High Fructose Intake Research Articles

High-Fructose Diet Induces Cardiac Dysfunction via Macrophage Recruitment in Adult Mice.

Cardiovascular diseases are the leading cause of death globally, including cardiac fibrosis, myocardial infarction, cardiac hypertrophy, and heart failure. High fat/ fructose induces metabolic syndrome, hypertension and obesity, which contributes to cardiac hypertrophy and fibrosis. Excessive fructose intake accelerates inflammation in different organs and tissues, and molecular and cellular mechanisms of organ and tissue injury have been demonstrated. However, the mechanisms of cardiac inflammation have not been fully documented in high-fructose diet. This study shows that there are significantly increased in cardiomyocytes size and relative wall thickness of LV in high-fructose fed adult mice. With echocardiographic analysis of cardiac function, the ejection fraction (EF%) and fractional shortening (FS%) are significantly reduced at 12 weeks after 60% high-fructose diet. The mRNA and protein levels of MCP-1 are notably increased in high-fructose treated HL-1 and primary cardiomyocyte respectively. Also, the increased protein level of MCP-1 has been detected in vivo mouse model after 12 weeks feeding, resulting in the production of pro-inflammatory makers, pro-fibrotic genes expression, and macrophage infiltration. These data demonstrate that high-fructose intake induces cardiac inflammation via macrophage recruitment in cardiomyocyte, which contributes to impair cardiac function.

Effects of High-Fructose Corn Syrup Intake on Glucocorticoid Metabolism in Rats During Childhood, Adolescence and Adulthood.

The consumption of high-fructose corn syrup (HFCS) has been increasing in recent decades, especially among children. Some reports suggest that children and adolescents are more sensitive to the adverse effects of fructose intake than adults. However, the underlying mechanism of the difference in vulnerability between adolescence and adulthood have not yet been elucidated. In this study, we attempted to elucidate the different effects of HFCS intake at different growth stages in rats: childhood and adolescence (postnatal day (PD) 21-60), young adulthood (PD60-100), and adulthood (PD100-140). Since alterations in hepatic glucocorticoid (GC) metabolism can cause diseases including insulin resistance, we focused on GC metabolizing enzymes such as 11 beta-hydroxysteroid dehydrogenase 1 and 2 (Hsd11b1 and Hsd11b2) and steroid 5 alpha-reductase 1 (Srd5a1). Western blotting showed an increase in Hsd11b1 expression and a decrease in Hsd11b2 expression in childhood and adolescence but not in adulthood. We also observed changes in Hsd11b1 and Hsd11b2 activities only in childhood and adolescence, consistent with the results of mRNA and protein expression analysis. The effect of high-fructose intake with regards to GC metabolism may therefore vary with developmental stage. This study provides insight into the adverse effects of fructose on GC metabolism in children in the context of increasing rates of HFCS consumption.

ODP179 Development of Derivatization-free ID-LC/MS/MS Method for Simultaneous Measurement of Human Serum Monosaccharides

Abstract According to the CDC's National Diabetes Statistics Report for 2020, it is estimated that 34.2 million, 10.5% of the U. S. population, have diabetes. High fructose intake has also been associated with increased de novo lipogenesis in the liver leading to non-alcoholic fatty liver disease (NAFLD). Emerging evidence suggests that measuring fructose, galactose, and other saccharides in addition to glucose may be helpful for diagnosis of metabolic disorders and other diseases. Therefore, there is a need for an accurate and precise laboratory method for measuring serum monosaccharide panels. Traditional monosaccharide assays used in patient care often can only quantitate one monosaccharide at a time. We aim to develop a high-throughput analytical method for simultaneous measurement of serum monosaccharides that is suitable for large scale epidemiologic studies. Our assay is based on a derivatization-free ID-LC/MS/MS procedure. Certified primary reference materials of monosaccharides from NIST (Gaithersburg, MD) were used for assay calibration. The serum samples were spiked with 13 C labeled internal standards. The monosaccharides were isolated from serum matrix by acetonitrile protein precipitation and filtration in 96-well filter plate (0.2um, porous PTFE). Aliquot of the acetonitrile filtrate was applied on an AB SCIEX Triple Quad™ 6500 LC/MS/MS system for analysis. The monosaccharides including glucose, galactose, fructose, mannose, and potential interferences were resolved from each other on Unison UK Amino column (3×250mm) eluted with acetonitrile and water gradient. Selective reaction monitoring in negative electrospray ionization mode was used for quantitation of monosaccharides in the samples. The measurement ranges covered 10–402 mg/dL for glucose, which is sufficient to monitor the serum glucose levels in normal, hypo-, and hyperglycemia patient samples. Using 4 levels of NIST SRM 965b (values assigned using GC-MS based reference measurement procedure), the method demonstrated excellent measurement accuracy of over 98% for serum glucose. The imprecision of serum glucose measurement was within 3%. Imprecision and accuracy of lower abundant serum monosaccharides were lower than 6% and above 96%, respectively. The application of 96-well format filter plate and automated liquid handler system significantly improves the throughput of sample preparation. The current analytical method can be used to simultaneously measure the concentrations levels of a panel of serum monosaccharides with appropriate accuracy and precision. Free of derivatization, simple sample procedure and application of automation system significantly improves throughput of the assay which are suitable for routine serum monosaccharides assay in clinical laboratories and for large biomonitoring studies. Presentation: No date and time listed

Polydatin Ameliorates High Fructose-Induced Podocyte Oxidative Stress via Suppressing HIF-1α/NOX4 Pathway.

Long-term high fructose intake drives oxidative stress, causing glomerular podocyte injury. Polydatin, isolated from Chinese herbal medicine Polygonum cuspidatum, is used as an antioxidant agent that protects kidney function. However, it remains unclear how polydatin prevents oxidative stress-driven podocyte damage. In this study, polydatin attenuated high fructose-induced high expression of HIF-1α, inhibited NOX4-mediated stromal cell-derived factor-1α/C-X-C chemokine receptor type 4 (SDF-1α/CXCR4) axis activation, reduced reactive oxygen species (ROS) production in rat glomeruli and cultured podocytes. As a result, polydatin up-regulated nephrin and podocin, down-regulated transient receptor potential cation channel 6 (TRPC6) in these animal and cell models. Moreover, the data from HIF-1α siRNA transfection showed that high fructose increased NOX4 expression and aggravated SDF-1α/CXCR4 axis activation in an HIF-1α-dependent manner, whereas polydatin down-regulated HIF-1α to inhibit NOX4 and suppressed SDF-1α/CXCR4 axis activation, ameliorating high fructose-induced podocyte oxidative stress and injury. These findings demonstrated that high fructose-driven HIF-1α/NOX4 pathway controlled podocyte oxidative stress damage. Intervention of this disturbance by polydatin could help the development of the therapeutic strategy to combat podocyte damage associated with high fructose diet.

Negative Effects of Chronic High Intake of Fructose on Lung Diseases.

In the modern diet, excessive fructose intake (>50 g/day) had been driven by the increase, in recent decades, of the consumption of sugar-sweetened beverages. This phenomenon has dramatically increased within the Caribbean and Latin American regions. Epidemiological studies show that chronic high intake of fructose related to sugar-sweetened beverages increases the risk of developing several non-communicable diseases, such as chronic obstructive pulmonary disease and asthma, and may also contribute to the exacerbation of lung diseases, such as COVID-19. Evidence supports several mechanisms—such as dysregulation of the renin–angiotensin system, increased uric acid production, induction of aldose reductase activity, production of advanced glycation end-products, and activation of the mTORC1 pathway—that can be implicated in lung damage. This review addresses how these pathophysiologic and molecular mechanisms may explain the lung damage resulting from high intake of fructose.

Dahl Salt-Resistant Rat Is Protected against Hypertension during Diet-Induced Obesity.

A high-fat diet (HFD) frequently causes obesity-induced hypertension. Because Dahl salt-resistant rats are protected against hypertension after high-salt or high-fructose intake, it is of interest whether this model also protects against hypertension after diet-induced obesity. We tested the hypothesis that Dahl salt-resistant rat protects against hypertension during diet-induced obesity. Dahl salt-sensitive (SS) and Dahl salt-resistant (SR) rats were fed a HFD (60% fat) or a chow diet (CD; 8% fat) for 12 weeks. We measured blood pressure using the tail-cuff method. The paraffin sections of thoracic perivascular adipose tissue (tPVAT) were stained with hematoxylin/eosin and trichrome. The expression of genes in the tPVAT and kidneys were measured by reverse transcription-quantitative polymerase chain reaction. The HFD induced hypertension in SS (p < 0.01) but not SR rats, although it increased body weight gain (p < 0.05) and tPVAT weight (p < 0.01) in both rats. The HFD did not affect the expression of genes related to any of the adipocyte markers in both rats, although SR rats had reduced beige adipocyte marker Tmem26 levels (p < 0.01) and increased anti-inflammatory cytokine adiponectin (p < 0.05) as compared with SS rat. The HFD did not affect the mRNA expression of contractile factors in the tPVAT of SS and SR rats. SR rats are protected against hypertension during diet-induced obesity. This result implies that the genetic trait determining salt sensitivity may also determine fructose and fat sensitivity and that it is associated with the prevention of hypertension.

Benefits of Valsartan and Amlodipine in Lipolysis through PU.1 Inhibition in Fructose-Induced Adiposity

High fructose intake has been implicated in obesity and metabolic syndrome, which are related to increased cardiovascular mortality. However, few studies have experimentally examined the role of renin–angiotensin system blockers and calcium channel blockers (CCB) in obesity. We investigated the effects of valsartan (an angiotensin II receptor blocker) and amlodipine (a CCB) on lipolysis through the potential mechanism of PU.1 inhibition. We observed that high fructose concentrations significantly increased adipose size and triglyceride, monoacylglycerol lipase, adipose triglyceride lipase, and stearoyl-CoA desaturase-1 (SCD1), activating transcription factor 3 and PU.1 levels in adipocytes in vitro. Subsequently, PU.1 inhibitor treatment was able to reduce triglyceride, SCD1, and PU.1 levels. In addition, elevated levels of triglyceride and PU.1, stimulated by a high fructose concentration, decreased with valsartan and amlodipine treatment. Overall, these findings suggest that high fructose concentrations cause triacylglycerol storage in adipocytes through PU.1-mediated activation. Furthermore, valsartan and amlodipine treatment reduced triacylglycerol storage in adipocytes by inhibiting PU.1 activation in high fructose concentrations in vitro. Thus, the benefits of valsartan and amlodipine in lipolysis may be through PU.1 inhibition in fructose-induced adiposity, and PU.1 inhibition might have a potential therapeutic role in lipolysis in fructose-induced obesity.

Adiponectin and the expression of BAX and caspase 3 in high-fructose - induced testicular injury in albino mice

Introduction and Aim: The increase in the prevalence of obesity and metabolic syndrome in recent decades has been correlated with high consumption of high-fructose and high-fat diets and has been associated with increased rates of male infertility. The aim of this study was to investigate how high fructose diet exerts its effect upon testicular morphology in addition to examine the potential effects of adiponectin treatment in restoring the architecture of seminiferous tubules through the expression of immunohistochemical markers BAX and caspase-3. Materials and Methods: Twenty-five adult albino mice were divided into three groups: In Group 1, mice fed with diet contained high concentration of fructose followed by adiponectin injection, Group 2, the mice fed with high concentration of fructose diet and received a saline placebo injection, and Group 3 (control) was nourished a regular food for 8 weeks. The parameters studied included changes in animal body weight, testicular spermatogenesis index, spermatogonia count, apoptotic index, exfoliative epithelium percentage and immunohistochemical scores for testicular BAX and caspase-3 expression. Results: Animals on high fructose diet showed increase in body weight which was markedly reduced by adiponectin treatment. High fructose diet also resulted in reduced spermatogenesis index and spermatogonia count with increased apoptotic and epithelial exfoliation indices. High fructose diet was also associated with high-fructose induced obesity and significantly associated with increased BAX and caspase-3 expression alleviated by adiponectin treatment. Conclusion: High-fructose intake induces obesity and obesity-related reduction in male fertility by reducing spermatogenesis and enhancing testicular cell apoptosis via different pathophysiological mechanisms. Such effects and mechanism can be reversed and corrected with adiponectin treatment.

Abstract 025: RNAseq And Bioinformatics Identify New Pathways In The Thick Ascending Limb (TAL) Involved In Fructose Induced Salt Sensitive Hypertension

Elevated fructose consumption is associated with hypertension in humans. In normal Sprague Dawley rats, a high fructose intake (20% fructose drinking water) induced salt sensitive hypertension. We found that fructose directly stimulates the apical Na/K/2Cl cotransporter NKCC2 in the thick ascending limb (TAL), and when consumed for more than 7 days, increases NKCC2 phosphorylation at Thre 96,101. SPAK and OSR1 kinases are known to phosphorylate NKCC2, but it is not known how fructose activates SPAK or OSR1. We hypothesized that fructose intake activates several signaling cascades in TALs that selectively stimulate SPAK. Using an antibody that recognizes activated SPAK and OSR1 (P-Ser 373 SPAK; Ser325 in OSR1), we found that 20% fructose (14 d) enhanced SPAK/OSR1 phosphorylation by 179±32% (p&lt;0.05). This effect was specific for SPAK because phosphorylation of OSR1, immunoprecipitated from TALs, was not increased by fructose. To study the mechanism of SPAK activation, we isolated TALs from rats on control or 20% fructose diet for (14 d, n=6) and performed RNAseq. Over 12,000 genes were statistically compared and 500 were significantly different (p&lt;0.05). Expression of some of the most highly upregulated genes (PRKRIP1 and SOCS3) was confirmed by Western blot in TALs. However, expression of upstream SPAK activators was unchanged by fructose (WNK1/3/4). We developed a targeted bioinformatics approach that included angiotensin signaling, nitric oxide and lipid metabolism, plus protein-protein interaction networks for SPAK. We identified PRKCQ (PKC Theta), a kinase upstream of SPAK, that was upregulated in TALs by fructose. In fructose fed rats, PRKCQ expression was 31±11% higher than control, as was Phospho-PRKCQ (223±45% increase, p&lt;0.05). We then measured systolic BP (SBP) by telemetry in Dahl SS rats with genetic deletion of SPAK (SPAK KO). In WT Dahl SS rats, 4 weeks of fructose intake increased SBP by 25±4 mmHg (p&lt;0.05), whereas in SPAK KO the increase in SBP was reduced (11±4 mmHg, p&lt;0.05). We concluded that high fructose intake induces several prohypertensive signaling pathways in the TAL that lead to SPAK and NKCC2 activation. We identified PRKCQ as a potential activator of SPAK. Fructose induced hypertension in Dahl SS rats was in part mediated by SPAK.

Maternal fructose intake during pregnancy and lactation: Later effects on renal function.

Excessive fructose consumption has been associated with hypertension and metabolic disorders and can alter physiological adaptations during pregnancy, with long‐term detrimental consequences. This study evaluated in post‐weaning mothers the effects of increased fructose consumption during pregnancy and lactation on blood pressure and renal function. Female Wistar rats were assigned to one of four experimental groups: non‐pregnant control (NPC); pregnant control (PC); non‐pregnant fructose (NPF), and pregnant fructose (PF). Control rats had free access to food and water, while the fructose groups had free access to food and to a 20% fructose solution, over the time period of the experiment. The systolic BP and renal function parameters were measured at the end of the experimental period, one week after weaning (28 days after delivery). The results were presented as means ± standard error. Higher values of BP were observed in both pregnant and non‐pregnant rats treated with fructose compared to control. Creatinine clearance was reduced only in the PF group; however, both the PF and NPF groups had reduced Na+ and K+ excretions. In the PF group, there was also glomerular enlargement and changes in the media/lumen (M/L) ratio of interlobular arteries. Additionally, the PF group showed increased macrophage infiltration and expression of alpha‐SM‐actin and reduced expression of nitric‐oxide‐synthase endothelial in renal tissue. These findings suggest that the association of high fructose intake with pregnancy aggravated kidney changes that persisted for up to four weeks after delivery, which may represent a risk factor for maternal health.

Fructose, a trigger of metabolic diseases?—a narrative review

Worldwide the number of individuals being overweight or obese has dramatically increased during the last decades, which is also associated with a similar dramatic increase of individuals afflicted with metabolic disorders like dyslipidemia, hypertension, and non-alcoholic fatty liver disease (NAFLD). Genetic predisposition may account for some of the increases in body weight and the development of metabolic disorders; however, much is probably also related to the changes in physical activity and dietary pattern. Indeed, results of epidemiological studies suggest that a ‘western-type dietary pattern’ composed of highly processed foods, sweetened foods, and beverages, all adding to a low fiber but high sugar and saturated fat intake, may increase the odd of developing overweight and metabolic disorders. Consumption of sugar, and especially, fructose has repeatedly been discussed to be a key contributor to the development of health disturbances including hypertension, dyslipidemia, insulin resistance as well as NAFLD. However, despite intense research effort, the question if and how (high) dietary fructose intake interferes with human health has not yet been fully answered also as findings are sometimes contradictory. In the present narrative review, results of recent studies assessing the effect of fructose consumption on the development of metabolic disorders including hypertension, dyslipidemia, cardiovascular diseases (CVDs), hyperinsulinemia, and NAFLD as well as underlying molecular mechanisms are reviewed, thereby, aiming to further address the question if (high) fructose intake is a trigger of metabolic diseases.

Effect of a diet rich in galactose or fructose, with or without fructooligosaccharides, on gut microbiota composition in rats.

Recent studies suggest that a diet rich in sugars significantly affects the gut microbiota. Adverse metabolic effects of sugars may partly be mediated by alterations of gut microbiota and gut health parameters, but experimental evidence is lacking. Therefore, we investigated the effects of high intake of fructose or galactose, with/without fructooligosaccharides (FOS), on gut microbiota composition in rats and explored the association between gut microbiota and low-grade systemic inflammation. Sprague–Dawley rats (n = 6/group) were fed the following isocaloric diets for 12 weeks (% of the dry weight of the sugars or FOS): (1) starch (control), (2) fructose (50%), (3) galactose (50%), (4) starch+FOS (15%) (FOS control), (5) fructose (50%)+FOS (15%), (6) galactose (50%)+FOS (15%), and (7) starch+olive (negative control). Microbiota composition in the large intestinal content was determined by sequencing amplicons from the 16S rRNA gene; 341F and 805R primers were used to generate amplicons from the V3 and V4 regions. Actinobacteria, Verrucomicrobia, Tenericutes, and Cyanobacteria composition differed between diets. Bifidobacterium was significantly higher in all diet groups where FOS was included. Modest associations between gut microbiota and metabolic factors as well as with gut permeability markers were observed, but no associations between gut microbiota and inflammation markers were observed. We found no coherent effect of galactose or fructose on gut microbiota composition. Added FOS increased Bifidobacterium but did not mitigate potential adverse metabolic effects induced by the sugars. However, gut microbiota composition was associated with several metabolic factors and gut permeability markers which warrant further investigations.

Dahl salt-resistant rats are protected against angiotensin II-induced hypertension

Angiotensin II is a potent endogenous vasoconstrictor that induces oxidative stress in hypertensive rodent models. Dahl salt-resistant (SR) rats are protected against hypertension after high salt or high fructose intake. However, whether these rats are also protected against angiotensin II-mediated hypertension has not been investigated. Dahl salt-sensitive (SS) and SR rats were infused with angiotensin II (10 or 50 ng/kg/min) or vehicle via a mini-osmotic pump for 2 weeks. Blood pressure was measured using the tail-cuff method. Paraffin sections of the thoracic aortas and kidneys were stained using hematoxylin/eosin or Masson trichrome. Renal gene expression was measured using reverse transcription-quantitative polymerase chain reaction. Angiotensin II (50 ng/kg/min) induced hypertension in SS rats, but not in SR rats, although low doses of angiotensin II (10 ng/kg/min) transiently increased blood pressure in SS rats. Angiotensin II (50 ng/kg/min) did not induce morphological changes in the aortic walls or kidneys. Angiotensin II (50 ng/kg/min) induced the expression of At1rb, Nox2, Il-17ra, Il-23r, Tgf-β, Il-1β and Il-6 in SS rats, but not in SR rats. In conclusion, SR rats were protected against angiotensin II-induced hypertension. This result implies that the genetic trait that determines salt sensitivity may also determine susceptibility to hypertension in response to vasoconstrictors.

Metabolically associated fatty liver disease – a disease of the 21st century: A review

Metabolically associated fatty liver disease (MAFLD) is a widespread chronic disease characterized by increased accumulation of fat in the liver, which is based on metabolic dysfunction. The incidence of MAFLD is well over 20% in most regions of the world and is on an increasing trend. Current thinking considers the etiology and pathogenesis of MAFLD under the concept of "multiple parallel blows". According to this model, the development and progression of the disease are due to the interaction of multiple genetic, environmental and adaptive factors, which include specific genetic polymorphisms (e.g., the PNPLA3 gene) and epigenetic modifications, dietary patterns (e.g. high saturated fat and fructose intake), sedentary activity, obesity, insulin resistance, dysregulation of adipokines, lipotoxicity, oxidative stress, and gut microbiota dysbiosis (small intestinal bacterial overgrowth syndrome). The basis for the diagnosis of MAFLD is the presence of proven hepatic steatosis in combination with one of the following criteria: overweight/obesity, presence of type 2 diabetes mellitus, signs of metabolic dysregulation. Nonmedicamental therapies recommended for patients with MAFLD include weight loss (if overweight or obese), reduction of saturated fatty acid and fructose intake, and inclusion of adequate amounts of omega-3 polyunsaturated fatty acids and dietary fibre (psyllium) in the diet. Pharmacotherapy of MAFLD should be aimed at correcting insulin resistance, improving liver function and reducing the risk of associated diseases.

Preliminary Findings on the Effects of High Intakes of Fructose and Galactose With or Without Fructooligosaccharides on Inflammatory Markers and Blood Lipid in Rats

Abstract Objectives A high intake of sugars is associated with adverse metabolic effects in animal models and humans. However, little is known about the potential of simultaneously ingested dietary fibers to attenuate the negative effects of sugars. The current study thus aimed to investigate the effects of high intakes of fructose or galactose with or without fructooligosaccharides (FOS) on inflammation and blood lipids in rats. Methods Sprague-Dawley rats (6/group) were fed a control diet (5% fat, 35% starch) or isocaloric Western-type diets as follows: positive control (20% fat, 35% starch), fructose (20% fat, 10% starch, 25% fructose), galactose (20% fat, 10% starch, 25% galactose), FOS control (20% fat, 30% starch, 10% FOS), fructose + FOS (20% fat, 5% starch, 25% fructose, 10% FOS), and galactose + FOS (20% fat, 5% starch, 25% galactose, 10% FOS). After 8 weeks, rats were sacrificed after an overnight fast and blood and tissue samples collected and stored at −80°C until analyses. Results No differences in body weight gain, fasting blood glucose, markers of systemic (CRP, TNFα, LPS) or hepatic inflammation (TNFα), or blood lipids were observed between groups. The presence of FOS in the diets significantly reduced feed intake compared to the respective starch control group, but not compared to the isocaloric diets containing only the sugars. Conclusions These preliminary results suggest that fructose and galactose, even at high doses in the diet for 8 weeks, do not affect systemic inflammation or blood lipids in rats. Hence, no attenuating effect of the simultaneous intake of FOS could be observed. Funding Sources This project was funded by the German Federal Ministry of Education and Research within the JPI HDHL-INTIMIC 2019 program.

THIRSTY FOR FRUCTOSE: Arginine Vasopressin, Fructose, and the Pathogenesis of Metabolic and Renal Disease.

We review the pathways by which arginine vasopressin (AVP) and hydration influence the sequelae of the metabolic syndrome induced by high fructose consumption. AVP and inadequate hydration have been shown to worsen the severity of two phenotypes associated with metabolic syndrome induced by high fructose intake–enhanced lipogenesis and insulin resistance. These findings have implications for those who frequently consume sweeteners such as high fructose corn syrup (HFCS). Patients with metabolic syndrome are at higher risk for microalbuminuria and/or chronic kidney disease; however, it is difficult to discriminate the detrimental renal effects of the metabolic syndrome from those of hypertension, impaired glucose metabolism, and obesity. It is not surprising the prevalence of chronic renal insufficiency is growing hand in hand with obesity, insulin resistance, and metabolic syndrome in those who consume large amounts of fructose. Higher AVP levels and low hydration status worsen the renal insufficiency found in patients with metabolic syndrome. This inter-relationship has public health consequences, especially among underserved populations who perform physical labor in environments that place them at risk for dehydration. MesoAmerican endemic nephropathy is a type of chronic kidney disease highly prevalent in hot ambient climates from southwest Mexico through Latin America. There is growing evidence that this public health crisis is being spurred by greater fructose consumption in the face of dehydration and increased dehydration-dependent vasopressin secretion. Work is needed at unraveling the mechanism(s) by which fructose consumption and increased AVP levels can worsen the renal disease associated with components of the metabolic syndrome.

Impact of a long-term high-fructose diet on systemic metabolic profiles of mice.

Evidence is mounting that chronic high‐fructose diets (HFrD) can lead to metabolic abnormalities and cause a variety of diseases. However, the underlying mechanism by which long‐term high fructose intake influencing systemic metabolism remains unclarified. This study, therefore, attempted to investigate the impact of a high‐fructose diet on metabolic profile. Four‐week‐old male C57BL/6 mice were fed with 15% fructose solution as their only source of water for 8 weeks. Afterward, gas chromatography–mass spectrometry (GC–MS) was employed to investigate the comprehensive metabolic profile of serum, muscle, liver, heart, white adipose, brain, and kidney tissues, and multivariate analyses including principal component analysis (PCA) and orthogonal partial least squared‐discriminant analysis (OPLS‐DA) were applied to screen for differential metabolite expression between the HFrD and control groups. Furthermore, the MetaboAnalyst 5.0 (http://www.metaboanalyst.ca) and Kyoto Encyclopedia of Genes and Genomes database (KEGG; http://www.kegg.jp) were employed to portray a detailed metabolic network. This study identified 62 metabolites related to HFrD and 10 disturbed metabolic pathways. The results indicated that high fructose intake mainly influenced amino acid metabolism and biosynthesis (glycine, serine, and threonine metabolism; aspartate, and glutamate metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis, and arginine biosynthesis pathways), glutathione metabolism, sphingolipid metabolism, and glyoxylate and dicarboxylate metabolism in serum, whereas these pathways were suppressed in the brain. Starch and sucrose metabolism in muscle was also disrupted. These results elucidate the effects of long‐term high fructose consumption on the metabolic profiles of various tissues and provide new insight for the identification of potential metabolic biomarkers and pathways disrupted by high fructose.

Pharmacological Evaluation of Beta‐Hydroxifosphocarnitine in No‐Alcoholic Esteatohepatitis Induced in Rats

AimEvaluate the pharmacological effect of Β‐Hydroxyphosphocarnitine (β‐HFC) on non‐alcoholic steatohepatitis induced in rats.IntroductionNonalcoholic steatotepatitis (NASH) is a serious global public health problem, it is related to other pathologies with increasing prevalence, manifested in the increased prevalence of NASH. Type 2 diabetes mellitus and obesity are the main pathologies related to NASH. There is no specific drug for NASH, the current drugs used for NASH are related to serious side effects, which is why there is an urgent need in the development of an effective therapy for NASH but with fewer side effects. L‐carnitine has an effect on improving metabolic alterations related to NASH, however, its intestinal absorption is limited. B‐HFC is an analog of L‐carnitine that has been shown to be safe for administration, to maintain pharmacological properties of its precursor and its absorption is greater than that of L‐carnitine. So it can be a good treatment for NASH.MethodThe NASH model was developed in male Wistar rats by ingesting carbonated drink as a source of fructose, coconut oil and carbon tetrachloride. 3 groups were formed with NASH (n = 8); NASH, NASH ‐β‐HFC and NASH‐pioglitazone. Another 3 groups of healthy rats (n = 8); control, control‐β‐HFC and control‐pioglitazone. The effect of β‐HFC in rats with NASH was evaluated by staining of histological sections of liver. The stains used were Masson's trichrome, hematoxylin and osin and Periodic Acid‐Schiff (PAS). Biochemical analysis was performed to evaluate the effect of β‐HFC on the metabolic alterations that characterize NASH.ResultIt was previously reported that β‐HFC reduced the triglyceride levels of rats with NASH, as well as the levels of liver enzymes. Evidencing the effect of β‐HFC in improving lipid metabolism, manifesting itself in less liver damage. For this occasion we will report the effect of β‐HFC on liver glycogen levels. Glycogen is a reserve of the cell, as a source of glucose in prolonged fasting states. Our results demonstrated a higher glycogen reserve in the NASH rats. This result was expected, since the rats had a high fructose intake. It is important to mention that the rats with NASH but treated with β‐HFC presented reduced glycogen levels, this effect can be attributed to a more efficient β‐oxidation process, which could also justify the reduction of triglycerides and fibrosis. Therefore, we could argue that a longer treatment time, the liver alterations in NASH would improve significantly.Conclusionβ‐HFC has an effect on improving liver and metabolic alterations characteristic of the development of NASH.

Research Progress in High-Sugar Diet and Inflammatory Diseases

High-sugar diet causes various diseases, including insulin resistance, diabetes, and non-alcoholic fatty liver disease (NAFLD). In recent years, as researchers probe deeper and deeper into issues concerning high-sugar diet, the impact of high-sugar diet on inflammatory diseases such as autoimmune diseases and infectious diseases has been gradually uncovered and clarified. In this review, we summarized the current research progress on high-sugar diet and inflammatory diseases, and suggested that a high-sugar diet based on high intake of glucose and fructose may be an important factor inducing the exacerbation of chronic inflammatory diseases such as autoimmune diseases. Moreover, we also summarized the regulatory mechanisms through which high-sugar diet induces exacerbation of inflammatory diseases. In addition, we stated that conducting extensive clinical research and research in real-life settings and pursuing thorough investigation to reveal the different involvement of high-glucose diet and high-fructose diet in immune regulation are the key scientific issues that need urgent solutions in the future.

Gut microbiota depletion with antibiotics enhances fructose induced salt‐sensitive hypertension in normal rats

Introduction‐We reported that 20% fructose in drinking water induced salt‐sensitive hypertension in normal rats. High fructose (HF) or high salt (HS) intake reportedly alter the gut microbiota, which influences a variety of microbial‐regulated bioactive metabolites that can affect blood pressure and renal function. The contribution of the gut microbiota to fructose induced salt‐sensitive hypertension or renal function has not been studied. Aim‐ We hypothesized that gut microbiota depletion with antibiotics (ABX) would change fructose induced salt‐sensitive hypertension, renal excretory function and plasma levels of bacterial metabolites (lactate, β‐hydroxy‐butyrate).Methods‐Sprague Dawley rats were treated with a cocktail of antibiotics (ABX group, in g/L 1.0 ampicillin, 1.0 neomycin sulphate, 1.0 metronidazole, and 0.5 vancomycin in drinking water) for 4 weeks followed by a 0.33 fractional maintenance dose for up to 12 weeks) or control diet (no‐ABX). On week 5, all rats were given 20% fructose (HF) in drinking water and fed a diet with normal salt (NS, 0.4% Na) or high salt content (HS, 4% Na). Rats were divided as: Group 1 (HF + NS, no‐ABX, n= 6), Group 2 (HF + NS + ABX, n=6), Group 3 (HF + HS, no‐ABX, n= 8), Group 4 (HF + HS + ABX, n= 8). We trained rats and measured systolic blood pressure (SBP) for 12 weeks by tail‐cuff and collected feces before and after ABX, to measure gut c‐DNA content. On the 12th week, we collected 24‐ hour urine and plasma before the end of the protocol.Results‐ Antibiotics induced microbiome depletion (ABX) decreased fecal DNA content by 83%. Baseline SBP (in mmHg) or urine albumin excretion was not affected by ABX. Fructose with normal salt diet did not change SBP with (125±4) or without ABX (124±3). HS significantly increased SBP in rats fed fructose without ABX (from 123±3 to 141±4, p&lt;.05) but the increase was greater in ABX rats (from 124±4 to 155±3, p&lt;.05). Average increase on SBP was 26±2 in HF+HS with ABX, but only 15±2 without ABX (p&lt;.001). In HF + HS groups, ABX decreased plasma lactate from 1657±259 to 905±144 µM (p&lt;.01), and β‐hydroxy‐butyrate from 861±144 vs 220±53 µM (p&lt;.001). Non‐fasted plasma insulin was also decreased by ABX in HF+HS rats (0.77±0.13 to 0.36±0.06 ng/mL, p&lt;.03). The increase in body weight was similar in HF+HS rats with or without ABX.Conclusion‐ Chronic antibiotic treatment induced gut microbiota depletion and enhanced fructose induced salt‐sensitive hypertension in normal rats, an effect that was associated with decreased plasma beta‐hydroxy‐butyrate, lactate and insulin. Additional studies should focus on direct renal effects of ABX on salt handling.