Intestinal Glucose Transport Research Articles

Fructose co-ingestion to increase carbohydrate availability in athletes.

Carbohydrate availability is important to maximize endurance performance during prolonged bouts of moderate‐ to high‐intensity exercise as well as for acute post‐exercise recovery. The primary form of carbohydrates that are typically ingested during and after exercise are glucose (polymers). However, intestinal glucose absorption can be limited by the capacity of the intestinal glucose transport system (SGLT1). Intestinal fructose uptake is not regulated by the same transport system, as it largely depends on GLUT5 as opposed to SGLT1 transporters. Combining the intake of glucose plus fructose can further increase total exogenous carbohydrate availability and, as such, allow higher exogenous carbohydrate oxidation rates. Ingesting a mixture of both glucose and fructose can improve endurance exercise performance compared to equivalent amounts of glucose (polymers) only. Fructose co‐ingestion can also accelerate post‐exercise (liver) glycogen repletion rates, which may be relevant when rapid (<24 h) recovery is required. Furthermore, fructose co‐ingestion can lower gastrointestinal distress when relatively large amounts of carbohydrate (>1.2 g/kg/h) are ingested during post‐exercise recovery. In conclusion, combined ingestion of fructose with glucose may be preferred over the ingestion of glucose (polymers) only to help trained athletes maximize endurance performance during prolonged moderate‐ to high‐intensity exercise sessions and accelerate post‐exercise (liver) glycogen repletion.

Impairments in Protein Digestion and Absorption Attenuate the Anabolic Response to Feeding in Patients with Congestive Heart Failure (FS09-03-19)

ObjectivesGastrointestinal symptoms are prevalent extracardiac systemic manifestations of Congestive Heart Failure (CHF). We developed a comprehensive panel of methods to unravel gut dysfunction in CHF and its impact on the anabolic response to feeding. MethodsWe recruited 14 clinically stable CHF patients (ejection fraction: 33.9 ± 2.1, NYHA class: 2.3 ± 0.2) and 17 healthy controls matched for age and gender. Stable tracers of L-phenylalanine (PHE)-[ring-2H5] and L-tyrosine (TYR)-[13C9,15 N] were administered intravenously for 5 hours via primed constant and continuous infusion. After 2 hours, participants ingested a complete high protein meal containing L-PHE-[1–13C] and spirulina-[U-15 N]. We sampled blood throughout the study to analyze enrichments by LC-MS/MS. We calculated the anabolic response to feeding before and after correction for changes in protein digestion and absorption, assessed by spirulina degradation ratio (L-PHE-[15 N]/[1–13C]). Moreover, we measured small intestinal membrane integrity and active carrier-mediated glucose transport by urinary recovery of the orally ingested inert sugars lactulose, rhamnose, and 3-O-methyl-glucose. Disease severity was assessed by medical chart and history. Statistical analysis was performed by unpaired t-tests. Data are expressed as mean ± SEM. ResultsIn CHF patients, protein digestion and absorption were reduced (0.66 ± 0.04 vs. 0.82 ± 0.04, P < 0.01), which further attenuated the anabolic response to feeding (28.3 ± 3.8 vs. 54.0 ±5.5 μmol/kg FFM/meal, P < 0.001). Disturbances in protein digestion and absorption as well as anabolic response in CHF were independent of disease severity. Small intestinal permeability and active carrier-mediated glucose transport did not differ between the groups indicating a preserved enterocyte function in CHF patients. ConclusionsWe hypothesize that enhancing protein digestion and absorption in patients with CHF can improve the availability of nutrients and protein anabolism. Funding SourcesNational Institutes of Health

Effects of Acute Swimming Exercise on Pancreatic Enzyme Activity and Intestinal Glucose Transporters in Rats

PURPOSE: It has been reported that long-term endurance exercise training increases pancreatic amylase activity in rats, suggesting that chronic exercise training enhances the carbohydrate digestive capacity. To clarify whether an acute bout of endurance exercise can also induce the pancreatic adaptation and affect glucose transport capacity in small intestine as well, we evaluate the effects of acute swimming exercise with different duration on pancreatic amylase activity and intestinal glucose transporter contents in rats. METHODS: Male Sprague-Dawley rats performed acute bout of swimming exercise for 1 h (Ex-1h group) or 6 h (Ex-6h group, two 3-h bouts separated by 1h of rest). Sedentary rats were used as a control (Con group). Immediately and 24 h after the exercise, pancreas and small intestine (jejunum) were dissected out and amylase activity and glucose transporters (GLUT2 and SGLT1) content were measured, respectively. RESULTS: While no significant difference in total pancreatic amylase activity was observed between the Con and Ex-1h groups, the Ex-6h group had significantly lower total amylase activity compared with the Con group in both immediately (1233 ± 229 vs. 2088 ± 205 U, p < 0.05) and 24 h after the exercise (1295 ± 112 vs. 1954 ± 227 U, p < 0.05). There were no significant differences in GLUT2 and SGLT1 protein contents among the three groups. CONCLUSIONS: These results suggest that acute bout of prolonged exercise for longer time (~6 h) may decrease the carbohydrate digestive capacity in the rat pancreas through the diminished amylase activity, although it has little effect on intestinal glucose transporters content.

In Vitro Effects of Zinc Oxide Nanoparticles on Electrophysiological Indices and Sodium-Dependent Glucose Transport Across Jejunal Mucosa in Laying Hens

SUMMARY As nanoparticles (NPs) are readily absorbed across gastrointestinal tract, it is hypothesized that Zinc oxide nanoparticles (ZnO-NPs) will not interfere with intestinal glucose transport. The current study aims to investigate the in vitro effects of ZnO-NPs on Na linked glucose transport across jejunal mucosa in laying hens. A total of 12 White Leghorn laying hens (1.73 ± 0.176 kg), 40 wk of age, housed in individual cages were killed and mid-jejunum was divided into 4 segments to be mounted on the Ussing chambers. The mucosal side of jejunum was bathed with either no ZnO, ZnO (70 μM), ZnO-NPs (70 μM), or ZnO-NPs (35 μM) followed by addition of D-glucose (10 mM) mucosally in all the 4 experimental groups. Peak electrical response was measured 2 min after the addition of D-glucose. Results demonstrate that there was a decrease (P

Enterococcus faecalis YM0831 suppresses sucrose-induced hyperglycemia in a silkworm model and in humans

Hyperglycemia caused by excessive intake of sucrose leads to lifestyle-related diseases such as diabetes. Administration of a lactic acid bacterial strain to mice suppresses sucrose-induced hyperglycemia, but evidence for a similar effect in humans is lacking. Here we show that Enterococcus faecalis YM0831, identified using an in vivo screening system with silkworms, suppressed sucrose-induced hyperglycemia in humans. E. faecalis YM0831 also suppressed glucose-induced hyperglycemia in silkworms. E. faecalis YM0831 inhibited glucose uptake by the human intestinal epithelial cell line Caco-2. A transposon insertion mutant of E. faecalis YM0831, which showed decreased inhibitory activity against glucose uptake by Caco-2 cells, also exhibited decreased inhibitory activity against both sucrose-induced and glucose-induced hyperglycemia in silkworms. In human clinical trials, oral ingestion of E. faecalis YM0831 suppressed the increase in blood glucose in a sucrose tolerance test. These findings suggest that E. faecalis YM0831 inhibits intestinal glucose transport and suppresses sucrose-induced hyperglycemia in humans.

A Case Report of Glucose-Galactose Malabsorption in Iranian Child

Introduction Glucose-Galactose Malabsorption (GGM) is an autosomal recessive and rare disorder of intestinal transport of glucose and sodium-glucose cotransporter type (SGLT1). Case Report Our patient is a 32-day-old boy who was examined for severe diarrhea and acidosis and was treated with GGMdiagnosis. A number of laboratory tests were performed on this patient as well as positive test for reduced substance of stool and positive hydrogen breath test. On the other hand, the improvement of diarrhea with fasting and the initiation of a glucose and galactose free formula (fructose-basedformula [galactomin B-19]) was instructed. He was treated and followed with diagnosis of GGM. Conclusion In summary, careful clinical observation, laboratory tests, and the character of the external cues may provide indications of GGM.

Metformin acutely lowers blood glucose levels by inhibition of intestinal glucose transport

Metformin is currently the most prescribed drug for treatment of type 2 diabetes mellitus in humans. It has been well established that long-term treatment with metformin improves glucose tolerance in mice by inhibiting hepatic gluconeogenesis. Interestingly, a single dose of orally administered metformin acutely lowers blood glucose levels, however, little is known about the mechanism involved in this effect. Glucose tolerance, as assessed by the glucose tolerance test, was improved in response to prior oral metformin administration when compared to vehicle-treated mice, irrespective of whether the animals were fed either the standard or high-fat diet. Blood glucose-lowering effects of acutely administered metformin were also observed in mice lacking functional AMP-activated protein kinase, and were independent of glucagon-like-peptide-1 or N-methyl-D-aspartate receptors signaling. [18F]-FDG/PET revealed a slower intestinal transit of labeled glucose after metformin as compared to vehicle administration. Finally, metformin in a dose-dependent but indirect manner decreased glucose transport from the intestinal lumen into the blood, which was observed ex vivo as well as in vivo. Our results support the view that the inhibition of transepithelial glucose transport in the intestine is responsible for lowering blood glucose levels during an early response to oral administration of metformin.

Preliminary Results on the Use of Oral Rehydration Fluid in the Form of Gelato for Rehydration of Patients at the Children’s Clinical University Hospital’s Emergency and Infectiology Units

Oral rehydration fluids (ORS) are used to reverse dehydration that, in case of children, mostly is due to acute gastroenteritis. The key of successful dehydration treatment is to replenish the lost water and electrolytes. This is best done by consuming oral rehydration solution, containing both salt and sugar. ORS enhances fluid absorption because sodium and glucose transport in the small intestine are coupled, and glucose promotes absorption of both sodium ions and water. Studies show that children refuse ORS due to its salty-sweet taste and unpalatability. To improve oral rehydration therapy, we hypothesized that freezing ORS containing a fruit/berry juice to a likeable texture in “gelato” form could promote oral rehydration. The results provide a basis for further development of the ORS gelato with attention to flavor, sweetness and texture.

Natural Bioactive Compounds with Small-Bowel Glucose/Antiabsorption and Sugar Digestion Enzymes’ Inhibition Actions: New Strategy to Relieve Hyperglycemia and Diabetes

Intestinal glucose absorption/inhibition activity by natural bioactive compounds is considered a new strategy for prevention/treatment of uncontrolled hyperglycemia and diabetes as well as chronic human metabolic disorders. This mini review provides scientific evidence of the contribution of natural bioactive nutrients to inhibit glucose absorption in the small bowel. Many studies were realized on intestinal glucose transport in vitro and on postprandial glucose levels in vivo. In this context, the main designated constituents are (+)-catechin, (-)-epicatechin, (-)-epigallocatechin, epicatechingallate, tannic acid, resveratrol, and chlorogenic acid. The therapeutic approaches are to retard the absorption of glucose by inhibition of carbohydrate-hydrolyzing enzymes such as intestinal glycosidases (α-amylase and α-glycosidase) and the inhibition of intestinal Na+-dependent glucose absorption mediated by reduced expression of glucose transporter (SGLT1). These studies revealed that natural bioactive compounds, as potential candidates, can be designed as natural products for the development of novel functional foods or nutraceuticals to relieve hyperglycemia/diabetes.

Potato product form impacts in vitro starch digestibility and glucose transport but only modestly impacts 24 h blood glucose response in humans.

Potatoes are rich in phenolic compounds which have been reported to impact starch digestion and intestinal glucose transport in model systems through phenolic-starch interactions. While these effects are well documented for pigmented potatoes and in model systems, the relevance of phenolics to the glycemic properties of processed colorless potato-based foods under naturalistic conditions remains unclear. This study assessed impacts of processing on phenolic concentrations, resistant starch content and glycemic properties of Russet Burbank and Shepody potatoes. Product forms included French fries, shredded (hash browns) and diced (home fries) produced through commercial processing as well as parallel in-home techniques. Commercial products had significantly higher concentrations of resistant starch (p < 0.05, 1.48-6.57 vs. 1.23-2.22 g per 100 fresh weight) and resistant starch/total starch ratio (5.42-18.3% vs. 3.58-7.62%) compared to freshly prepared counterparts, while statistically lower total caffeoylquinic acid content (2.94-10.9 vs. 11.5-25.2 g per 100 fresh weight). Glucose release and intestinal transport assessed using an in vitro digestion/Caco-2 cell monolayers model demonstrated a reduction in d7-glucose intestinal transport from commercially processed products relative to fresh prepared counterparts (p < 0.05, 31.3-61.2% vs. 79.3-110% at 60 min). Commercial Russet Burbank potato products including French fries, home fries and hash browns were then selected for clinical assessment of glycemic response and appetite rating by 23 participants (11 male and 12 female). The three products presented a subtle but discernable ascending trend (French fry ≥ home fry ≥ hash browns) for incremental area under the curve (IAUC, 95.2 ± 12 vs. 105 ± 10 vs. 107 ± 14 mM min, p < 0.05) at 2 h post breakfast and for appetite rating (45.2 ± 6.3 vs. 52.4 ± 4.1 vs. 57.7 ± 7.2 for hunger) at 4 h post breakfast with no significant difference from the control (whole wheat pancake). These results suggest that potato phenolics have only a modest influence on acute glycemic responses.

Different functional roles for K+ channel subtypes in regulating small intestinal glucose and ion transport.

ABSTRACTAlthough K+ channels are important in mediating the driving force for colonic ion transport, their role in small intestinal transport is poorly understood. To investigate this, small intestinal short circuit currents (Isc) and HCO3− secretion were measured in mice, and intracellular pH (pHi) was measured in small intestinal epithelial SCBN cells. The expression and location of Kv subtypes were verified by RT-PCR, western blotting and immunohistochemistry. Diabetic mice were also used to investigate the role of Kv subtypes in regulating intestinal glucose absorption. We found that KV7.1 is not involved in duodenal ion transport, while KCa3.1 selectively regulates duodenal Isc and HCO3− secretion in a Ca2+-mediated but not cAMP-mediated manner. Blockade of KCa3.1 increased the rate of HCO3− fluxes via cystic fibrosis transmembrane conductance regulator (CFTR) channels in SCBN cells. Jejunal Isc was significantly stimulated by glucose, but markedly inhibited by 4-aminopyridine (4-AP) and tetraethylammonium (TEA). Moreover, both Kv1.1 and Kv1.3 were expressed in jejunal mucosae. Finally, 4-AP significantly attenuated weight gain of normal and diabetic mice, and both 4-AP and TEA significantly lowered blood glucose of diabetic mice. This study not only examines the contribution of various K+ channel subtypes to small intestinal epithelial ion transport and glucose absorption, but also proposes a novel concept for developing specific K+ channel blockers to reduce weight gain and lower blood glucose in diabetes mellitus.

Inhibition of intestinal glucose transport by polyphenols: a mechanism for indirect attenuation of cholesterol absorption?

Cholesterol uptake and chylomicron synthesis are promoted by increasing glucose concentrations in both healthy and diabetic individuals during the postprandial phase. The goal of this study was to test whether acute inhibition of glucose uptake could impact cholesterol absorption in differentiated human intestinal Caco-2 cells. As expected, high glucose upregulated intestinal cholesterol metabolism promoting its uptake and incorporation in lipoproteins. This was accompanied by an increase in the gene expression of Niemann-Pick C1 Like 1 and proprotein convertase subtillisin/kexin type 9. Cholesterol uptake was attenuated by acute inhibition of glucose absorption by cytochalasin B, by a chamomile extract and by one of its main constituent polyphenols, apigenin 7-O-glucoside; however, chylomicron secretion was only reduced by the chamomile extract. These data support a potential indirect role for bioactives in modulating intestinal lipid pathways through effects on intestinal glucose uptake. This working hypothesis warrants further testing in an in vivo setting such as in hypercholesterolaemic or prediabetic individuals.

Hypoglycemic potential of whole green tea: water-soluble green tea polysaccharides combined with green tea extract delays digestibility and intestinal glucose transport of rice starch.

Green tea is being studied extensively for its postprandial hypoglycemic effect due to its abundant catechins. Along with catechins, water-soluble green tea polysaccharides are also currently gaining attention due to their natural hypoglycemic properties. The current study investigated the combinational effect of green tea extract (GTE) and crude green tea polysaccharides (CTP) in inhibiting glucose transport after digestion of rice starch, using an in vitro digestion model with a Caco-2 cell. Co-digestion of rice starch with GTE (16.09 ± 1.02 g L-1), CTP (16.83 ± 0.81 g L-1), or GTE + CTP (17.79 ± 0.80 g L-1) hydrolyzed less starch into glucose compared with the control (18.24 ± 0.45 g L-1). Glucose transport from digesta to the Caco-2 cell after 120 min incubation was significantly inhibited with GTE + CTP (53.26 ± 4.34%). Gene expression of intestinal glucose transporters, which included sodium-dependent glucose transporter (SGLT1) and glucose transporter 2 (GLUT2), was not altered by GTE, CTP or GTE + CTP, except for the GTE-mediated upregulation of GLUT2. It is concluded that GTE + CTP lowered digestibility of rice starch with glucose and also delayed glucose uptake to the intestinal epithelium. This finding suggests a potential for green tea polysaccharides as a natural postprandial hypoglycemic substance.

Glucagon-Like Peptide-2 and the Enteric Nervous System Are Components of Cell-Cell Communication Pathway Regulating Intestinal Na+/Glucose Co-transport.

The Na+/glucose cotransporter 1, SGLT1 is the major route for transport of dietary glucose from the lumen of the intestine into absorptive enterocytes. Sensing of dietary sugars and artificial sweeteners by the sweet taste receptor, T1R2-T1R3, expressed in the enteroendocrine L-cell regulates SGLT1 expression in neighboring absorptive enterocytes. However, the mechanism by which sugar sensing by the enteroendocrine cell is communicated to the absorptive enterocytes is not known. Here, we show that glucagon-like peptide-2 (GLP-2) secreted from the enteroendocrine cell in response to luminal sugars regulates SGLT1 mRNA and protein expression in absorptive enterocytes, via the enteric neurons. Glucose and artificial sweeteners induced secretion of GLP-2 from mouse small intestine, which was inhibited by the sweet-taste receptor inhibitor, gurmarin. In wild type mice there was an increase in sugar-induced SGLT1 mRNA and protein abundance that was not observed in GLP-2 receptor knockout mice. GLP-2 receptor is expressed in enteric neurons, and not in absorptive enterocytes ruling out a paracrine effect of GLP-2. Electric field stimulation of the intestine resulted in upregulation of SGLT1 expression that was abolished by the nerve blocking agent tetrodotoxin. We conclude that GLP-2 and the enteric nervous system are components of the enteroendocrine-absorptive enterocyte communication pathway regulating intestinal glucose transport.

Intestinal Saturated Long-Chain Fatty Acid, Glucose and Fructose Transporters and Their Inhibition by Natural Plant Extracts in Caco-2 Cells.

The intestinal absorption of fatty acids, glucose and fructose is part of the basic requirements for the provision of energy in the body. High access of saturated long-chain fatty acids (LCFA), glucose and fructose can facilitate the development of metabolic diseases, particularly the metabolic syndrome and type-2 diabetes mellitus (T2DM). Research has been done to find substances which decelerate or inhibit intestinal resorption of these specific food components. Promising targets are the inhibition of intestinal long-chain fatty acid (FATP2, FATP4), glucose (SGLT1, GLUT2) and fructose (GLUT2, GLUT5) transporters by plant extracts and by pure substances. The largest part of active components in plant extracts belongs to the group of polyphenols. This review summarizes the knowledge about binding sites of named transporters and lists the plant extracts which were tested in Caco-2 cells regarding uptake inhibition.

Transcriptomic analysis reveals effects of fucoxanthin on intestinal glucose transport

Fucoxanthin, one of carotenoid pigments from plants and algae, is known to regulate blood glucose and insulin levels. The mechanism of its hypoglycemic activity has drawn a lot of scientific interest in recent years. In this study, we investigated the effects of fucoxanthin on intestinal glucose transport using a murine model. Our data demonstrated that fucoxanthin was able to decrease blood glucose level and alleviate insulin resistance significantly. The results from RNA-seq based transcriptomic analysis, suggested that fucoxanthin acted as a key regulator in Insulin/PI3K/AKT/mTOR signaling and PKA/AMPK/mTOR signaling pathways. Moreover, fucoxanthin ingestion resulted in a significant reduction in the protein expression of intestinal glucose transporters, such as SGLT-1, and led to decreased translocation of GLUT-2, which contributed to the regulation of blood glucose level. Together, our findings provided a mechanistic insight into the regulatory effect of fucoxanthin on blood glucose.

Intestinal Glucose Absorption Was Reduced by Vertical Sleeve Gastrectomy via Decreased Gastric Leptin Secretion.

The unique effects of gastric resection after vertical sleeve gastrectomy (VSG) on type 2 diabetes mellitus remain unclear. This work aimed to investigate the effects of VSG on gastric leptin expression and intestinal glucose absorption in high-fat diet-induced obesity. Male C57BL/6J mice were fed a high-fat diet (HFD) to induce obesity. HFD mice were randomized into VSG and sham-operation groups, and the relevant parameters were measured at 8weeks postoperation. Higher gastric leptin expression and increased intestinal glucose transport were observed in the HFD mice. Furthermore, VSG reduced gastric leptin expression and the intestinal absorption of alimentary glucose. Both exogenous leptin replenishment during the oral glucose tolerance test (OGTT) and the addition of leptin into the everted isolated jejunum loops in vitro restored the glucose transport capacity in VSG-operated mice, and this effect was abolished when the glucose transporter GLUT2 was blocked with phloretin. Moreover, phloretin almost completely suppressed glucose transport in the HFD mice. Intestinal immunohistochemistry in the obese mice showed increased GLUT2 and diminished sodium glucose co-transporter 1 (SGLT-1) in the apical membrane of enterocytes. Decreased GLUT2 and enhanced SGLT1 were observed following VSG. VSG also reduced the phosphorylation status of protein kinase C isoenzyme β II (PKCβ II) in the jejunum, which was stimulated by the combination of leptin and glucose. Our data demonstrated that the decreased secretion of gastric leptin in VSG results in a decrease in intestinal glucose absorption via modulation of GLUT2 translocation.

Front cover: In Vitro and In Vivo Inhibition of Intestinal Glucose Transport by Guava (Psidium Guajava) Extracts

Front cover: In Vitro and In Vivo Inhibition of Intestinal Glucose Transport by Guava (<i>Psidium Guajava</i>) Extracts

In Vitro and In Vivo Inhibition of Intestinal Glucose Transport by Guava (Psidium Guajava) Extracts.

ScopeKnown pharmacological activities of guava (Psidium guajava) include modulation of blood glucose levels. However, mechanistic details remain unclear in many cases.Methods and resultsThis study investigated the effects of different guava leaf and fruit extracts on intestinal glucose transport in vitro and on postprandial glucose levels in vivo. Substantial dose‐ and time‐dependent glucose transport inhibition (up to 80%) was observed for both guava fruit and leaf extracts, at conceivable physiological concentrations in Caco‐2 cells. Using sodium‐containing (both glucose transporters, sodium‐dependent glucose transporter 1 [SGLT1] and glucose transporter 2 [GLUT2], are active) and sodium‐free (only GLUT2 is active) conditions, we show that inhibition of GLUT2 was greater than that of SGLT1. Inhibitory properties of guava extracts also remained stable after digestive juice treatment, indicating a good chemical stability of the active substances. Furthermore, we could unequivocally show that guava extracts significantly reduced blood glucose levels (≈fourfold reduction) in a time‐dependent manner in vivo (C57BL/6N mice). Extracts were characterized with respect to their main putative bioactive compounds (polyphenols) using HPLC and LC‐MS.ConclusionThe data demonstrated that guava leaf and fruit extracts can potentially contribute to the regulation of blood glucose levels.

Intestinal Sodium Glucose Transporter 3 (SGLT3) is Downregulated in Experimental Models of Obesity and in Morbidly Obese Patients

Study ObjectiveImpaired regulation of intestinal glucose transporters, including sodium glucose transporter 1 (SGLT1), has been suggested to play a role in obesity‐related cardio‐metabolic pathophysiology. Although evidence indicates that SGLT3 may be involved in intestinal glucose sensing, its role in obesity is not known. Here we report that intestinal SGLT3 expression is downregulated both in experimental models of obesity and in obese patients compared with lean controls.MethodsExpression of the two Sglt3 isoforms Slc5a4a (coding Sglt3a) and Slc5a4b (coding Sglt3b) was determined in murine intestinal tissue and murine intestinal organoids using qPCR and RNAscope in‐situ hybridization. Expression of the transporters was studied in lean C57BL/6 male mice and in leptin‐deficient experimental models of obesity: C57BL/6J ob/ob−/− and Black and Tan BRachyury (BTBR) ob/ob−/− mice, with their respective lean littermates ob/ob+/? controls. To correlate experimental findings with human pathophysiology, jejunal biopsies were obtained endoscopically from lean volunteer controls and obese patients undergoing Roux‐en‐Y gastric bypass (RYGB) surgery. Furthermore, an additional biopsy was obtained from RYGB patients 6 months post‐surgery, at which time they had lost on average 29.4 % of their body weight. SGLT3 protein expression in human intestine was analyzed by western blot and immunohistochemistry.ResultsIn‐situ hybridization and qPCR revealed that Sglt3a and Sglt3b were localized in the small intestine segments (duodenum, jejunum, ileum), but not in the large intestine, in lean C57BL/6 mice. The expression of both isoforms was detected primarily in epithelial cells and this observation was confirmed in murine intestinal organoids. Furthermore, Sglt3a and Sglt3b expression was reduced in murine models of obesity. Specifically, the expression of Sglt3a and Sglt3b mRNA was significantly downregulated in duodenum and jejunum of the leptin‐deficient obesity models C57BL/6J ob/ob−/− and BTBR ob/ob−/− mice, as compared with lean littermates. In human obese patients, jejunal SGLT3 protein expression was significantly lower than in healthy lean individuals. Moreover, 6 months after RYGB weight‐loss surgery, the patients exhibited restored SGLT3 protein expression in jejunal biopsies.ConclusionWe report for the first time that SGLT3 expression is altered in experimental models of obesity and in morbidly obese patients. It is noteworthy that intestinal SGLT3 expression in obese patients was restored following weight‐loss RYGB surgery. The SGLT3 expression was mainly located in the intestinal epithelium, although further analysis is needed to decipher the specific role of SGLT3 in obesity.Support or Funding InformationThe project was funded by AstraZeneca.The Börgeson lab is supported by the Knut &amp; Alice Wallenberg Foundation, Wallenberg Centre for Molecular &amp; Translational Medicine, the Swedish Research Council, (no. 2016/82), the Swedish Society for Medical Research (no. S150086), Åke Wiberg's Foundation (no. M15‐0058), Konrad &amp; Helfrid Johansson's foundation.MS received support from Wilhelm och Martina Lundgrens foundation (no. 2017‐1850) and Sigurd and Elsa Goljes foundation (no. LA2017‐0454).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.