Search Results (238)

Background/Objectives: Exposure to high and sustained levels of non-esterified fatty acids (NEFA) in the peripartal period is the main cause of fatty liver disease in dairy cows. Rumen-protected choline is often fed as part of the nutritional management of peripartal cows, with in vivo and in vitro data indicating positive effects of this nutrient on alleviating liver lipid accumulation. Although hepatic molecular mechanisms associated with choline supply have been studied using a target gene, protein, or metabolite approach, application of high-throughput technologies could vastly enhance fundamental knowledge on the functional role of choline. The main objective was to challenge isolated hepatocytes with a mixture of NEFA and determine proteome- and metabolome-wide effects in response to choline supply. Methods: Three healthy female calves (1 d old, 30–45 kg) were sacrificed to harvest hepatocytes. During a 12 h incubation, isolated hepatocytes were challenged without NEFA (control), 1.2 mM NEFA (c9-18:1, 18:2, 16:0, 18:0, and c9-16:1 at 43.5%, 4.9%, 31.9%, 14.4%, and 5.3% of total NEFA, respectively), or NEFA for 6 h followed by 10 μM choline chloride for another 6 h (NEFA + Chol). iTRAQ labeling-based protein profiling and GC/MS-based metabolomics profiling were used to determine changes in proteins and metabolites. Differentially abundant proteins for each group comparison were determined at a threshold of 1.4-fold change. Differences in metabolite profiles were assessed via pairwise comparisons. A subset of differentially abundant proteins was validated via qRT-PCR and Western blotting. Results: Compared with the control, there were 90 proteins and 22 metabolites in the NEFA group, and 83 proteins and 29 metabolites in the NEFA + Chol. Compared with NEFA, there were 49 proteins and 17 metabolites in the NEFA + Chol group. Greater abundance of hexokinase-1 (HK1), fructose-bisphosphate aldolase (ALDOA), mitochondrial pyruvate carrier 1 (MPC1), and increased concentrations of lactate with high NEFA treatment alone suggested greater glycolytic and TCA cycle activity. Accumulation of triacylglycerol in the NEFA group was associated with lipotoxicity and markers of inflammation, such as greater abundance of prostaglandin reductase 1 (PTGR1), serious cell autophagy processes, such as greater abundance of cell division cycle 42 (CDC42), and NFκB-related proteins. Choline supplementation reduced TAG partly due to greater VLDL secretion driven by greater abundance of diacylglycerol acyltransferase (DGAT1), perilipin 3 (PLIN3), and apolipoprotein C-III (APOC3). In addition, a greater abundance of carnitine O-palmitoyltransferase 1b (CPT1B) with choline suggested enhanced mitochondrial β-oxidation. Activation of the CDC42/JNK pathway and ROS/NFκB axis-related proteins, along with depressed PI3K/AKT/RAC-related proteins, indicated enhanced mitochondrial autophagy in response to NEFA. Conclusions: Overall, data confirmed published effects of choline on TAG accumulation, VLDL secretion, and fatty acid oxidation, while highlighting negative effects of NEFA on the respiratory electron transport chain, autophagy, and inflammatory processes. Full article

Plants can provide natural enemies with alternative food resources that enhance their performance in addition to prey consumption. Extrafloral nectaries attract beneficial insects by supplying nectar in exchange for pest suppression, although other arthropods may also benefit. This study aimed to characterize the extrafloral nectar composition of bottle gourd, Lagenaria siceraria (Molina) Standley (Cucurbitaceae), a host plant of Nesidiocoris tenuis Reuter (Hemiptera: Miridae), and to evaluate the effects of its carbohydrate profile on key biological parameters of this predator. Extrafloral nectar was chemically characterized for carbohydrate and amino acid composition, and laboratory bioassays were conducted to assess the effects of a sugar solution of the extrafloral nectar carbohydrate profile when provided with two factitious food sources, Ephestia kuehniella Zeller (Lepidoptera: Pyralidae) eggs and Artemia sp. (Anostraca: Artemiidae) cysts. Female egg production, nymphal development and food source consumption were evaluated. Chemical analysis revealed that bottle gourd extrafloral nectar consisted primarily of glucose, fructose, sucrose and melezitose, while serine was the dominant amino acid. Four essential amino acids were also detected. Sugar supplementation did not affect nymphal development rate but significantly reduced factitious food consumption. Significant differences in egg production were observed among feeding regimes. Sugar supplementation did not affect egg production when E. kuehniella eggs were provided, but significantly increased egg production when Artemia cysts were used as food source. These results indicate that extrafloral nectar carbohydrates can function as effective supplementary nutritional resources for N. tenuis, particularly when lower-quality factitious food sources are used. These findings enhance our understanding of plant–predator nutritional interactions and suggest that extrafloral nectar-derived components warrant further evaluation for incorporation into mass rearing protocols. Full article

Fructose, a key component of modern diets, is closely linked to the growing prevalence of pediatric obesity and metabolic alterations. Although numerous studies highlight its systemic consequences, including altered carbohydrate and lipid metabolism and increased cardiovascular risk, the direct impact of fructose, particularly its role in modulating mucin composition, a key determinant of the mucosal barrier, remains poorly explored. This study investigated whether fructose supplementation modifies high-fat diet (HFD)-induced changes in duodenal mucin production and whether these effects vary depending on age in animals. To this end, young and adult mice were fed a normal diet (ND), HFD, or an HFD supplemented with 30% fructose (w/v) in drinking water (HFD+Fru) for 16 weeks. Brunner’s glands and villus goblet cells were then analyzed using conventional histochemistry and a panel of lectins to evaluate possible alterations in intestinal mucus glycosylation. Results showed that both HFD and HFD+Fru significantly increased body weight. In young mice, HFD+Fru induced a compensatory mucosal phenotype characterized by increased villus PAS (Periodic Acid–Schiff) reactivity (2% vs. ND), elevated sialylated mucin secretion rate (SSR) in Brunner’s glands (25% vs. ND) and villi (17% vs. ND), and higher SNA (up to 46% vs. ND) and PNA (up to 39% vs. ND) in villus goblet cells. In contrast, adult mice receiving HFD+Fru exhibited a maladaptive response, characterized by a reduction in villus PAS-positive mucins (6% vs. ND), decreased villus SSR (5% vs. ND), diminished sialylation (up to 43% SNA vs. ND) and GlcNAc (up to 50% reduction in WGA vs. ND) in villus goblet cells, and marked loss of fucosylation in Brunner’s glands (81% vs. ND) and villus goblet cells (66% vs. ND). These results reveal that fructose-enriched HFD remodels duodenal mucin O-glycosylation in an age-dependent manner, suggesting that while young mice exhibit transient adaptive responses, prolonged exposure can deplete these mechanisms, leading to a compromised adult epithelial barrier. This age-specific vulnerability may significantly contribute to the pathogenesis of diet-related intestinal disorders and obesity-related complications in later life, highlighting the need for early dietary interventions. Full article

Prediabetes is increasingly recognized as a risk factor for sarcopenia, driven by chronic low-grade inflammation, insulin resistance, and impaired anabolic signaling. Nutritional interventions containing whey protein, hydroxymethylbutyrate (HMB), glucosamine, and micronutrients may offer a multi-target strategy to counteract muscle deterioration. This study aimed to evaluate the efficacy of HiLo Platinum™ supplementation in attenuating muscle strength decline in a prediabetic rat model, with integrated analysis of metabolic biomarkers and gut microbiome profiles. A randomized preclinical trial was conducted using male Sprague Dawley rats assigned to four groups: normal diet (ND), prediabetic control induced by cholesterol- and fat-enriched diet with fructose (CFEDF), and two treatment groups receiving low-dose (0.63 g/kg BW) or high-dose (1.26 g/kg BW) HiLo Platinum™. The intervention lasted six weeks. Muscle strength was assessed via a four-limb grip strength test (reverse hang time and holding impulse). Biomarkers related to inflammation, mitochondrial function, and anabolic signaling (TNF-α, IL-10, PGC-1α, IGF-1, SIRT-1, AMPK, mTOR, and myostatin), lipid profile, and blood glucose were analyzed. Gut microbiome composition and diversity were evaluated using taxonomic profiling and multivariate analyses. HiLo Platinum™ supplementation significantly improved muscle strength, evidenced by increased reverse hang time and holding impulse (p < 0.001). Both doses reduced blood glucose and improved lipid profiles, including increased HDL and decreased LDL, triglycerides, and total cholesterol. Anti-inflammatory effects were observed with reduced TNF-α and elevated IL-10 levels. Mitochondrial and metabolic regulators (PGC-1α, SIRT-1, AMPK) and anabolic mediators (IGF-1) were significantly upregulated, while mTOR levels decreased. Gut microbiome analysis revealed increased genus richness (Chao1 index) and distinct microbial shifts associated with improved metabolic and inflammatory markers. HiLo Platinum™ effectively mitigates prediabetes-induced muscle strength decline through integrated modulation of inflammatory pathways, mitochondrial function, metabolic homeostasis, and gut microbiome composition. These findings support its potential as a nutritional therapeutic strategy for preventing sarcopenia in prediabetic conditions, although further studies are needed to evaluate long-term effects and implications on muscle hypertrophy. Full article

Roselle beverage residue (RBR), a by-product of Hibiscus sabdariffa L. processing, retains bioactive compounds, including soluble and insoluble dietary fiber and polyphenols. Its antihyperglycemic effect in type 2 diabetes mellitus (T2DM) has been previously demonstrated; however, its role in lipid metabolism remains unknown. This study assessed the preventive and therapeutic potential of RBR on dyslipidemia and hepatic steatosis in a rodent model of late-stage T2DM characterized by hyperglycemia and hypoinsulinemia. Male Wistar rats with T2DM induced by a high-fat and high-fructose diet combined with streptozotocin received 6% RBR supplementation as either a preventive intervention (starting at week 1 in healthy rats or week 9 in insulin-resistant rats) or a therapeutic intervention (starting at week 14 in diabetic rats). After 17 weeks, RBR supplementation significantly reduced serum triglycerides and total cholesterol, attenuating hepatic lipid accumulation regardless of the timing of intervention. Hepatic Acadm expression, involved in fatty acid β-oxidation, was significantly upregulated in rats treated with RBR from week 1 and 9, whereas no significant modulation was observed for genes related to fatty acid synthesis or uptake. These findings suggest that RBR supplementation may contribute to improving lipid metabolism and hepatic steatosis in a rat model of late-stage T2DM. Full article

The roles of light and carbohydrates in adventitious root formation of Hydrangea macrophylla cuttings of the cultivars ‘Caipirinha’ and ‘Clarissa’ were investigated. Cuttings were planted immediately or dark-stored for seven days prior to cultivation under light. The leaf and rooting phenotype, relative chlorophyll content, carbohydrate levels in different cutting sections and rooting response to hexose were analyzed. Surprisingly, pronounced leaf yellowing and reddening and a strong hexose accumulation in the cutting leaves indicated that the hydrangea cuttings experienced light stress under a photosynthetic photon flux density (PPFD) of 100 µmol m⁻² s⁻¹. Reduction in PPFD to 50 µmol m⁻² s⁻¹ decreased these symptoms and increased chlorophyll content, but impaired rooting. The effects of dark storage depended on cultivar, PPFD, and hydration of cuttings. ‘Clarissa’ exhibited lower rooting success, particularly after dark storage and low light, and showed lower hexose-to-sucrose ratios and hexose concentrations in the stem base than ‘Caipirinha’. Rooting of ‘Clarissa’ could not be rescued by sugar supplementation, whereas application of 27 mM glucose plus 30 mM fructose for 24 h before planting enhanced rooting of ‘Caipirinha’. The lower hexose level in the stem base of ‘Clarissa’ does not appear to be the critical factor underlying its low rooting capacity. Full article

Sclerodermus guani Xiao et Wu, 1983 plays a significant role in the biological control of agricultural and forestry pests. To investigate whether different sugar types significantly affect the longevity, fecundity, and nutrient reserves of female S. guani adults, this study provided 1 mol/L solutions of sucrose, fructose, glucose, mannose, or trehalose under laboratory conditions, with a distilled water group serving as the control. The longevity and nutrient content of parasitoids were measured after varying feeding durations, while fecundity was assessed in preliminary experiments. The results demonstrated that prolonged sugar feeding significantly extended parasitoid longevity, with fructose, glucose, and sucrose exhibiting the most pronounced effects and no significant differences among them. Nutrient analysis revealed that sugar consumption significantly increased total carbohydrate content, slowed lipid depletion, and promoted protein accumulation. Sucrose, fructose, and glucose outperformed other sugars and the control in these aspects. Fecundity assays indicated that glucose and trehalose significantly shortened the pre-oviposition period and enhanced egg production. In conclusion, nutritional supplementation markedly improves the longevity and reproductive performance of S. guani, with 1 mol/L glucose identified as the optimal dietary source. Full article

This study focused on optimizing endoglucanase production using a peculiar fungal co-culture comprising Rhizopus arrhizus and Aspergillus fumigatus, identified through morphological and 18S rDNA analyses. The co-culture achieved the highest enzyme production after 72 h of fermentation with alkaline-treated substrates. Scanning Electron Microscopy (SEM) revealed substantial structural disruption in pretreated biomass, enhancing enzyme accessibility. Among the tested substrates, pea hulls proved to be the most effective for enzyme production. Optimization of physical and nutritional parameters was performed using Design of Experiments (DOE) approaches, specifically Plackett–Burman Design (PBD) for screening and Central Composite Design (CCD) for fine optimization. The maximum endoglucanase activity of 119.58 U/mL/min was obtained under the optimized conditions of 27.5 °C, pH 5.5, inoculum age 3.5 days, and supplementation with 1.5% fructose, 1.25% yeast extract, 1.25% sodium nitrate, and 1.25% Tween 80. Analysis of Variance (ANOVA) confirmed the significance of these parameters and their interactions at a 95% confidence level, with a strong model fit (R² = 0.9052). This study demonstrates the potential of waste pea hulls as a cost-effective substrate for enzyme production, supporting waste valorization and contributing to a circular bioeconomy through sustainable biomass utilization. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease worldwide. Fibrosis is the main prognostic factor and the last reversible stage before cirrhosis, yet therapeutic options remain limited. Given the strong contribution of gut dysbiosis to MASLD progression, strategies targeting the gut microbiota are of growing interest. This study aims to evaluate the effect of melatonin, a well-known antioxidant, anti-inflammatory and antifibrotic compound, and Akkermansia muciniphila, a next-generation probiotic, on an MASLD-associated liver fibrosis model. Eight-week-old C57BL/6J mice were fed a control or Western diet supplemented with fructose and intraperitoneal CCl₄ to induce liver fibrosis. After eight weeks, the animals received either no intervention, melatonin, A. muciniphila, or both for four weeks. Serum biochemistry, liver histology and gut and liver gene expression were evaluated and multi-omic analyses were performed, including gut microbiota profiling and faecal metabolomics. Statistical analyses assessed intergroup differences and correlations across datasets. Both interventions partially restored gut microbiota composition and functionality and modulated hepatic and intestinal gene expression. Melatonin and A. muciniphila exerted protective effects against MASLD-associated fibrosis, which supports their potential as adjunctive therapeutic strategies to mitigate liver injury through modulation of the gut–liver axis. Full article

Background: Fructans are fructose-based polysaccharides with diverse biological activities; however, their direct activity on skin cells remains unresolved. This study investigated the biological activity of fructan extracted from rakkyo (Allium chinense) (RF) and examined its effects on extracellular matrix (ECM) metabolism, particularly collagen and hyaluronan synthesis, in human dermal fibroblasts. Methods: RF was prepared from fresh rakkyo bulbs by aqueous extraction, alkaline clarification, and membrane filtration. The average molecular weight and structural characteristics of RF were analyzed using size-exclusion chromatography and ¹³C NMR spectroscopy. Normal human dermal fibroblasts (NHDFs) were treated with RF by culturing cells in RF-supplemented medium (0.1–1.0 mg/mL). Cell viability and viable cell number were evaluated using the thiazolyl blue tetrazolium bromide and trypan blue exclusion assays, respectively. Expression of ECM-related genes was analyzed by qRT-PCR, and collagen and hyaluronan production were quantified by Sirius Red staining and ELISA. Results: RF had an average molecular weight of approximately 11,500 Da and consisted of nearly equal proportions of inulin- and levan-type fructans. RF (≤1 mg/mL) increased the number of viable cells and markedly upregulated collagen, type I, alpha 1 (COL1A1) and hyaluronic acid synthase 2 (HAS2) expression while downregulating Hyal1 expression. After 9 days of treatment, the cumulative production of type I collagen and hyaluronic acid increased by 3.8- and 1.3-fold, respectively, as compared with controls. Upregulation of lysyl oxidase (LOX) mRNA suggested enhanced collagen cross-linking, whereas MMP-1 showed only modest induction. Conclusions: Rakkyo-derived fructan directly stimulates collagen and hyaluronan synthesis in dermal fibroblasts, likely through regulation of ECM-related genes. These results suggest that rakkyo-derived fructan modulates ECM-related readouts in NHDFs under controlled in vitro conditions. Further validation in more complex skin models and in vivo studies is necessary. Full article

Precision nutrition has emerged as a promising strategy for the prevention of type 2 diabetes mellitus (T2DM) by targeting molecular pathways underlying insulin resistance and impaired glucose metabolism. Accumulating evidence indicates that dietary patterns, caloric intake, and specific nutrients can modulate gene expression and epigenetic mechanisms involved in insulin signaling, inflammation, and energy homeostasis. This narrative review synthesizes recent human and experimental studies (2025–2026) examining how dietary components influence transcriptional and epigenetic regulation of insulin signaling and glucose metabolism in the context of T2DM prevention. A total of 29 peer-reviewed studies were included, encompassing dietary patterns, macronutrient manipulation, micronutrient and bioactive supplementation, and gene–diet interactions. Very-low-calorie diets consistently induced coordinated modulation of key metabolic genes, including downregulation of glucose transporter type 4 (GLUT4) and upregulation of PDK4, CPT1, and AMPK, reflecting a metabolic shift toward enhanced fatty acid oxidation and improved insulin sensitivity. In contrast, high-fat and fructose-rich diets promoted proinflammatory gene expression and immune activation, contributing to insulin resistance. Plant-based and vegan dietary patterns were associated with reduced epigenetic aging and improved insulin sensitivity through DNA methylation changes. Targeted interventions, including vitamin D combined with probiotics, dietary fiber, nucleotides, and trace elements such as copper, further demonstrated favorable transcriptional and epigenetic effects linked to improved glycemic control. Collectively, these findings highlight diet-driven modulation of insulin signaling and glucose metabolism at the molecular level and support nutrigenomics-guided precision nutrition as a viable preventive approach for T2DM. Integrating genetic and epigenetic insights into dietary strategies may enable more personalized and effective interventions to curb the growing global burden of type 2 diabetes. Full article

Soil salinization and alkalinization critically constrain alfalfa (Medicago sativa L.) productivity, yet the regulatory mechanisms underlying its responses to salt–alkali stress are not fully understood. In this study, the alfalfa variety “Zhongmu No. 1” was used as experimental material. The seeds were subjected to salt stress (75 mM NaCl), alkali stress (15 mM NaHCO₃), and combined salt–alkali stress (50 mM NaCl + 5 mM NaHCO₃) in dishes, with ddH₂O serving as the control (CK). After 7 days of germination, the seedlings were transferred to a hydroponic system containing Hoagland nutrient solution supplemented with the corresponding treatments. Following 32 days of stress exposure, leaf and root tissue samples were collected for morphological and physiological measurements, as well as mRNA and miRNA sequencing analyses. Physiological assays revealed significant growth inhibition and increased electrolyte leakage under stress conditions. Transcriptome profiling identified over 5000 common differentially expressed genes (DEGs) in both leaves and roots under stress conditions, mainly enriched in pathways related to “iron ion binding”, “flavonoid biosynthesis”, “MAPK signaling”, and “alpha-Linolenic acid metabolism”. MiRNA sequencing detected 453 miRNAs, including 188 novel candidates, with several differentially expressed miRNAs (DEMs) exhibiting tissue- and stress-specific patterns. Integrated analysis revealed 147, 81, and 140 negatively correlated miRNA–mRNA pairs across three treatment groups, highlighting key regulatory modules in hormone signaling and metabolic pathways. Notably, in the ethylene and abscisic acid signaling pathways, ERF (XLOC_006645) and PP2C (MsG0180000476.01) were found to be regulated by miR5255 and miR172c, respectively, suggesting a post-transcriptional layer of hormonal control. DEM target genes enrichment pathway analyses also identified stress-specific regulation of “Fatty acid degradation”, “Galactose metabolism”, and “Fructose and mannose metabolism”. qRT-PCR validation confirmed the expression trends of selected DEGs and DEMs. Collectively, these findings reveal the complexity of miRNA–mRNA regulatory networks in alfalfa’s response to salt–alkali stress and provide candidate regulators for breeding stress-resilient cultivars. Full article

Background/Objectives: Metabolic-dysfunction-associated fatty liver disease (MASLD) is characterised by an excessive hepatic lipid accumulation. The present research aims to study the impact of an Opuntia stricta var. dillenii peel extract and an Opuntia ficus-indica var. colorada pulp extract, known for their high content of betalains and phenolic compounds, on the prevention of hepatic lipid accumulation in the liver of rats with steatosis. Methods: For this, MASLD was induced in 60 male Wistar rats by a high-fat high-fructose diet. They were supplemented with Opuntia stricta var. dillenii peel extract or Opuntia ficus-indica var. colorada pulp extract at 25 or 100 mg/kg body weight/d. Results: The high-fat high-fructose diet caused an increase in final body and liver weight, hepatic triglyceride (TG) content, and altered liver histology. The increase in hepatic TG was due to the rise in fatty acid uptake and the increased assembly of TG, although increased de novo lipogenesis cannot be ruled out. The treatment with a low dose of Opuntia ficus-indica var. colorada pulp extract (L-OFI group) significantly prevented hepatic TG accumulation, and the high dose (H-OFI group) showed a tendency towards lower values compared to the rats fed the high-fat high-fructose diet. The main mechanism of action appears to be a down-regulation of fatty acid uptake. By contrast, Opuntia stricta var. dillenii peel extract did not prevent the high-fat high-fructose diet-induced steatosis. Conclusions: Overall, Opuntia ficus-indica var. colorada pulp extract may represent a potential strategy for MASLD prevention, although its beneficial effects require confirmation in human studies. Full article

Background: Unhealthy diets characterized by high salt, fat, and fructose content are established risk factors for metabolic and cardiovascular disorders and may have indirect effects on cognitive function. However, the combined impact of a high-salt, high-fat, and high-fructose diet (HSHFHFD) on systemic physiology and brain health remains to be fully elucidated. Methods: Sprague-Dawley (SD) rats received a customized high-salt, high-fat diet supplemented with 30% fructose water for 18 weeks. Physiological and brain parameters were assessed, in combination with multi-omics analyses including brain proteomics and metabolomics, serum metabolomics, and gut microbiota profiling. Results: HSHFHFD significantly elevated blood glucose, blood pressure, and serum levels of TG, TC, and LDL in rats. Serum metabolomic profiling identified over 100 differentially abundant metabolites in the Model group. Proteomics, metabolomics, and gut microbiome integration revealed pronounced alterations in both brain proteomic and metabolomic profiles, with 155 differentially expressed proteins associated with glial cell proliferation and 65 differential metabolites linked to fatty acid and amino acid metabolism, among others. Experimental validation confirmed marked upregulation of GFAP and Bax protein, concomitant with downregulation of ZO-1 and occludin. Furthermore, HSHFHFD perturbed the CREB signaling pathway, leading to diminished BDNF expression. The levels of inflammatory factors, including IL-6, IL-10, IL-1β and TNFα, were significantly elevated in the brain. Oxidative stress was evident, as indicated by elevated malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) activity, and altered NAD⁺/NADH ratio. Additionally, HSHFHFD significantly reduced the abundance of beneficial gut bacteria, including Lactobacillus, Romboutsia, and Monoglobus. Conclusions: HSHFHFD-induced depletion of gut Lactobacillus spp. may disrupt the linoleic acid metabolic pathway and gut–brain axis homeostasis, leading to the impairment of neuroprotective function, blood–brain barrier dysfunction, and exacerbated neuroinflammation and oxidative stress in the brain. These effects potentially increase the susceptibility of rats to neurodegenerative disorders. Full article

Dietary pattern characterized by low intake of vegetables and fruits and high consumption of fat, soft drink and desserts are associated with an increased risk of chronic diseases. To investigate the effects of folate status and fructose intake on adenine-induced chronic kidney disease (CKD), seven-week-old C57BL/6 mice were divided into six groups and fed either a control diet (Ctrl), a 26% (w/w) high-fructose diet (Hfru), Ctrl plus 0.15% adenine (Ctrl+ade), Hfru+ade, Hfru with folate deficiency plus adenine (Hfru−f+ade), or Hfru with tenfold folate supplementation plus adenine (Hfru+f10+ade). After 10 weeks on the assigned diets, adenine was administrated to the +ade groups for 7 weeks. The results showed that all adenine-treated mice exhibited increased fasting blood glucose, urinary glucose, and elevated renal expression of collagen 1a1 (Col1a1), fibronectin (Fn1), and smooth muscle α-actin (Acta2). Compared with Ctrl mice, Hfru-fed mice showed significantly higher serum creatinine, increased urinary protein, and reduced creatinine clearance. Adenine induced kidney injury in all +ade groups, with the most severe damage observed in Hfru−f+ade mice, as indicated by elevated blood urine nitrogen (BUN), urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), and renal fibrosis. In contrast, Hfru+f10+ade mice showed the lowest levels of these renal injury markers. The Hfru+ade diets increased renal Hif1α and iNos gene expression, which was further exacerbated by folate deficiency. Secretion of the anti-inflammatory cytokine interleukin (IL-10) by splenocytes was significantly reduced under folate-deficient conditions. Renal IL-10 levels were suppressed in all +ade groups but were significantly increased by folate supplementation. Renal IL-10 levels were negatively correlated with the inflammatory chemokine monocyte chemoattractant protein (MCP-1) and transforming growth factor (TGF)-β, whereas renal MCP-1 levels showed positive correlations with TGF-β and IL-6. Overall, these findings suggest that high fructose consumption in the absence of adequate folate intake may be of concern for CKD progression. Full article