Antidiabetic properties of polysaccharide- and polyphenolic-enriched fractions from the brown seaweed Ascophyllum nodosum

We screened seaweed species from Atlantic Canada for antidiabetic activity by testing extracts for alpha-glucosidase inhibitory effect and glucose uptake stimulatory activity. An aqueous ethanolic extract of Ascophyllum nodosum was found to be active in both assays, inhibiting rat intestinal alpha-glucosidase (IC50 = 77 microg/mL) and stimulating basal glucose uptake into 3T3-L1 adipocytes during a 20-minute incubation by about 3-fold (at 400 microg/mL extract). Bioassay-guided fractionation of the A. nodosum extract showed that alpha-glucosidase inhibition was associated with polyphenolic components in the extract. These polyphenolics, along with other constituents appeared to be responsible for the stimulatory activity on glucose uptake. However, attempts to further concentrate this activity through fractionation techniques were unsuccessful. A crude polyphenol extract (PPE), an enriched polyphenolic fraction (PPE-F1) and a polysaccharide extract (PSE) were prepared from commercial A. nodosum powder and administered to streptozotocin-diabetic mice for up to 4-weeks by daily gavage at 200 mg/kg body mass. PPE and PPE-F1 improved fasting serum glucose level in diabetic mice; however, the effect was only statistically significant at day 14. In addition, PPE-F1 was shown to blunt the rise in blood glucose after an oral sucrose tolerance test in diabetic mice. Mice treated with PPE and PPE-F1 had decreased blood total cholesterol and glycated serum protein levels compared with untreated diabetic mice, whereas PPE also normalized the reduction in liver glycogen level that occurred in diabetic animals. All 3 A. nodosum preparations improved blood antioxidant capacity.     

Antidiabetic effect of an active fraction extracted from dragon's blood (Dracaena Cochinchinensis)

The active fraction extracted from dragon's blood displayed an inhibitory effect on alpha-glucosidase activity with an IC50 of 0.152 microg/mL, which is nearly half of the crude material. Its inhibition on alpha-glucosidase was noncompetitive. In addition, when this fraction was orally administered to mice dosed with Acarbose (20 mg/kg), the active fraction (100, 300, 500 mg/kg) significantly suppressed increase of blood glucose levels after sucrose loading in a dose-dependent manner. These results suggest that this extract from dragon's blood exerts an anti-diabetic effect by suppressing intestinal carbohydrate absorption and thereby reducing the postprandial increase of blood glucose.     

Maltose metabolism of Pseudomonas fluorescens.

Pseudomonas fluorescens W uses maltose exclusively by hydrolyzing it to glucose via an inducible alpha-glucosidase (alpha-D-glucoside glucohydrolase, EC 3.2.1.20). No evidence for phosphorolytic cleavage or oxidation to maltobionic acid was found in this organism. The alpha-glucosidase was totally intracellular and was most active at pH of 7.0. Induction occurred when cells were incubated with maltotriose or maltose. Induction was rapid and easily detectable within the first 5 min after the addition of the inducer. Glucose and its derivatives did not repress induction. Cells growing on DL-alanine or succinate plus maltose exhibited lower levels of alpha-glucosidase than those grown on maltose alone or maltose plus glucose. Induction required both messenger ribonucleic acid and protein synthesis.     

Ras inhibition induces insulin sensitivity and glucose uptake

Background

Reduced glucose uptake due to insulin resistance is a pivotal mechanism in the pathogenesis of type 2 diabetes. It is also associated with increased inflammation. Ras inhibition downregulates inflammation in various experimental models. The aim of this study was to examine the effect of Ras inhibition on insulin sensitivity and glucose uptake, as well as its influence on type 2 diabetes development.

Methods and Findings

The effect of Ras inhibition on glucose uptake was examined both in vitro and in vivo. Ras was inhibited in cells transfected with a dominant-negative form of Ras or by 5-fluoro-farnesylthiosalicylic acid (F-FTS), a small-molecule Ras inhibitor. The involvement of IκB and NF-κB in Ras-inhibited glucose uptake was investigated by immunoblotting. High fat (HF)-induced diabetic mice were treated with F-FTS to test the effect of Ras inhibition on induction of hyperglycemia. Each of the Ras-inhibitory modes resulted in increased glucose uptake, whether in insulin-resistant C2C12 myotubes in vitro or in HF-induced diabetic mice in vivo. Ras inhibition also caused increased IκB expression accompanied by decreased expression of NF-κB . In fat-induced diabetic mice treated daily with F-FTS, both the incidence of hyperglycemia and the levels of serum insulin were significantly decreased.

Conclusions

Inhibition of Ras apparently induces a state of heightened insulin sensitization both in vitro and in vivo. Ras inhibition should therefore be considered as an approach worth testing for the treatment of type 2 diabetes.     

Inhibition of intestinal and renal Na+-glucose cotransporter by naringenin

Reduction in glucose uptake constitutes a possible means of controlling diabetic hyperglycemia. Using purified intestinal brush border membrane vesicles and everted intestinal sleeves, we have demonstrated that naringenin, a flavonoid present in citrus fruits and juices, significantly inhibited glucose uptake in the intestine. In addition, naringenin also elicited inhibitory actions towards glucose uptake in renal brush border membrane vesicles. Naringin, a glycoside of naringenin, was totally inactive in these aspects. Naringenin exhibited moderate inhibitory action on glucose uptake in rabbit intestinal brush border membrane vesicles, and showed strong inhibitory action in rat everted intestinal sleeves. The IC(50) values were 205.9 and 2.4 micromol/l, respectively. Lineweaver-Burk analysis demonstrated that naringenin inhibited glucose uptake in rat everted intestinal sleeves in a competitive manner with a K(i) value of 1.1 micromol/l. Glucose uptake activities in both the intestinal and renal brush border membrane vesicles of diabetic rats were significantly higher than in normal rats. Naringenin (500 microM) reduced glucose uptake by more than 60% in both the intestinal and renal brush border membrane vesicles of diabetic rats to a level similar to that of the normal rats. The IC(50) values of naringenin in the renal brush border membrane vesicles of normal and diabetic rats were 323.9 and 166.1 micromol/l, respectively. These results suggest that inhibition of intestinal glucose uptake and renal glucose reabsorption explains, in part at least, the in vivo antihyperglycemic action of naringenin and its derivatives. The possible application of these natural compounds in controlling hyperglycemia warrants further investigations.     

Kinetics of alpha-amylase synthesis from Bacillus amyloliquefaciens

The microbial production of alpha-amylase from Bacillus amyloliquefaciens was investigated. The microorganism was grown using media containing glucose or maltose at 37 degrees C and under aerobic conditions in a 16-L fermentor. The alpha-amylase synthesis from maltose was not found to be inducible but was found to be subject to catabolite repression. The maltose uptake rate was observed to be the rate-limiting step compared to the conversion rate of maltose to glucose by intracellular alpha-glucosidase. The alpha-amylase activity achieved with maltose as a substrate was higher than that achieved with glucose. A slower growth rate and a higher cell density were obtained with maltose. The enzyme production pattern depended upon the nutrient composition of the medium.     

Some properties of human liver acid alpha-glucosidase.

1. Albumin activates human liver acid alpha-glucosidase (alpha-D-glucoside hydrolase, EC 3.2.1.20). From the Arrhenius plot, pH-dependence and Lineweaver-Burk plots it can be concluded that this activation is not only due to stabilisation of the enzyme, but also influences the enzymatic activity. It is proposed that for optimal functioning human liver acid alpha-glucosidase needs a protein environment. 2. Glycogen has a competitive inhibitory effect on the hydrolysis of 4-methylumbelliferyl-alpha-D-glucopyranoside, in contrast to maltose which exhibits a non-competitive type of inhibition. It is concluded that two catalytic sites exist, one for glycogen and one for maltose, while both sites influence each other. With glycogen as substrate a break in the Arrhenius plot is found. This is not the case when maltose is used as substrate. 3. The effect of antibody raised against human liver acid alpha-glucosidase on the activity of human liver acid alpha-glucosidase is studied. No corss-reacting material could be demonstrated in the liver of a patient with glycogen storage disease Type II (M. Pompe, acid alpha-glucosidase deficiency).     

Inhibition by 2-deoxy-D-glucose of synthesis of glycoprotein enzymes by protoplasts of Saccharomyces: relation to inhibition of sugar uptake and metabolism

The synthesis of the glycoprotein enzymes, invertase and acid phosphatase, by protoplasts of Saccharomyces mutant 1016, is inhibited by 2-deoxy-d-glucose (2-dG) after a 20- to 30-min lag period under conditions (external sugar to 2-dG ratio of 40:1) which cause only a slight decrease in total protein synthesis. Formation of one intracellular enzyme, alpha-glucosidase, is also sensitive, but production of another, alkaline phosphatase, is unaffected. A nonmetabolized glucose analogue, 6-deoxy-d-glucose, had no inhibitory effect. The total uptake of external fructose and maltose was decreased by 2-dG after a lag period of about the same duration as that before the inhibition of synthesis of enzymes or of mannan and glucan; during this time 2-dG was taken up by the protoplasts and accumulated primarily as 2-dG-6-phosphate (2-dG-6-P). Studies in vitro showed that 2-dG-6-P inhibits both yeast phosphoglucose isomerase and phosphomannose isomerase. The intracellular levels of the 6-phosphates of glucose, fructose, and mannose did not increase in the presence of 2-dG. We suggest that the high internal level of 2-dG-6-P blocks synthesis of the cell wall polysaccharides and glycoproteins in two ways. It directly inhibits the conversion of fructose-6-P to glucose-6-P and to mannose-6-P. At the same time, it restricts the transport of fructose and maltose into the cell; however, the continuing limited uptake of the sugars still provides sufficient energy for protein synthesis. The cessation of alpha-glucosidase synthesis is probably a result of depletion of the internal pool of maltose (the inducer). Our findings support the suggestion that restriction of synthesis of the carbohydrate moiety of glycoproteins reduces formation of the active enzyme.     

Yeast and mammalian alpha-glucosidase inhibitory constituents from Himalayan rhubarb Rheum emodi Wall.ex Meisson

The methanolic extract of rhizome of Himalayan rhubarb Rheum emodi displayed mild yeast as well as mammalian intestinal alpha-glucosidase inhibitory activity. However, further fractionation of active extract led to the isolation of several potent molecules in excellent yields, displaying varying degrees of inhibition on two test models of alpha-glucosidase. Rhapontigenin, desoxyrhapontigenin, chrysophanol-8-O-beta-d-glucopyranoside, torachrysone-8-O-beta-d-glucopyranoside displayed potent yeast alpha-glucosidase inhibition. However chrysophanol-8-O-beta-d-glucopyranoside, desoxyrhaponticin and torachrysone-8-O-beta-d-glucopyranoside displayed potent to moderate mammalian alpha-glucosidase inhibitory activity. Other compounds displayed mild activity on both the tests. Except desoxyrhapontigenin and rhapontigenin that increased Vmax, other compounds including crude extract decreased the Vmax significantly (p<0.02) in yeast alpha-glucosidase test. Further kinetic analysis on mammalian alpha-glucosidase inhibition showed that chrysophanol-8-O-beta-d-glucopyranoside, desoxyrhaponticin and torachrysone-8-O-beta-d-glucopyranoside may be classified as mixed-noncompetitive inhibitors. However, desoxyrhapontigenin and rhapontigenin may be classified as modulators of enzyme activity. Presence and position of glycoside moiety in compounds appear important for better inhibition of mammalian alpha-glucosidase. This is the first report assigning particularly, mammalian intestinal alpha-glucosidase inhibitory activity to these compounds. Chrysophanol-8-O-beta-d-glucopyranoside, desoxyrhaponticin, desoxyrhapontigenin and rhapontigenin have been isolated in substantial yields from R. emodi for the first time. Therefore, these compounds may have value in the treatment and prevention of hyperglycemia associated diabetes mellitus.     

Caffeoylsophorose, a new natural alpha-glucosidase inhibitor, from red vinegar by fermented purple-fleshed sweet potato

The suppressive effect on the postprandial blood glucose rise through alpha-glucosidase (AGH) inhibition was investigated in this study in order to clarify an antihyperglycemic function of 6-O-caffeoylsophorose (CS) from diacylated anthocyanin. The administration of CS (100 mg/kg) following maltose (2 g/kg) to Sprague-Dawley rats resulted in the maximal blood glucose level after 30 min being significantly decreased by 11.1% compared to the control. A reduction in the serum insulin secretion was also observed in parallel to the decrease in blood glucose level. No blood glucose change was apparent when sucrose or glucose was ingested, suggesting that the antihyperglycemic effect of CS was achieved by maltase inhibition, rather than by sucrase or glucose transport inhibition. An AGH inhibitory assay demonstrated that the non-competitive maltase inhibition of CS was partly due to acylation by phenolic acid with sugar, the presence of hydroxyl groups in the aromatic ring, and the presence of an unsaturated alkyl chain in the acylated moiety.     

Suppressive effect of a hot water extract of adzuki beans (Vigna angularis) on hyperglycemia after sucrose loading in mice and diabetic rats

A hot water extract obtained by boiling adzuki beans (Vigna angularis) to produce bean paste for Japanese cake showed inhibitory activity against alpha-glucosidase, alpha-amylase, maltase, sucrase, and isomaltase after HP-20 column chromatography. The IC(50) values for each hydrolylase were 0.78 mg/ml (alpha-amylase), 2.45 mg/ml (maltase), 5.37 mg/ml (sucrase), and 1.75 mg/ml (isomaltase). The active fraction showed potential hypoglycemic activity in both normal mice and streptozotocin (STZ)-induced diabetic rats after an oral administration of sucrose, but did not show any effect on the blood glucose concentration after glucose administration, suggesting that the active fraction suppressed the postprandial blood glucose level by inhibiting alpha-glucosidase and alpha-amylase, irrespective of the endogenous blood insulin level.     

Isolation and characterization of a novel flavonoid possessing a 4,2'-glycosidic linkage from green mature acerola (Malpighia emarginata DC.) fruit

The novel flavonoid, leucocyanidin-3-O-beta-D-glucoside, possessing a 4,2'-glycosidic linkage was isolated from green mature acerola (Malpighia emarginata DC.) puree and given the trivial name "aceronidin." To examine the functions of aceronidin, its antioxidative activity and both its alpha-glucosidase and alpha-amylase inhibition activities, as a potential inhibitor of the sugar catabolic enzyme, were evaluated against those of taxifolin, catechin, isoquercitrin and quercitrin which each have a similar structure. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical quenching activity of aceronidin was stronger than that of alpha-tocopherol and comparable to that of flavonoids. In the yeast alpha-glucosidase inhibitory assay, aceronidin showed significantly greater inhibition than the other flavonoids tested. In the human salivary alpha-amylase inhibitory assay, aceronidin showed inhibition activity. Taken together, these results indicate aceronidin to be a potent antioxidant that may be valuable as an inhibitor of sugar catabolic enzymes.     

Salacia oblonga improves cardiac fibrosis and inhibits postprandial hyperglycemia in obese Zucker rats

Diabetes has a markedly greater incidence of cardiovascular disease than the non-diabetic population. The heart shows a slowly developing increase in fibrosis in diabetes. Extended cardiac fibrosis results in increased myocardial stiffness, causing ventricular dysfunction and, ultimately, heart failure. Reversal of fibrosis may improve organ function survival. Postprandial hyperglycemia plays an important role in the development of type 2 diabetes and cardiovascular complications, and has been proposed as an independent risk factor for cardiovascular diseases. Salacia oblonga (S.O.) is traditionally used in the prevention and treatment of diabetes. We investigated the effects of its water extract on cardiac fibrosis and hyperglycemia in a genetic model of type 2 diabetes, the obese Zucker rat (OZR). Chronic administration of the extract markedly improved interstitial and perivascular fibrosis in the hearts of the OZR. It also reduced plasma glucose levels in non-fasted OZR, whereas it had little effect in the fasted animals, suggesting inhibition of postprandial hyperglycemia in type 2 diabetic animals, which might play a role in improvement of the cardiac complications of OZR. Furthermore, S.O. markedly suppressed the overexpression of mRNAs encoding transforming growth factor betas 1 and 3 in the OZR heart, which may be an important part of the overall molecular mechanisms. S.O. dose-dependently inhibited the increase of plasma glucose in sucrose-, but not in glucose-loaded mice. S.O. demonstrated a strong inhibition of alpha-glucosidase activity in vitro, which is suggested to contribute to the improvement of postprandial hyperglycemia.     

Effects of castanospermine on purified lysosomal alpha-1,4-glucosidase

The indolizidine alkaloid castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine) inhibits hydrolysis of maltose, glycogen and isomaltose by purified lysosomal alpha-glucosidase yielding Ki values of 0.095, 0.10 and 0.30 mumol/l, respectively. Castanospermine exhibited high affinity for both the maltose and isomaltose sites. In distinct contrast, the alkaloid exhibited little or no affinity for the site catalyzing hydrolysis of glycogen as indicated by a noncompetitive mode of inhibition. Kinetic data presented in this report indicate castanospermine to be a very potent inhibitor of lysosomal alpha-glucosidase.     

Role of starch as a substrate for Bacteroides vulgatus growing in the human colon.

Bacteroides vulgatus is the numerically predominant Bacteroides species in the human colonic microflora. Unlike other colonic Bacteroides species, B. vulgatus is not a versatile utilizer of polysaccharides. The only types of polysaccharide that support rapid growth and high growth yields by all strains are the starches amylose and amylopectin. Amylase and alpha-glucosidase activities are among the highest found in a bacterial fraction obtained from human feces. This observation raised the question of whether B. vulgatus was the source of the fecal enzymes. Both alpha-glucosidase and amylase were produced at 20- to 40-fold-higher levels when B. vulgatus was grown on maltose, amylose, or amylopectin than when B. vulgatus was grown on glucose or other monosaccharides. Both enzymes had the same pI (4.6 to 5.0) and undenatured molecular weight (150,000). The pIs and molecular weights of the B. vulgatus amylase and alpha-glucosidase were the same as those of the fecal enzymes. To determine whether the B. vulgatus alpha-glucosidase was identical to the fecal alpha-glucosidase, we partially purified the B. vulgatus enzyme and raised an antiserum against it. Using this antiserum, we showed that all strains of B. vulgatus produced the same enzyme. The antiserum did not detect the B. vulgatus alpha-glucosidase in the bacterial fraction from human feces, even when a partially purified preparation of the fecal enzyme was used. Thus the alpha-glucosidase activity in the bacterial fraction from human feces is not the B. vulgatus enzyme.     

The maltase, glucoamylase and transglucosylase activities of acid α-glucosidase from rabbit muscle

1. The maltase and glucoamylase activities of acid alpha-glucosidase purified from rabbit muscle exhibited marked differences in certain physicochemical properties. These included pH stability, inactivation by thiol-group reagents, inhibition by alphaalpha-trehalose, methyl alpha-d-glucoside, sucrose, turanose, polyols, glucono-delta-lactone and monosaccharides, pH optimum and the kinetics and pH-dependence of cation activation. 2. The results are interpreted in terms of the existence of at least two specific substrate-binding sites or sub-sites. One site is specific for the binding of maltose and probably other oligosaccharides. The second site binds polysaccharides such as glycogen. 3. The sites appear to be in close proximity, since glycogen and maltose are mutually inhibitory substrates and interact directly in transglucosylation reactions. 4. Acid alpha-glucosidase exhibited intrinsic transglucosylase activity. The enzyme catalysed glucosyl-transfer reactions from [(14)C]maltose (donor substrate) to polysaccharides (glycogen and pullulan) and to maltose itself (disproportionation). The pH optimum was 5.1, with a shoulder or secondary activity peak at pH5.4. The glucose transferred to glycogen was attached by alpha-1,4- and alpha-1,6-linkages. Three major oligosaccharide products of enzyme action on maltose (disproportionation) were detected. 5. The kinetics of enzyme action on [(14)C]maltose showed that the rate of transglucosylation increased in a sigmoidal fashion as a function of substrate concentration, approximately in parallel with a decrease in the rate of glucose release. 6. The results are interpreted to imply competitive interaction at a specific binding site between maltose and water as glucosyl acceptors. 7. The results are discussed in terms of the possible existence of multiple subgroups of glycogen-storage disease type II.     

Role of starch as a substrate for Bacteroides vulgatus growing in the human colon

Bacteroides vulgatus is the numerically predominant Bacteroides species in the human colonic microflora. Unlike other colonic Bacteroides species, B. vulgatus is not a versatile utilizer of polysaccharides. The only types of polysaccharide that support rapid growth and high growth yields by all strains are the starches amylose and amylopectin. Amylase and alpha-glucosidase activities are among the highest found in a bacterial fraction obtained from human feces. This observation raised the question of whether B. vulgatus was the source of the fecal enzymes. Both alpha-glucosidase and amylase were produced at 20- to 40-fold-higher levels when B. vulgatus was grown on maltose, amylose, or amylopectin than when B. vulgatus was grown on glucose or other monosaccharides. Both enzymes had the same pI (4.6 to 5.0) and undenatured molecular weight (150,000). The pIs and molecular weights of the B. vulgatus amylase and alpha-glucosidase were the same as those of the fecal enzymes. To determine whether the B. vulgatus alpha-glucosidase was identical to the fecal alpha-glucosidase, we partially purified the B. vulgatus enzyme and raised an antiserum against it. Using this antiserum, we showed that all strains of B. vulgatus produced the same enzyme. The antiserum did not detect the B. vulgatus alpha-glucosidase in the bacterial fraction from human feces, even when a partially purified preparation of the fecal enzyme was used. Thus the alpha-glucosidase activity in the bacterial fraction from human feces is not the B. vulgatus enzyme.     

Misregulation of maltose uptake in a glucose repression defective mutant of Saccharomyces cerevisiae leads to glucose poisoning

In hex2 mutants of Saccharomyces cerevisiae, which are defective in glucose repression of several enzymes, growth is inhibited if maltose is present in the medium. After adding [14C]maltose to cultures growing with ethanol, maltose metabolism was followed in both hex2 mutant and wild-type cells. The amount of radioactivity incorporated was much higher in hex2 than in wild-type cells. Most of the radioactivity in hex2 cells was located in the low molecular mass fraction. Pulse-chase experiments showed that 2 h after addition of maltose, hex2 cells hydrolysed maltose to glucose, which was partially excreted into the medium. 31P-NMR studies gave evidence that turnover of sugar phosphates was completely abolished in hex2 cells after 2 h incubation with maltose. 13C-NMR spectra confirmed these results: unlike those for the wild-type, no resonances corresponding to fermentation products (ethanol, glycerol) were found for hex2 cells, whereas there were resonances corresponding to glucose. Although maltose is taken up by proton symport, the internal pH in the hex2 mutant did not change markedly during the 5 h after adding maltose. The intracellular accumulation of glucose seems to explain the inhibition of growth by maltose, probably by means of osmotic damage and/or unspecific O-glycosylation of proteins. Neither maltose permease nor maltase was over-expressed, and so these enzymes were not the cause of glucose accumulation. Hence, the coordination of maltose uptake, hydrolysis to glucose and glycolysis of glucose is not regulated simply by the specific activity of the catabolic enzymes involved.(ABSTRACT TRUNCATED AT 250 WORDS)     

Isoelectric focusing studies on the beta-fructofuranosidases and alpha-glucosidases of Streptococcus mitis.

Extracts of Streptococcus mitis ATCC 903 were analysed for beta-fructofuranosidase and alpha-glucosidase activities by isoelectric focusing in thin-layer polyacrylamide gels combined with zymogram procedures. Three bands of activity were visualized in the gels after incubation with sucrose (pI 4.05, 4.25 and 4.85) and three other bands after incubation with p-nitrophenyl alpha-D-glucopyranoside (pI 3.90, 4.45 and 4.65). The enzymes responsible for the reaction with sucrose were identified as beta-fructofuranosidases (EC 3.2.1.26) for the following reasons: identical enzyme bands were visualized in the gels after incubation with raffinose; no enzyme bands appeared in the gel after incubation with the alpha-glucosides maltose, turanose, trehalose and melezitose; and the soluble fraction hydrolysed sucrose to equimolar amounts of glucose and fructose.     

DHA and its derived lipid mediators MaR1, RvD1 and RvD2 block TNF-α inhibition of intestinal sugar and glutamine uptake in Caco-2 cells

Tumor necrosis factor-alfa (TNF-α) is a pro-inflammatory cytokine highly-involved in intestinal inflammation. Omega-3 polyunsaturated fatty acids (n3-PUFAs) show anti-inflammatory actions. We previously demonstrated that the n3-PUFA EPA prevents TNF-α inhibition of sugar uptake in Caco-2 cells. Here, we investigated whether the n3-PUFA DHA and its derived specialized pro-resolving lipid mediators (SPMs) MaR1, RvD1 and RvD2, could block TNF-α inhibition of intestinal sugar and glutamine uptake. DHA blocked TNF-α-induced inhibition of α-methyl-D-glucose (αMG) uptake and SGLT1 expression in the apical membrane of Caco-2 cells, through a pathway independent of GPR120. SPMs showed the same preventive effect but acting at concentrations 1000 times lower. In diet-induced obese (DIO) mice, oral gavage of MaR1 reversed the up-regulation of pro-inflammatory cytokines found in intestinal mucosa of these mice. However, MaR1 treatment was not able to counteract the reduced intestinal transport of αMG and SGLT1 expression in the DIO mice. In Caco-2 cells, TNF-α also inhibited glutamine uptake being this inhibition prevented by EPA, DHA and the DHA-derived SPMs. Interestingly, TNF-α increased the expression in the apical membrane of the glutamine transporter B⁰AT1. This increase was partially blocked by the n-3 PUFAs. These data reveal DHA and its SPMs as promising biomolecules to restore intestinal nutrients transport during intestinal inflammation.