation of circulating nutrients. In this cross-sectional study, we determined the associations between the level of obesity; mRNA abundance for NTs; and serum concentrations of amino acids, short-chain fatty acids, and glucose in patients with morbid obesity undergoing a Roux-en-Y gastric bypass. Proximal jejunal samples were obtained at the time of surgery from 42 patients (90% female, age = 42.6 ± 11.9 years, pre-operative body mass index (BMI) = 55.5 ± 11.3 kg/m2) undergoing a Roux-en-Y gastric bypass. RNA was extracted from the jejunal mucosa and quantitative real-time–PCR was performed for the NTs studied. BMI negatively correlated with jejunal mRNA abundance of the amino acid NTs TauT (r = −0.625, p < 0.0001), ASCT2 (r = −0.320, p = 0.039), LAT1 (r = −0.304, p = 0.05). BMI positively correlated with jejunal mRNA abundance of the lactate/short-chain fatty acid NT SMCT1 (r = 0.543, p = 0.0002). Serum concentrations of the short-chain fatty acids, butyric, valeric, and isocaproic acid correlated positively with BMI (n = 30) (r = 0.45, r = 0.44, r = 0.36, p ≤ 0.05; respectively). Lower jejunal mRNA abundance for the amino acid NTs TauT, ASCT2, and LAT1 could protect against further obesity-related elevations in circulating amino acids. The positive correlation between BMI and the jejunal mRNA abundance of the high-affinity short-chain fatty acid/monocarboxylate transporter SMCT1 is intriguing and requires further investigation.

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Roux-en-Y gastric bypass alters small intestine glutamine transport in the obese Zucker rat

Cited by 22 publications

References 32 publications

Luminal leptin inhibits l-glutamine transport in rat small intestine: involvement of ASCT2 and B⁰AT1

Luminal leptin inhibits l-glutamine transport in rat small intestine: involvement of ASCT2 and B⁰AT1

Ileal interposition improves glucose tolerance and insulin sensitivity in the obese Zucker rat

Nutrient Transporter Expression in the Jejunum in Relation to Body Mass Index in Patients Undergoing Bariatric Surgery

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Roux-en-Y gastric bypass alters small intestine glutamine transport in the obese Zucker rat

Cited by 22 publications

References 32 publications

Luminal leptin inhibits l-glutamine transport in rat small intestine: involvement of ASCT2 and B0AT1

Luminal leptin inhibits l-glutamine transport in rat small intestine: involvement of ASCT2 and B0AT1

Ileal interposition improves glucose tolerance and insulin sensitivity in the obese Zucker rat

Nutrient Transporter Expression in the Jejunum in Relation to Body Mass Index in Patients Undergoing Bariatric Surgery

Contact Info

Product

Resources

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Luminal leptin inhibits l-glutamine transport in rat small intestine: involvement of ASCT2 and B⁰AT1

Luminal leptin inhibits l-glutamine transport in rat small intestine: involvement of ASCT2 and B⁰AT1