Search Results (220)

Callistemon citrinus has shown antioxidant and anti-inflammatory properties in certain tissues. However, its impact on the brain remains unproven. This study investigates the effect of C. citrinus extract and phytosomes on the oxidative status of the brains of rats fed a high-fat–fructose diet (HFD). Fifty-four male Wistar rats were randomly divided into nine groups (n = 6). Groups 1, 2, and 3 received a standard chow diet; Group 2 also received the vehicle, and Group 3 was supplemented with C. citrinus extract (200 mg/kg). Groups 4, 5, 6, 7, 8, and 9 received a high-fat diet (HFD). Additionally, groups 5, 6, 7, 8, and 9 were supplemented with orlistat at 5 mg/kg, C. citrinus extract at 200 mg/kg, and phytosomes loaded with C. citrinus at doses of 50, 100, and 200 mg/kg, respectively. Administration was oral for 16 weeks. Antioxidant enzymes, biomarkers of oxidative stress, and fatty acid content in the brain were determined. A parallel artificial membrane permeability assay (PAMPA) was employed to identify compounds that can cross the intestinal and blood–brain barriers. The HFD group (group 4) increased body weight and adipose tissue, unlike the other groups. The brain fatty acid profile showed slight variations in all of the groups. On the other hand, group 4 showed a decrease in the activities of antioxidant enzymes SOD, CAT, and PON. It reduced GSH level, while increasing GPx activity as well as MDA, 4-HNE, and AOPP levels. C. citrinus extract and phytosomes restore the antioxidant enzyme activities and mitigate oxidative stress in the brain. C. citrinus modulates oxidative stress in brain tissue through 1.8-cineole and α-terpineol, which possess antioxidant and anti-inflammatory properties. Full article

Understanding the components of the diet, food groups, and nutritional strategies that help prevent MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) is essential for identifying dietary behaviors that can stop the progression of this condition, which currently affects over one-quarter of the global population. This review highlights the importance of including antioxidant nutrients in the diet, such as vitamins C and E, CoQ10, and polyphenolic compounds. It also emphasizes substances that support lipid metabolism, including choline, alpha-lipoic acid, and berberine. Among food groups, it is crucial to choose those that help prevent metabolic disturbances. Among carbohydrate-rich foods, vegetables, fruits, and high-fiber products are recommended. For protein sources, eggs, fish, and white meat are preferred. Among fat sources, plant oils and fatty fish are advised due to their content of omega-3 and omega-6 fatty acids. Various dietary strategies aimed at preventing MASLD should include elements of the Mediterranean diet or be personalized to provide anti-inflammatory compounds and substances that inhibit fat accumulation in liver cells. Other recommended dietary models include the DASH diet, the flexitarian diet, intermittent fasting, and diets that limit fructose and simple sugars. Additionally, supplementing the diet with spirulina or chlorella, berberine, probiotics, or omega-3 fatty acids, as well as drinking several cups of coffee per day, may be beneficial. Full article

Retinal degeneration is associated with dietary factors and environmental light exposure. This study investigated the effects of a high-fructose high-fat (HFHF) diet on susceptibility to blue light (BL)-induced retinal damage. Male ICR mice were randomized into three groups: control, BL alone, and BL plus HFHF diet (BL + HFHF). The BL + HFHF group consumed the HFHF diet for 40 weeks, followed by 8 weeks of low-intensity BL exposure (465 nm, 37.7 lux, 0.8 μW/cm²) for 6 h daily. The BL group underwent the same BL exposure while kept on a standard diet. Histopathological analysis showed that, under BL exposure, the HFHF diet significantly reduced the number of photoreceptor nuclei and the thickness of the outer nuclear layer and inner/outer segments compared to the BL group (p < 0.05). While BL exposure alone caused oxidative DNA damage, rhodopsin loss, and Müller cell activation, the combination with an HFHF diet significantly amplified the oxidative DNA damage and Müller cell activation. Moreover, the HFHF diet increased blood–retinal barrier permeability and triggered apoptosis under BL exposure. Mechanistically, the BL + HFHF group exhibited increased retinal advanced glycated end product (AGE) deposition, accompanied by the activation of the receptor for AGE (RAGE), NFκB, and the NLRP3 inflammasome-dependent IL-1β pathway. In conclusion, this study underscores that unhealthy dietary factors, particularly those high in fructose and fat, may intensify the hazard of BL and adversely impact visual health. Full article

Background/Objective: Metabolic dysfunction-associated fatty liver disease (MAFLD) is defined by the presence of hepatic steatosis, and is associated with obesity, diabetes, and other metabolic alterations. Feeding rats with a high-fat high-fructose (HFHF) diet is a reproducible experimental model of obesity/metabolic syndrome and the related MAFLD. Aronia melanocarpa, Rosa canina, and Alchemilla vulgaris are polyphenol-rich plants with proven health benefits. The aim of this study was to reveal the effects of four Aronia melanocarpa-based fruit juices (AMBFJs) in HFHF-fed rats. Methods: The AMBFJs were AM20 and AM60 (produced from aronia berries at 20 °C and 60 °C, respectively), AMRC (aronia juice with Rosa canina), and AMAV (aronia juice with Alchemilla vulgaris). Male Wistar rats were allocated to 6 groups. Except for the Control, the rest of the groups were fed an HFHF diet for 60 days. Throughout the experiment, each of the AMBFJs was administered to one HFHF-fed group. Results: HFHF-fed rats had an increased calorie intake on the background of increased liquid and decreased food consumption. At the end of the experiment, they had similar body weights, slightly increased fat indices, increased levels of blood lipids and liver enzymes, as well as typical histopathological changes in liver and adipose tissue. AMBFJs-treated animals showed improvement in most of these parameters, especially in triglyceride levels, liver enzymes, and the histopathological changes in the liver and fat. AMAV, the juice with the highest polyphenolic content, had the highest effect on adiposity. Conclusion: In HFHF-fed rats, AMBFJs exerted beneficial effects on MAFLD probably due to their polyphenolic ingredients. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are growing global health concerns. However, pharmacological therapies for MASLD/MASH have not yet been established. Dietary interventions and their bioactive components have been explored as strategies to mitigate MASLD and MASH progression. Although specific nutrients and bioactive compounds have exhibited potential therapeutic benefits, they also exacerbate adverse outcomes. In this comprehensive review, we synthesize the protective and exacerbating or sometimes dual effects of key macronutrients, including fatty acids (saturated, unsaturated, and trans fats) and carbohydrates (fructose, glucose, and sucrose), and bioactive compounds and micronutrients, in the context of MASLD management. The evidence suggests that coffee-derived compounds, such as caffeine and chlorogenic acid, may attenuate liver injury. However, the effects on MASLD severity are inconsistent. Diets high in saturated fatty acids exacerbate MASLD pathogenesis, whereas moderate intake (7–10% of total energy) may confer metabolic benefits. Other bioactive compounds and micronutrients have been explored for their diverse roles in hepatic lipid metabolism and insulin sensitivity. Although current evidence supports the therapeutic potential of specific dietary nutrients and bioactive compounds in the management of MASLD, inconsistencies in results highlight the need for more robust, well-controlled studies, including clinical trials, to clarify the preventive and therapeutic standards for balanced food interventions in MASLD management. In particular, well-designed clinical trials are necessary before clinical application. Although this is a narrative review and the literature retrieval may be biased, we covered a wide variety of substances. Full article

Background/Objectives: Neurodegenerative disorders have a complex multifactorial pathogenesis that develop decades before the initial symptoms occur. One of the crucial factors in the development of neurodegenerative disorders is an unbalanced diet. A pediatric animal model of diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) was established by feeding juvenile Iberian pigs a diet high in fat and fructose for 10 weeks. The aim of this study was to investigate the initial molecular imbalances in the frontal cortex (FC) of diet-induced juvenile MASLD pig model and determine whether these changes are associated with neuronal loss. Methods: Eighteen 15-day-old Iberian pigs were randomly assigned to either a standard diet (SD) or a Western diet (WD) for 10 weeks. A short-term recognition memory test and animal activity was recorded during the study. Animals were euthanized in week 10, and the FC and hippocampus (HIP) tissue samples were collected for immunohistochemistry and transcriptomics analyses. Results: WD-fed pigs developed MASLD. There were no significant differences in animals’ activity or recognition memory between WD and SD. To identify and quantify mature neurons, NeuN immunostaining intensity was measured, which was significantly lower in the FC of WD than SD (p ≤ 0.05), but it did not change in HIP (p ≥ 0.05). The Wnt/β-catenin pathway, which promotes neuronal survival and neurogenesis, was downregulated in FC of WD-fed pigs (p ≤ 0.05). Similarly, cytoskeleton organization and extracellular matrix biological processes were downregulated in FC of WD-fed pigs (p ≤ 0.05), whereas the mitochondrial respiratory chain complex and mitochondrion increased in FC of WD compared with SD (p ≤ 0.01). There were several other significantly modulated pathways including signal transduction, cell migration, axon guidance, and calcium ion binding. Conclusions: The high-fructose, high-fat diet led to neuronal loss in the frontal cortex of MASLD pigs and dysregulated gene expression of the Wnt/β-catenin signaling pathway, cytoskeleton organization, extracellular matrix, and mitochondrial respiratory chain—all pathways that are found deregulated in neurodegnerative diseases. Full article

Background/Objectives: The consumption of fructose-sweetened beverages, especially when combined with a high-fat (HF) diet, substantially contributes to obesity, diabetes, and metabolic dysfunction-associated steatotic liver disease. Ectopic fat accumulation in skeletal muscles is a critical factor in the development of insulin resistance, a key feature of these metabolic disorders. We aimed to investigate the effects of the rare sugar, d-allulose, on fructose-induced insulin resistance. Methods: Male Wistar rats were randomly assigned to fructose-free control diet (CD), HF/fructose-free diet (HF), or HF/fructose diet (HFF) groups. After 4 weeks, an intraperitoneal glucose tolerance test (IPGTT) was performed, followed by a two-step hyperinsulinemic–euglycemic clamp (HE-clamp) test at 5 weeks. Blood, skeletal muscle, and liver samples were collected after 6 weeks, and triglyceride (TG) levels were measured. Additionally, Western blot was performed on skeletal muscle samples. The same protocol was repeated for the HFF group supplemented with either 5% d-allulose or 5% cellulose. Results: Compared to the CD and HF groups, the HFF group exhibited increased blood glucose levels during the IPGTT and greater systemic and skeletal muscle insulin resistance in the HE-clamp. Furthermore, plasma, liver, and muscle TG levels were significantly elevated in the HFF group. However, d-allulose supplementation improved insulin resistance in the HFF group and reduced blood, liver, and muscle TG levels. Additionally, insulin-stimulated AKT phosphorylation and acetyl-CoA carboxylase phosphorylation were enhanced in the skeletal muscle following d-allulose administration. Conclusions: d-allulose may improve insulin resistance by reducing TG accumulation in the skeletal muscle, potentially independent of its anti-obesity properties. Full article

Fats play a key role in the rheological and textural properties of meat products. However, growing awareness of the link between diet and disease has stimulated research on fat replacers that can replicate these functional properties. Inulin, a β-D-fructose polymer available in various degrees of polymerization (DP), is promising as a fat replacer due to its gel-forming ability in aqueous systems and its neutral sensory profile. This study focused on optimizing the formulation of inulin gel-based fat replacers for producing reduced-fat beef burgers. A D-optimal mixture-process design was employed, considering inulin with high-DP (HDP) and low-DP (LDP). The aim was to determine the optimal amount of inulin, water, and guar gum to achieve gels with rheological properties (η, shear viscosity; K, consistency index) similar to beef fat. The optimal formulations consisted of 51.52% inulin, 48.48% water, 1.50% guar gum for LDP gel, and 39.12% inulin, 60.88% water, 1.50% guar gum for HDP gel. These gels demonstrated shear viscosity and consistency indices comparable to beef fat. While rheological behavior at constant temperatures was similar, inulin gels showed increasing viscoelastic moduli (G′ and G″) with temperature, in contrast to the melting behavior of animal fat. When used in beef burger formulations, the optimized gels resulted in improved cooking yields, reduced shrinkage, and better dimensional stability compared to conventional controls. These benefits are attributed to the hydrophilic and stabilizing properties of inulin. The findings support the use of inulin-based gels as effective fat replacers, offering a promising strategy to reduce fat content in meat products without compromising functional quality. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant global public health issue. Luteolin possesses several beneficial biological properties, including antioxidation and anti-inflammation. This study investigated luteolin’s effect and potential mechanisms on MAFLD in high-fat diet (HFD)-fed rats. Rats were administered an HFD supplemented with fructose for 12 weeks to induce MAFLD. After that, the HFD-fed rats were given either luteolin (50 or 100 mg/kg/day) or metformin (100 mg/kg/day) for 4 weeks. Luteolin improved metabolic parameters induced by the HFD, since it decreased body weight, blood pressure, fasting blood glucose, serum insulin, free fatty acids, cholesterol, and triglyceride levels (p < 0.05). Luteolin reduced hepatic injury and inflammatory markers in HFD-fed rats (p < 0.05). Additionally, HFD-fed rats treated with luteolin showed reduced malondialdehyde and raised catalase activity in plasma (p < 0.05). Luteolin attenuated hepatic steatosis compared to the untreated rats (p < 0.05). Luteolin also increased plasma adiponectin levels accompanied by upregulation of adiponectin receptor 1 (AdipoR1), AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor γ (PPAR-γ) protein expression in liver (p < 0.05). These findings revealed that luteolin ameliorated HFD-induced MAFLD in rats, possibly by reducing metabolic alterations and oxidative stress and restoring AdipoR1, AMPK, and PPARγ protein expression in HFD-fed rats. Full article

Excessive high-fat diet (HFD) intake can precipitate metabolic dysfunction-associated fatty liver disease (MAFLD). Tangeretin is a citrus flavonoid possessing many biological properties. We examined the impact of tangeretin on MAFLD and its underlying mechanism. Rats were given HFD plus 15% fructose solution for four months to produce metabolic syndrome. Metabolic syndrome rats were administered 100 mg/kg of metformin or 25 mg/kg of tangeretin for the last four weeks. HFD-induced increased body weight, liver weight, adipose tissue weight, fasting blood glucose, serum insulin, total triglyceride, total cholesterol, and free fatty acids and reduced adiponectin and high-density lipoprotein cholesterol levels in metabolic syndrome, which were alleviated by tangeretin (p < 0.05). Tangeretin stabilized alanine transaminase activity, liver catalase, and inflammatory and oxidative stress markers in HFD rats compared to untreated HFD rats (p < 0.05). Tangeretin reduced hepatic steatosis induced by HFD. Downregulation of hepatic insulin receptor substrate-1 (IRS-1) and protein kinase B (Akt) protein expression in metabolic syndrome rats was recovered by tangeretin (p < 0.05). Metformin, an antihyperglycemic drug, produced comparable effects to tangeretin. In conclusion, tangeretin attenuates metabolic disorders and fatty liver induced by HFD in rats. The underlying mechanisms involve reducing oxidative stress, and inflammation and enhancing insulin sensitivity. Full article

Obesity remains a major epidemic in developed countries, with a limited range of effective pharmacological treatments. The pharmacological modulation of PPARα, CB1, or GLP-1 receptor activity has demonstrated beneficial effects, including anti-obesity actions. In this study, we evaluated a novel amide derivative of oleic acid and tyrosol (Oleyl hydroxytyrosol ether, OLHHA), a PPARα agonist, and CB1 antagonist, in combination with the GLP-1 agonist liraglutide (LIG), as an effective multitarget therapy to improve both the peripheral and central alterations in an animal model of diet-induced obesity. In rats, exposure to a high-fat high-fructose diet (HFHFD) induced weight gain and increased plasma triglycerides, LDL, and hepatic parameters. In the brain, the HFHFD provoked disruptions in the expression of proteins regulating food intake, the endocannabinoid system, the insulin pathway, and inflammation and resulted in altered tau expression and phosphorylation, thus indicating neurodegenerative changes. Based on our results, the administration of LIG or OLHHA alone was insufficient to completely reverse the alterations noticed at the peripheral and central levels. On the other hand, the combined treatment with both compounds (OLHHA+LIG) was the most effective in promoting body weight loss and ameliorating both the central and peripheral alterations induced by HFHFDs in rats. This multitarget therapeutic approach could represent a promising strategy for treating obesity and associated comorbidities. Full article

Metabolic dysfunction and hepatic abnormalities, such as those associated with high-fat, high-fructose (HFHFr) diets, are major contributors to obesity-related health issues. The growing interest in sustainable dietary interventions has highlighted the potential of plant-based byproducts. Dragon fruit (Hylocereus undatus) peel waste, rich in bioactive compounds such as dietary fibers, phenolics, and betacyanins, represents a promising functional ingredient for managing these disorders. This study investigated the effects of dragon fruit peel powder (DFP) on metabolic dysfunction and hepatic abnormalities induced by a HFHFr diet in rats. Over 12 weeks, the rats were fed a standard AIN-93M diet (control or C), C with 5% (w/w) DFP (C + DFP), a HFHFr diet, or a HFHFr diet with 5% (w/w) DFP (HFHFr + DFP). DFP supplementation significantly reduced HFHFr-induced body weight gain, visceral adiposity, insulin resistance, and dyslipidemia while also lowering systolic blood pressure and systemic oxidative stress markers. In the liver, DFP supplementation attenuated fat accumulation and lipid peroxidation, reduced glycogen storage abnormalities, and modulated the expression of lipid metabolism and inflammatory genes. These findings suggest that DFP may serve as a functional dietary supplement for preventing and managing metabolic disorders and liver abnormalities associated with excessive fat and fructose consumption. Full article

Metabolic syndrome (MetS) constitutes a spectrum of interconnected conditions comprising obesity, dyslipidemia, hypertension, and insulin resistance (IR). While a singular, all-encompassing treatment for MetS remains elusive, an integrative approach involving tailored lifestyle modifications and emerging functional food therapies holds promise in preventing its multifaceted manifestations. Our main objective was to scrutinize the efficacy of cranberry proanthocyanidins (PAC, 200 mg/kg/day for 12 weeks) in mitigating MetS pathophysiology in male mice subjected to standard Chow or high-fat/high-fructose (HFHF) diets while unravelling intricate mechanisms. The administration of PAC, in conjunction with an HFHF diet, significantly averted obesity, evidenced by reductions in body weight, adiposity across various fat depots, and adipocyte hypertrophy. Similarly, PAC prevented HFHF-induced hyperglycemia and hyperinsulinemia while also lessening IR. Furthermore, PAC proved effective in alleviating key risk factors associated with cardiovascular diseases by diminishing plasma saturated fatty acids, as well as levels of triglycerides, cholesterol, and non-HDL-C levels. The rise in adiponectin and drop in circulating levels of inflammatory markers showcased PAC’s protective role against inflammation. To better clarify the mechanisms behind PAC actions, gut–liver axis parameters were examined, showing significant enhancements in gut microbiota composition, microbiota-derived metabolites, and marked reductions in intestinal and hepatic inflammation, liver steatosis, and key biomarkers associated with endoplasmic reticulum (ER) stress and lipid metabolism. This study enhances our understanding of the complex mechanisms underlying the development of MetS and provides valuable insights into how PAC may alleviate cardiometabolic dysfunction in HFHF mice. Full article

The intake of oleic acid-rich fats, a hallmark of the Mediterranean diet, has well-documented beneficial effects on human metabolic health. One of the key mechanisms underlying these effects is the regulation of gut microbiota structure and function. However, most existing studies focus on gut bacteria, while gut fungi, as a vital component of the gut microbiota, remain largely unexplored. This study compared the effects of regular peanut oil (PO) and high-oleic acid peanut oil (HOPO) on the gut mycobiome and serum metabolome employing ITS high-throughput sequencing and UPLC-MS/MS metabolomics to explore how dietary fatty acid composition influences gut microecology. Both HOPO and PO effectively reversed high-fat, high-fructose diet (HFFD)-induced reductions in gut fungal diversity, with HOPO showing superior efficacy in restoring gut microbiome balance, as reflected by an improved fungal-to-bacterial diversity ratio and reduced abundance of pathogenic fungi such as Aspergillus, Penicillium, and Candida. Furthermore, HOPO demonstrated a greater ability to normalize serum bile acid levels, including taurochenodesoxycholic acid, and to reverse elevated pantothenol levels, suggesting its potential role in maintaining bile acid metabolism and CoA biosynthesis. In summary, HOPO is more effective than PO in maintaining the normal structure and function of gut mycobiome in HFFD-fed SD rats. Full article

Insulin resistance (IR) is one of the important causes of metabolic dysfunction-associated steatotic liver disease (MASLD). Apolipoprotein A-I (apoA-I) is secreted primarily by hepatocytes and plays an essential role in reverse cholesterol transport. Our previous studies revealed that apoA-I can mitigate the progression of metabolic dysfunction-associated steatohepatitis (MASH). However, there is no clear evidence to explain the relationship between apoA-I and IR. Here, we investigated the effects of apoA-I overexpression on IR in both HepG2 cells and mice. In vitro experiment results revealed that apoA-I overexpression can promote cellular glucose uptake in oleic acid-induced IR in HepG2 cells. High-fat, high-cholesterol, and high-fructose diets were used to induce IR in mice. The results showed that apoA-I overexpression improved glucose tolerance, reduced serum insulin levels, and ameliorated IR in diet-induced MASLD mice. Moreover, apoA-I promoted the expression of peroxisome proliferator-activated receptor α (PPARα) in the nucleus both in vitro and in vivo. In conclusion, apoA-I could alleviate MASLD by reducing IR in mice and might exert this effect through the PPARα pathway. Full article