Fructose aggravates copper-deficiency-induced cardiac remodeling by inhibiting SERCA2a.

OBJECTIVES: Accumulating evidence demonstrates that copper deficiency (CuD) is a risk factor for cardiovascular diseases, besides, fructose has been strongly linked to the development of cardiovascular diseases. However, how CuD or fructose causes cardiovascular diseases is not clearly delineated. The present study aims to investigate the mechanism of CuD or fructose on cardiac remodeling. METHODS: We established a model of CuD- or fructose-induced cardiac hypertrophy in 3-week-old male Sprague-Dawley (SD) rats by CuD diet supplemented with or without 30% fructose for 4 weeks. In vitro study was performed by treating cardiomyocytes with tetrathiomolydbate (TM) and fructose. Echocardiography, histology analysis, immunofluorescence, western blotting, and qPCR were performed. KEY FINDINGS: Our findings revealed that CuD caused noticeable cardiac hypertrophy either in the presence or absence of fructose supplement. Fructose exacerbated CuD-induced cardiac remodeling and intramyocardial lipid accumulation. Furthermore, we presented that the inhibition of autophagic flux caused by Ca2+ disturbance is the key mechanism by which CuD- or fructose-induced cardiac remodeling. The reduced expression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) in cardiomyocytes accounts for the elevated cytoplasmic Ca2+ concentration. CONCLUSIONS: Collectively, our study suggested that fructose aggravated CuD-induced cardiac remodeling through the blockade of autophagic flux via SERCA2a decreasing-induced Ca2+ imbalance.

Effect of Administration of Selenium Nanoparticles Synthesized Using Onion Extract on Biochemical and Inflammatory Parameters in Mice Fed with High-Fructose Diet: In Vivo and In Silico Analysis.

Fructose consumption has increased globally and has been linked to obesity, insulin resistance, and diabetes. Selenium nanoparticles (SeNPs) can regulate glucose and lipid concentrations and have immunoregulatory properties. Four study groups (n = 7/group) of eight-week-old male mice (Balb/c) were formed for this investigation. One group received a standard diet (C), another standard diet plus SeNPs (C + SeNPs), a high fructose diet (F), and a group with a high fructose diet plus SeNPs (F + SeNPs). Weight, glucose, triglycerides, and cholesterol were evaluated. In the end, mice were sacrificed, blood samples were obtained to assess cytokine profile, and liver, kidney, and pancreas were removed for histological examination. The study was complemented with an in silico analysis where the CTD, STITCH, ToppGene Suite, ShinyGO 0.76.3 databases, and Cytoscape software were implemented. The results of in vivo analysis showed that SeNPs regulated biochemical parameters and showed anti-inflammatory effects by decreasing the concentrations of TNF-alpha, IL-1beta, and IFN-gamma and increasing IL-10. No damage was observed in the studied organs. In addition, SeNPs regulate oxidative stress, preserve cell organelles, and regulate metabolic pathways to avoid the adverse effects of fructose consumption, according to bioinformatics analysis. In conclusion, SeNPs protect against the undesirable effects of a diet rich in fructose.

Protective Effect of Hydroalcoholic Extract of Punica granatum Leaves on High Fructose Induced Insulin Resistance in Experimental Animals.

BACKGROUND: Insulin resistance (IR) is a condition characterized by reduced sensitivity of body tissues to insulin, leading to impaired regulation of downstream metabolic pathways and elevated blood glucose levels. Diets rich in fructose have been proven to cause insulin resistance in test rats, resulting in decreased insulin sensitivity, particularly in the liver, and compromised disposal of glucose from the body. In the search for effective treatments, Plant-derived formulations have gained popularity because to their ability for treating a variety of ailments. One such plant is Punica granatum Linn. from the Punicaceae family, which has long been used in the treatment of diabetes and its consequences. This study investigates the insulin-resistant activity of an extract from Punica granatum leaves. The study goal is to assess the possible protective role of Punica granatum against insulin resistance through various analyses, including serum glucose and insulin levels, lipid profile assessment, measurement of liver enzymes (ALP, SGOT, SGPT), and histopathological examination of liver sections. METHODS: The study involves several key methods to evaluate the insulin-resistant activity of Punica granatum extract in high fructose diet induced insulin resistance animal model. The extract was administered orally to the experimental animals. These methods include the measurement of serum glucose and serum insulin levels, analysis of the lipid profile, quantification of liver enzymes such as ALP, SGOT, and SGPT, and a detailed histopathological examination of liver tissue sections. These analyses collectively provide insights into the impact of Punica granatum extract on insulin resistance and related metabolic parameters. RESULTS: Findings of this study provide insight on the possible benefits of Punica granatum extract on insulin resistance. Through the assessment of serum glucose and insulin levels, lipid profile analysis, and measurement of liver enzymes, the study elucidates the impact of the extract on key metabolic indicators. Additionally, the histopathological examination of liver sections provides visual insights into the structural changes that may occur as a result of the treatment. CONCLUSION: In conclusion, this study highlights the ability of Punica granatum extract as a candidate for addressing insulin resistance. The findings suggest that the extract may have a protective role against insulin resistance, as evidenced by improvements in serum glucose and insulin levels, lipid profile, liver enzyme levels, and histopathological characteristics. Further research and investigations are warranted to fully understand the mechanisms underlying these observed effects and to validate the potential of Punica granatum extract as a therapeutic option for managing insulin resistance and its associated complications.

Antioxidant Capacity of Carotenoid Extracts from the Haloarchaeon Halorhabdus utahensis.

Herein, we report on the production, characterization, and antioxidant power assessment of carotenoids from the haloarchaeon Halorhabdus utahensis. It was grown at 37 °C and 180 rpm agitation in halobacteria medium supplemented with glucose, fructose, and xylose, each at concentrations of 0.2%, 1%, and 2%, and the carotenoid yield and composition were investigated. The microorganism produced the carotenoids under all the conditions tested, and their amount followed the order glucose < xylose < fructose. The highest yield was achieved in 2% fructose growth medium with 550.60 ± 7.91 µg/g dry cell and 2428.15 ± 49.33 µg/L. Separation and identification of the carotenoids were performed by RP-HPLC and HPLC/APCI-ITMSn. Bacterioruberin was the main carotenoid detected and accounted for 60.6%, 56.4%, and 58.9% in 2% glucose, 1% xylose, and 2% fructose extracts, respectively. Several geometric isomers of bacterioruberin were distinguished, and representatives of monoanhydrobacterioruberin, and bisanhydrobacterioruberin were also detected. The assignment to cis-isomers was attempted through analysis of the UV/Vis spectra, intensity of cis peaks, and spectral fine structures. The extracts exhibited superoxide scavenging activity higher than butylhydroxytoluene, ascorbic acid, and Trolox, selected as antioxidant references. The anti-hyaluronidase capacity was investigated, and the 2% fructose extract showed the highest activity reaching 90% enzyme inhibition with 1.5 µg. The overall data confirm that Hrd. utahensis can be regarded as an interesting source of antioxidants that can find applications in the food and cosmetic sectors.

DHA, nutrient intake, and maternal characteristics as predictors of pregnancy outcomes in a randomised clinical trial of DHA supplementation.

PURPOSE: To investigate the relationships among docosahexaenoic acid (DHA) intake, nutrient intake, and maternal characteristics on pregnancy outcomes in a phase III randomised clinical trial designed to determine the effect of a DHA dose of 1000 mg/day compared to 200 mg/day on early preterm birth (<34 weeks gestation). METHODS: A secondary aim of the phase III randomised trial was to explore the relationships among pregnancy outcomes (maternal red blood cell phospholipid (RBC-PL) DHA at delivery, preterm birth, gestational age at delivery, labor type, birth anthropometric measures, low birth weight, gestational diabetes, pre-eclampsia, and admission to a neonatal intensive care unit) in participants (n = 1100). We used Bayesian multiple imputation and linear and logistic regression models to conduct an analysis of five general classes of predictor variables collected during the trial: a) DHA intake, b) nutrient intake from food and supplements, c) environmental exposure to tobacco and alcohol, d) maternal demographics, and e) maternal medical history. RESULTS: DHA supplementation lowered the risk of preterm birth and NICU admission, and increased gestation and birth weight as observed in the primary analysis. Higher maternal RBC-PL-DHA at delivery was associated with DHA supplementation and formal education of a bachelor's degree or higher. DHA supplementation and maternal age were associated with a higher risk of gestational diabetes. Total vitamin A intake was associated with longer gestation, while fructose and intake of the long chain omega-6 fatty acid, arachidonic acid, were associated with shorter gestation. Risk of preterm birth was associated with a history of low birth weight, preterm birth, pre-eclampsia, and NICU admission. CONCLUSION: Bayesian models provide a comprehensive approach to relationships among DHA intake, nutrient intake, maternal characteristics, and pregnancy outcomes. We observed previously unreported relationships between gestation duration and fructose, vitamin A, and arachidonic acid that could be the basis for future research. TRIAL REGISTRATION NUMBER AND DATE: ClinicalTrials.gov (NCT02626299); December 10, 2015.

Effects of Walnut-Rich Diet on Cation-Handling Proteins in the Heart of Healthy and Metabolically Compromised Male Rats.

The transport of cations in the cardiomyocytes, crucial for the functioning of the heart, can be affected by walnut diet due to the high content of polyunsaturated fatty acids. Healthy and metabolically compromised rats (drinking 10% fructose solution) were subjected to a diet supplemented with 2.4 g of walnuts for 6 weeks to investigate the effect on proteins involved in cation transport in the heart cells. Fructose increased the level of the α1 subunit of Na+/K+-ATPase and the phosphorylation of extracellular signal-regulated kinase 1/2 in the heart of control and walnut-eating rats, while elevated L-type calcium channel α (LTCCα), sodium-calcium exchanger 1 (NCX1), and Maxi Kα level were observed only in rats that did not consume walnuts. However, walnuts significantly increased the cardiac content of LTCC, NCX1, and Maxi Kα, as well as Kir6.1 and SUR2B subunits of KATP channel, but only in fructose-naive rats. In animals that drank fructose, a significant increasing effect of walnuts was observed only in Akt kinase phosphorylation, which may be a part of the antiarrhythmic mechanism of decreasing cation currents in cardiomyocytes. The walnut diet-induced increase in LTCC and NCX1 expression in healthy rats may indicate intense cardiac calcium turnover, whereas the effect on Kir6.1 and SUR2B subunits suggests stimulation of KATP channel transport in the cardiac vasculature. The effects of walnuts on the cation-handling proteins in the heart, mostly limited to healthy animals, suggest the possible use of a walnut-supplemented diet in the prevention rather than the treatment of cardiological channelopathies.

Silencing of Glutamine: Fructose-6-Phosphate Aminotransferase Impairs Growth and Development in Sogatella furcifera (Hemiptera: Delphacidae).

Glutamine: fructose-6-phosphate aminotransferase (GFAT), the fourth enzyme in the chitin synthesis pathway, exerts wide-ranging effects on the growth and development of organisms. However, the role of GFAT in Sogatella furcifera remains unknown. In this study, the functional significance of the GFAT gene of S. furcifera was analyzed using a reverse transcription-polymerase chain reaction and RNA interference (RNAi) analyses. The complementary DNA sequence of SfGFAT was 3162 bp in length and contained a 2067 bp open reading frame encoding 688 amino acid residues. Structural domain analysis indicated that the SfGFAT protein consisted of one glutamine aminotransferase class 2 domain and two sugar isomerase domains. Expression profile analysis revealed that SfGFAT was expressed throughout the egg, nymph, and adult phases and was strongly expressed on the first day of each nymph stage and in the integuments of five tissues. RNAi results revealed that SfGFAT gene silencing significantly inhibited the mRNA expression of the target gene and resulted in severe mortality among S. furcifera. In summary, these findings demonstrate that SfGFAT plays a critical role in the development of S. furcifera. Moreover, these results may aid in the development of methods to control the spread of S. furcifera.

The Synergistic Influence of Polyflavonoids from Citrus aurantifolia on Diabetes Treatment and Their Modulation of the PI3K/AKT/FOXO1 Signaling Pathways: Molecular Docking Analyses and In Vivo Investigations.

This study was aimed at probing the modulatory influence of polyflavonoids extracted from Citrus aurantifolia, lemon peel extract (LPE-polyflavonoids), on attenuating diabetes mellitus (DM) and its complications. HPLC investigations of the LPE exhibited the incidence of five flavonoids, including diosmin, biochanin A, hesperidin, quercetin, and hesperetin. The in silico impact on ligand-phosphatidylinositol 3-kinase (PI3K) interaction was investigated in terms of polyflavonoid class to explore the non-covalent intakes and binding affinity to the known protein active site. The drug likeness properties and pharmacokinetic parameters of the LPE-polyflavonoids were investigated to assess their bioavailability in relation to Myricetin as a control. Remarkably, the molecular docking studies demonstrated a prominent affinity score of all these agents together with PI3K, implying the potency of the extract to orchestrate PI3K, which is the predominant signal for lessening the level of blood glucose. To verify these findings, in vivo studies were conducted, utilizing diabetic male albino rats treated with LPE-polyflavonoids and other groups treated with hesperidin and diosmin as single flavonoids. Our findings demonstrated that the LPE-polyflavonoids significantly ameliorated the levels of glucose, insulin, glycogen, liver function, carbohydrate metabolizing enzymes, G6Pd, and AGEs compared to the diabetic rats and those exposed to hesperidin and diosmin. Furthermore, the LPE-polyflavonoids regulated the TBARS, GSH, CAT, TNF-α, IL-1ß, IL-6, and AFP levels in the pancreatic and hepatic tissues, suggesting their antioxidant and anti-inflammatory properties. In addition, the pancreatic and hepatic GLUT4 and GLUT2 were noticeably increased in addition to the pancreatic p-AKT in the rats administered with the LPE-polyflavonoids compared to the other diabetic rats. Remarkably, the administration of LPE-polyflavonoids upregulated the expression of the pancreatic and hepatic PI3K, AMPK, and FOXO1 genes, emphasizing the efficiency of the LPE in orchestrating all the signaling pathways necessitated to reduce the diabetes mellitus. Notably, the histopathological examinations of the pancreatic and hepatic tissues corroborated the biochemical results. Altogether, our findings accentuated the potential therapeutic role of LPE-polyflavonoids in controlling diabetes mellitus.

Pancreatic ß-Cell Apoptosis in Normoglycemic Rats is Due to Mitochondrial Translocation of p53-Induced by the Consumption of Sugar-Sweetened Beverages.

Overstimulation of pancreatic ß-cells can lead to dysfunction and death, prior to the clinical manifestations of type 2 diabetes (T2D). The excessive consumption of carbohydrates induces metabolic alterations that can affect the functions of the ß-cells and cause their death. We analyzed the role of p53 in pancreatic ß cell death in carbohydrate-supplemented Sprague Dawley rats. For four months, the animals received drinking water containing either 40% sucrose or 40% fructose. The glucose tolerance test was performed at week 15. Apoptosis was assessed with the TUNEL assay (TdT-mediated dUTP-nick end-labeling). Bax, p53, and insulin were assessed by Western blotting, immunofluorescence, and real-time quantitative PCR. Insulin, triacylglycerol, and serum glucose and fatty acids in pancreatic tissue were measured. Carbohydrate consumption promotes apoptosis and mobilization of p53 from the cytosol to rat pancreatic ß-cell mitochondria before blood glucose rises. An increase in p53, miR-34a, and Bax mRNA was also detected (P < 0.001) in the sucrose group. As well as hypertriglyceridemia, hyperinsulinemia, glucose intolerance, insulin resistance, visceral fat accumulation, and increased pancreatic fatty acids in the sucrose group. Carbohydrate consumption increases p53 and its mobilization into ß-cell mitochondria and coincides with the increased rate of apoptosis, which occurs before serum glucose levels rise.

Fructose aggravates copper-deficiency-induced non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), is the most common cause of chronic liver disease, affecting 24% of the global population. Accumulating evidence demonstrates that copper deficiency (CuD) is implicated in the development of NAFLD, besides, high fructose consumption by promoting inflammation contributes to NAFLD. However, how CuD and/or fructose (Fru) causes NAFLD is not clearly delineated. The present study aims to investigate the role of CuD and/or fructose supplement on hepatic steatosis and hepatic injury. We established a CuD rat model by feeding weaning male Sprague-Dawley rats for 4 weeks with CuD diet. Fructose was supplemented in drinking water. We found the promoting role of CuD or Fructose (Fru) in the progress of NAFLD, which was aggravated by combination of the two. Furthermore, we presented the alteration of hepatic lipid profiles (including content, composition, and saturation), especially ceramide (Cer), cardiolipin (CL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was closely associated with CuD and/or Fru fed induced-NAFLD in rat models. In conclusion, insufficient copper intake or excessive fructose supplement resulted in adverse effects on the hepatic lipid profile, and fructose supplement causes a further hepatic injury in CuD-induced NAFLD, which illuminated a better understanding of NAFLD.

Fructose supplementation shifts rat brain metabolism in experimental migraine.

AIMS: We have previously demonstrated that fructose supplementation (FS), given in a scheme used for inducing metabolic syndrome (MS), elicited pain relief in the nitroglycerin (NTG)-elicited rat migraine model. Herein, we evaluated whether FS could reestablish the impaired metabolic pathways in NTG-injected rats. MAIN METHODS: Male Wistar rats (N = 40) were divided into two groups for receiving 10 % FS or tap water. After 45 days, they were subdivided into NTG-injected (10 mg/kg; 15 days) or controls. After the fourth NTG injection, 18F-fluorodeoxyglucose ([18F] FDG) micro-PET scanning was accomplished. The day after, euthanasia was performed, and blood was collected for glycemia and LDH analysis. The levels of energy molecules, TBARS, PGC-1α, and MCTS1 were evaluated in the brain cortices. The activated satellite glial cells (SGC) were assessed in the trigeminal ganglion (TG). KEY FINDINGS: There were no variations of glycemia or LDH serum levels. NTG-injected rats showed a significant increase in glucose uptake in the hypothalamus (HT) vs. NTG-free rats. The FS-NTG group showed increased metabolism in the superior colliculus (SC) vs. the NTG group. Moreover, the glucose uptake was amplified in the inferior colliculus (IC) of the FS-NTG vs. FS group. The cortical inosine levels were significantly higher in FS-NTG rats vs. NTG or FS groups, with no changes in TBARS or MCTS1 levels, despite a minor decrease of PGC1-α contents in the FS+NTG group. Finally, there was a significant increase of activated SGC around TG in the FS-NTG rats. SIGNIFICANCE: We provide novel evidence linking nutrition and metabolism with migraine.

Effects of Fructose and Palmitic Acid on Gene Expression in Drosophila melanogaster Larvae: Implications for Neurodegenerative Diseases.

One of the largest health problems worldwide is the development of chronic noncommunicable diseases due to the consumption of hypercaloric diets. Among the most common alterations are cardiovascular diseases, and a high correlation between overnutrition and neurodegenerative diseases has also been found. The urgency in the study of specific damage to tissues such as the brain and intestine led us to use Drosophila melanogaster to study the metabolic effects caused by the consumption of fructose and palmitic acid in specific tissues. Thus, third instar larvae (96 ± 4 h) of the wild Canton-S strain of D. melanogaster were used to perform transcriptomic profiling in brain and midgut tissues to test for the potential metabolic effects of a diet supplemented with fructose and palmitic acid. Our data infer that this diet can alter the biosynthesis of proteins at the mRNA level that participate in the synthesis of amino acids, as well as fundamental enzymes for the dopaminergic and GABAergic systems in the midgut and brain. These also demonstrated alterations in the tissues of flies that may help explain the development of various reported human diseases associated with the consumption of fructose and palmitic acid in humans. These studies will not only help to better understand the mechanisms by which the consumption of these alimentary products is related to the development of neuronal diseases but may also contribute to the prevention of these conditions.

Insulin sensitization by Feronia elephantum in fructose-induced hyperinsulinemic rats: Insights from computational and experimental pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Feronia elephantum corr. (synonym: Feronia limonia, Murraya odorata, Schinus Limonia, or Limonia acidissima; common names: Bela, Kath, Billin, and Kavitha), belonging to the family Rutaceae has been known for clinical conditions such as pruritus, diarrhea, impotence, dysentery, heart diseases, and is also used as a liver tonic. However, the effect of the fruit pulp of F. elephantum on insulin resistance has yet not been reported. AIM OF THE STUDY: The present study aimed to assess the effect of hydroalcoholic extract/fraction of F. elephantum fruit pulp on fasting blood glucose, oral glucose tolerance test, and glucose uptake in fructose-induced insulin-resistant rats and predict the gene-set enrichment of lead hits of F. elephantum with targets related to insulin resistance. MATERIAL AND METHODS: System biology tools were used to predict the best category of fraction and propose a possible mechanism. Docking was carried out with adiponectin and its receptor (hub genes). Further, fructose supplementation was used for the induction of insulin resistance. Later, three doses of extract (400, 200, and 100 mg/kg) and a flavonoid-rich fraction (63 mg/kg) were used for treatment along with metformin as standard. The physical parameters like body weight, food intake, and water intake were measured along with oral glucose tolerance test, insulin tolerance test, glycogen content in skeletal muscles and liver, glucose uptake by rat hemidiaphragm, lipid profiles, anti-oxidant biomarkers, and histology of the liver and adipose tissue. RESULTS: Network pharmacology reflected the potency of F. elephantum to regulate adiponectin which may promote the reversal of insulin resistance and inhibit α-amylase and α-glucosidase. Vitexin was predicted to modulate the most genes associated with diabetes mellitus. Further, F. elephantum ameliorated the exogenous glucose clearance, promoted insulin sensitivity, reduced oxidative stress, and improved glucose and lipid metabolism. HPLC profiling revealed the presence of apigenin and quercetin in the extract for the first time. CONCLUSION: The fruit pulp of F. elephantum reverses insulin resistance by an increase in glucose uptake and a decrease in gluconeogenesis which may be due to the regulation of multiple proteins via multiple bio-actives.

The role of fructose at a range of concentration on the texture and microstructure of freeze-dried pectin-cellulose matrix cryogel.

Freeze-dried (FD) fruit and vegetable materials with a large amount of sugar are unstable. With the aim to understand the structure formation of FD products, the effects of fructose content on the texture and microstructure of FD matrix were investigated by using pectin-cellulose cryogel model. Cryogels containing fructose of 0-40% were produced using freeze-drying at three different primary drying temperatures of -40, -20, and 20°C. The resultant cryogels were characterized by texture profile analyzer, scanning electron microscope, and µCT. Results indicated that at drying temperature of -40°C, increasing fructose concentration promoted the hardness of the cryogels, and cryogels of 16% fructose obtained maximum hardness. Excessive fructose (≥20%) weakened the described hardness, while exhibiting stronger springiness and resilience. The microstructure showed that dense pores and increased wall thickness due to fructose aggregation were critical factors responsible for increased hardness. The porous structure as well as relatively large pore size were necessary for crispness, in addition, rigid pore wall with certain strength were also required. At the drying temperature of 20°C, large hetero-cavities dominated the microstructure of cryogels with 30% and 40% fructose, caused by melting inside during FD process. In this situation, lower Tm (-15.48 and -20.37°C) were responsible for cryogels' melting In conclusion, if possible, regulating fructose content and state may enable the precision texture design of FD fruit and vegetable foods.

1,5-Anhydro-D-Fructose Exhibits Satiety Effects via the Activation of Oxytocin Neurons in the Paraventricular Nucleus.

1,5-Anhydro-D-fructose (1,5-AF) is a bioactive monosaccharide that is produced by the glycogenolysis in mammalians and is metabolized to 1,5-anhydro-D-glucitol (1,5-AG). 1,5-AG is used as a marker of glycemic control in diabetes patients. 1,5-AF has a variety of physiological activities, but its effects on energy metabolism, including feeding behavior, are unclarified. The present study examined whether 1,5-AF possesses the effect of satiety. Peroral administration of 1,5-AF, and not of 1,5-AG, suppressed daily food intake. Intracerebroventricular (ICV) administration of 1,5-AF also suppressed feeding. To investigate the neurons targeted by 1,5-AF, we investigated c-Fos expression in the hypothalamus and brain stem. ICV injection of 1,5-AF significantly increased c-Fos positive oxytocin neurons and mRNA expression of oxytocin in the paraventricular nucleus (PVN). Moreover, 1,5-AF increased cytosolic Ca2+ concentration of oxytocin neurons in the PVN. Furthermore, the satiety effect of 1,5-AF was abolished in oxytocin knockout mice. These findings reveal that 1,5-AF activates PVN oxytocin neurons to suppress feeding, indicating its potential as the energy storage monitoring messenger to the hypothalamus for integrative regulation of energy metabolism.

Potential of omega-3 and conjugated fatty acids to control microglia inflammatory imbalance elicited by obesogenic nutrients.

High-fat diet-induced obesity detrimentally affects brain function by inducing chronic low-grade inflammation. This neuroinflammation is, at least in part, likely to be mediated by microglia, which are the main immune cell population in the brain. Microglia express a wide range of lipid-sensitive receptors and their activity can be modulated by fatty acids that cross the blood-brain barrier. Here, by combining live cell imaging and FRET technology we assessed how different fatty acids modulate microglia activity. We demonstrate that the combined action of fructose and palmitic acid induce Ikßα degradation and nuclear translocation of the p65 subunit nuclear factor kB (NF-κB) in HCM3 human microglia. Such obesogenic nutrients also lead to reactive oxygen species production and LynSrc activation (critical regulators of microglia inflammation). Importantly, short-time exposure to omega-3 (EPA and DHA), CLA and CLNA are sufficient to abolish NF-κB pathway activation, suggesting a potential neuroprotective role. Omega-3 and CLA also show an antioxidant potential by inhibiting reactive oxygen species production, and the activation of LynSrc in microglia. Furthermore, using chemical agonists (TUG-891) and antagonists (AH7614) of GPR120/FFA4, we demonstrated that omega-3, CLA and CLNA inhibition of the NF-κB pathway is mediated by this receptor, while omega-3 and CLA antioxidant potential occurs through different signaling mechanisms.

The Leap of Inulin Fructans from Food Industry to Medical Application.

As a dietary supplement, the efficacy of prebiotics has become a hot issue in recent years. Inulin is one of internationally recognized prebiotics and belongs to a group of non-digestible and fermentable carbohydrates. Currently, the food industry is increasingly using prebiotic inulin as a health-promoting substrate, not just as food supplement. In addition, inulin has also shown great promise in the treatment of various diseases. This article reviews the application of inulin in the food industry and summarizes physiological function of inulin. Through the review and prospect of the research on obesity, diabetes and mental illness, it provides the theoretical basis for the joint development of inulin in food industry and medical application.

Dose-Response Evaluation of Scopoletin, a Phytochemical, in a High-Fructose High-Fat Diet-Induced Dyslipidemia Model in Wistar Rats.

The putative hypolipidemic properties of scopoletin have not been fully confirmed due to a lack of validation in an irreversible chronic hyperlipidemia animal model. The druggability also needs to be studied in terms of bioavailability in the vascular compartment. Accordingly, we conducted a study to assess the hypolipidemic and pharmacokinetic behavior of scopoletin in the high-fructose high-fat diet (HFHFD)-induced dyslipidemia model in Wistar rats. A total of 42 rats were studied, with 6 in each of the 7 groups. A 60-day HFHFD opted for induction of dyslipidemia. Group I and groups II-VII received normal rat chow diet and HFHFD, respectively. Oral scopoletin (1, 5, 10 mg/kg) and atorvastatin 5 mg/kg were administered in groups III-VI, respectively, once daily for the next 15 days. A separate group, group VII, was used for the pharmacokinetic assessment comparing the scopoletin 10 mg/kg intraperitoneally (IP) in group VII versus the oral (group V). Pharmacokinetic blood sampling was performed on the 10th day of continuous once-daily therapy. Rats were sacrificed for the histological examination. All three scopoletin dosages significantly decreased the total cholesterol, low-density lipoproteins, and triglycerides (P < .05 for all), but not in a dose-dependent manner. Atherogenic Index of plasma, Castelli's risk indices, and histopathological findings confirmed the protective effect of scopoletin. The IP administration showed a 23.18% higher exposure than the oral route (P < .001 for area under the curve and P < .05 for concentration-maximum). This study confirms the hypolipidemic efficacy of scopoletin in a more robust irreversible model of dyslipidemia. Scopoletin's gut absorption in the disease state may also boost the initial phase exploratory clinical trial.

Inhibitory effect of Bofutsushosan (Fangfengtongshengsan) extract on the absorption of fructose in rats and mice.

Bofutsushosan (BTS; fangfengtongshengsan in Chinese) is a formula in traditional Japanese Kampo and Chinese medicine comprising 18 crude drugs and used to treat obesity and metabolic syndrome. In our previous study, BTS boiling water extract inhibited the uptake of fructose absorbed via glucose transporter 5 into cultured cells. In this study, the inhibitory effect of BTS extract on the absorption of fructose from the intestine was investigated in vivo. The extract of BTS was orally administered to rats at doses equivalent to 25-fold of the daily dose for humans. One minute after sample administration, fructose was orally administered and blood samples were collected from the jugular vein 0.5, 1, 1.5, 2, and 4 h after the administration of fructose. The absorption of fructose from the intestine was significantly reduced by treatment with BTS extract, and this in vivo study reproduced previous in vitro results. Subsequently, the blood samples were collected from the portal vein 30 min after the oral administration of fructose in mice. BTS extract significantly reduced fructose absorption in mice, and compared the effect of modified BTS samples by removing one to several crude drugs from BTS. We found that the dried rhizome of Rheum palmatum (RR) significantly contributed to the inhibitory effect of BTS on fructose absorption. We found sennoside A to be the active ingredient of RR for the inhibition of fructose absorption, and that its effect almost saturated at a dose of 3 mg/kg. These results support the action mechanisms of BTS when used for the treatment of obesity in clinics and drug stores.