Search Results (1,421)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major contributor to liver-related morbidity, cardiovascular disease, and metabolic complications. Lifestyle interventions, including diet and exercise, are first line in treating MASLD. Dietary approaches such as the low-glycemic-index Mediterranean diet, the ketogenic diet, intermittent fasting, and high fiber diets have demonstrated potential in addressing the metabolic dysfunction underlying this condition. The development and progression of MASLD are closely associated with taxonomic shifts in gut microbial communities, a relationship well-documented in the literature. Given the importance of diet as a primary treatment for MASLD, it is important to understand how gut microbiota and their metabolic byproducts mediate favorable outcomes induced by healthy dietary patterns. Conversely, microbiota changes conferred by unhealthy dietary patterns such as the Western diet may induce dysbiosis and influence steatotic liver disease through promoting hepatic inflammation, up-regulating lipogenesis, dysregulating bile acid metabolism, increasing insulin resistance, and causing oxidative damage in hepatocytes. Although emerging evidence has identified links between diet, microbiota, and development of MASLD, significant gaps remain in understanding specific microbial roles, metabolite pathways, host interactions, and causal relationships. Therefore, this review aims to provide mechanistic insights into the role of microbiota-mediated processes through the analysis of both healthy and unhealthy dietary patterns and their contribution to MASLD pathophysiology. By better elucidating the interplay between dietary nutrients, microbiota-mediated processes, and the onset and progression of steatotic liver disease, this work aims to identify new opportunities for targeted dietary interventions to treat MASLD efficiently. Full article

Introduction: Copper is an essential trace element crucial for enzyme synthesis and metabolism. Adequate copper levels are beneficial for maintaining the normal immune function of the spleen. Copper deficiency disrupts the metabolic processes within the spleen and impairs its immune function. This research examines the impact of copper deficiency on the spleen and the potential recovery following copper supplementation. Methods: Weaned mice underwent a 4-week copper-deficient diet, succeeded by 1-week of copper repletion via intraperitoneal copper sulfate injection. Histological examination was used to assess pathological changes in the spleen. Biochemical assays were performed to measure oxidative stress levels in the spleen. ELISA, qPCR, and Western blot were employed to examine alterations in inflammatory markers, immune indicators, and oxidative regulatory factors across various levels. Results: Copper deficiency caused histological damage to the spleen, altered the expression of oxidative stress regulatory pathways (Nrf2, Keap1, and HO-1), and affected the expression of key inflammatory enzymes (iNOS, COX2) and transcription factor NF-κB, leading to oxidative damage. This was reflected by decreased levels of SOD, GSH, and T-AOC, along with increased levels of CAT and MDA. The levels of inflammatory cytokines IL-1β, TNF-α, IL-6, and IL-8 were notably increased. Copper supplementation significantly improved these changes. Conclusions: Copper deficiency leads to spleen tissue damage in mice, affecting the Nrf2 regulatory pathway and inducing oxidative damage. Subsequent copper supplementation with copper sulfate effectively ameliorates the damage caused by copper deficiency. Full article

Background: Atherosclerotic calcification (AC) is a common feature of atherosclerotic cardiovascular disease. β-Hydroxybutyrate (BHB) has been identified as a molecule that influences cardiovascular disease. However, whether BHB can influence AC is still unknown. Methods and Results: In this study, ApoE^−/− mice, fed a Western diet, were used to examine the effects of BHB on AC. Rat vascular smooth muscle cells (VSMCs) were used to verify the impacts of BHB on AC and to explore the underlying mechanisms. The results show that Western diet-challenged ApoE^−/− mice, supplemented with BHB for 24 weeks, exhibited reduced calcified areas, calcium content, and alkaline phosphatase (ALP) activity in the aortas, as well as ameliorated severity of AC. Furthermore, BHB downregulated the expression of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), thereby reducing endoplasmic reticulum stress (ERS) and ERS-mediated apoptosis in the aortas of the mice. Consistently, in vitro studies showed that BHB reduced ALP activity and calcium content in VSMCs, and inhibited VSMC calcification. Additionally, BHB suppressed ERS-mediated apoptosis in VSMCs. Conclusions: In summary, the present results demonstrate that BHB can alleviate atherosclerotic calcification by inhibiting ERS-mediated apoptosis. Therefore, BHB may serve as a viable therapeutic agent for AC. Full article

Background/Objectives: UFMylation, a newly identified ubiquitin-like modification, modulates a variety of physiological processes, including endoplasmic reticulum homeostasis maintenance, DNA damage response, embryonic development, and tumor progression. Recent reports showed that UFMylation plays a protective role in preventing liver steatosis and fibrosis, serving as a defender of liver homeostasis in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the regulation of UFMylation in MASLD remains unclear. This study aimed to determine the expressed patterns of UFMylation components in multiple tissues of leptin-deficient ob/ob mice and high-fat diet (HFD)-fed mice, which are mimicking the conditions of MASLD. Methods: The ob/ob mice and HFD-fed mice were sacrificed to collect tissues indicated in this study. Total RNA and proteins were extracted from tissues to examine the expressed patterns of UFMylation components, including UBA5, UFC1, UFL1, DDRGK1, UFSP1, UFSP2 and UFM1, by real-time PCR and western blot analysis. Results: The protein levels of UBA5, UFC1 and UFL1 were down-regulated in liver, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT), whereas the messenger RNA (mRNA) levels of Ufl1 and Ufsp1 were both decreased in skeletal muscle, BAT, iWAT and epididymal white adipose tissue (eWAT) of ob/ob mice. In contrast, the mRNA levels of Ufsp1 in skeletal muscle, BAT, iWAT and heart, and the protein levels of UFL1 were decreased in BAT, iWAT, heart and cerebellum of HFD-fed mice. Conclusions: Our findings established the expressed profiles of UFMylaiton in multiple tissues of mice mimicking MASLD, indicating an important regulation for UFMylation in these tissues’ homeostasis maintenance. Full article

Polyunsaturated fatty acids (PUFAs) are vital dietary elements that play a significant role in human nutrition. They are highly regarded for their positive contributions to overall health and well-being. Beyond the fact that they provide a substantial supply of energy to the body (a role that saturated fats can also perform), these unsaturated fatty acids and, especially, the essential ones are involved in cell membrane structure, blood pressure regulation, and coagulation; participate in the proper functioning of the immune system and assimilation of fat-soluble vitamins; influence the synthesis of pro- and anti-inflammatory substances; and protect the cardiovascular system. Modern diets like the Western diet and the American diet are rich in saturated fats found especially in fast food products, sweets, and processed foods, a fact that has led to an increase in the prevalence of metabolic diseases worldwide (obesity, type II diabetes, gout, cardiovascular disease). Nutritionists have drawn attention to the moderate consumption of saturated fats and the need to increase the intake of unsaturated fats to the detriment of saturated ones. This paper examines the biochemical roles of polyunsaturated fats, particularly essential fatty acids, and contrasts their benefits with the detrimental effects of saturated fat overconsumption. Furthermore, it highlights the necessity for dietary shifts towards increased PUFA intake to mitigate the global burden of diet-related health issues. The co-occurrence of PUFAs and polyphenols in plant-based foods highlights the sophistication of nature’s design. These bioactive compounds are not randomly distributed but are present in foods humans have consumed together historically. From traditional diets like the Mediterranean, which pairs olive oil (PUFAs and polyphenols) with vegetables and legumes, to Asian cuisines combining sesame seeds with turmeric, cultural practices have long harnessed this natural synergy. Full article

The gut microbiota plays a key role in health and disease, but it could be affected by various factors (diet, lifestyle, environment, genetics, etc.). Focusing on diet, while the role of the different styles and choices (Mediterranean vs. Western diet, vegan or vegetarian diets) has been extensively studied, there are a few comprehensive papers on the effects of additives and food processing. Therefore, the main goal of this manuscript is to propose an overview of the link between ultra-processed foods and the gut microbiota based on papers and data available in the literature. The literature search was performed on PubMed and Clinicaltrials.gov, and after the selection of the most relevant articles, the paper proposes a synopsis of the effects of some classes of additives (sweeteners, preservatives, emulsifiers, glutamate, etc.), as well as of some treatments, on the gut microbiota and some pathological conditions. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by the accumulation of fat in the liver, excluding excessive alcohol consumption and other known causes of liver injury. Animal models are often used to explore different pathogenic mechanisms and therapeutic targets of MASLD. The aim of this study is to apply an artificial intelligence (AI) system based on second-harmonic generation (SHG)/two-photon-excited fluorescence (TPEF) technology to automatically assess the dynamic patterns of hepatic steatosis in MASLD mouse models. Methods: We evaluated the characteristics of hepatic steatosis in mouse models of MASLD using AI analysis based on SHG/TPEF images. Six different models of MASLD were induced in C57BL/6 mice by feeding with a western or high-fat diet, with or without fructose in their drinking water, and/or by weekly injections of carbon tetrachloride. Results: Body weight, serum lipids, and liver enzyme markers increased at 8 and 16 weeks in each model compared to baseline. Steatosis grade showed a steady upward trend. However, the non-alcoholic steatohepatitis (NASH) Clinical Research Network (CRN) histological scoring method detected no significant difference between 8 and 16 weeks. In contrast, AI analysis was able to quantify dynamic changes in the area, number, and size of hepatic steatosis automatically and objectively, making it more suitable for preclinical MASLD animal experiments. Conclusions: AI recognition technology may be a new tool for the accurate diagnosis of steatosis in MASLD, providing a more precise and objective method for evaluating steatosis in preclinical murine MASLD models under various experimental and treatment conditions. Full article

Background: Proactively preventing postpartum weight retention (PPWR) is one of the effective intervention strategies to reduce the occurrence of obesity in women. Population studies have shown that serum folate levels are closely related to body weight. The regulation of folic acid on lipid metabolism has been fully confirmed in both in vivo and in vitro studies. For many years, folic acid supplementation has been widely used in periconceptional women due to its role in preventing fetal neural tube defects. However, whether folic acid supplementation prior to and throughout pregnancy exerts preventive effects on PPWR remains uncertain. This study aims to investigate the preventive effect of folic acid on PPWR in rats and further explore the underlying mechanisms. Methods: In this study, pregnant rats were administered one of the dietary schedules: control diet (CON), high-fat diet (HF), control diet combined with folic acid (FA) and high-fat diet combined with folic acid (HF + FA). Results: We discovered that folic acid supplementation inhibited high-fat diet-induced elevations in body weight, visceral fat weight, liver weight, hepatic lipid levels and serum lipid levels at 1 week post-weaning (PW). Western blot analysis showed that folic acid supplementation inhibited the expression of endoplasmic reticulum (ER) stress-specific proteins including GRP78, PERK, eIF2α, IRE1α, XBP1 and ATF6, subsequently decreasing the expression of proteins related to lipid synthesis including SREBP-1c, ACC1 and FAS. Conclusions: In conclusion, folic acid supplementation prior to and throughout pregnancy exerts preventive effects on high-fat diet-induced PPWR in rats, and the mechanism is associated with the inhibition of ER stress-mediated lipogenesis signaling pathways in the liver. Folic acid supplementation may serve as a potential strategy for preventing PPWR. In the future, the effectiveness of folic acid in PPWR prevention can be further verified by population studies. Full article

This study demonstrates the effectiveness of propidium iodide as a reliable marker for detecting dead or dying cells in frozen liver tissue sections. By comparing propidium iodide staining with the widely used Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, both methods showed consistent results in disease models such as alcohol-induced fibrosis and Western diet-induced fatty liver. Additionally, propidium iodide was successfully co-stained with other fluorescent markers, like phalloidin (for actin filaments) and antibodies targeting collagen, enabling detailed spatial analysis of dying cells within tissue. This multiplex approach allows for a deeper understanding of tissue organization and cell death localization, particularly in complex conditions like liver fibrosis. Moreover, our results suggest that propidium iodide staining can be applied beyond current models, offering a more accessible and cost-effective alternative to traditional methods, like TUNEL. Furthermore, its integration with other markers enables simultaneous analysis of immune responses and tissue damage, making it a powerful tool for future studies on liver disease and other inflammatory conditions. This technique has the potential to advance research into disease mechanisms and improve the evaluation of novel therapeutic strategies targeting tissue regeneration and inflammation control. Full article

Background: Chronic low-grade inflammation in obesity is linked to white adipose tissue (WAT) dysfunction. Plasma lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4), triggering NF-κB and worsening these disturbances. Previously, we showed that histone H3 lysine 27 (H3K27) epigenetic modifications affect WAT gene expression in high-fat-diet mice, identifying key pathways in adipose-derived stem cells (ASCs). This study explores whether NF-κB influences H3K27 modifiers in human ASCs and evaluates fish oil (FO) as a modulator. Methods: Human visceral WAT ASCs were stimulated with LPS and treated with FO enriched with eicosapentaenoic acid (EPA). Flow cytometry, PCR array, RT-PCR, and Western blot assays were used. Results: LPS increased NF-κB activity, elevating KDM6B demethylase levels and H3K27 acetylation. These epigenetic modifications in LPS-stimulated ASCs were associated with persistent changes in the expression of genes involved in adipogenesis, metabolic regulation, and inflammation, even after LPS removal and cell differentiation. FO mitigated these effects, reducing H3K27 acetylation and promoting methylation. Conclusions: FO demonstrates potential in modulating inflammation-induced epigenetic changes and preserving adipocyte function. Full article

Background: Soybeans are a widely consumed legume, essential in Western diets and especially prominent in vegan and vegetarian nutrition. However, environmental contamination from anthropogenic sources, such as industrial emissions, wastewater, and pesticide use, has led to the accumulation of non-essential and toxic elements in legumes, potentially impacting human health. Method: This study quantified the levels of 11 potential toxic elements (Al, B, Ba, Cd, Co, Cr, Li, Ni, Pb, Sr, V) in 90 samples of four soybean species (Glycine max, Vigna radiata, Vigna angularis, Vigna mungo) using inductively coupled plasma optical emission spectrometry (ICP-OES). Results: Results showed that boron had the highest mean content (9.52 mg/kg ww), followed by aluminum (6.73 mg/kg ww). Among the toxic metals, cadmium was most concentrated in green soybeans (0.03 mg/kg ww), and black soybeans had the highest level of lead (0.07 mg/kg ww). Based on an average soybean consumption of 50 g/day, no immediate health risk was detected. However, lithium and nickel were present in substantial amounts, with lithium contributing 31.43–48.57% and nickel 6.81–39.56% of their respective provisional daily intake limits, especially from red soybeans (V. angularis). Conclusions: This study highlights the importance of monitoring toxic elements in soybeans and calls for stricter environmental management practices to minimize contamination, ensuring the safety of soy products as their global consumption rises. Full article

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder with no established pharmacotherapy. Quercetin, a polyphenolic flavonoid, demonstrates potential hepatoprotective effects but has limited bioavailability. This study evaluates the impact of quercetin on NAFLD and assesses the roles of autophagy-related proteins in disease progression. Methods: Forty-seven male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce NAFLD, followed by quercetin treatment for 4 weeks. Mice were divided into baseline, control, and two quercetin groups, receiving low (10 mg/kg) and high (50 mg/kg) doses. Liver histology was scored using the NAFLD Activity Score (NAS). Immunohistochemistry and immunoblotting were performed to analyze autophagy markers. Results: Quercetin-treated groups showed significant reductions in NAS compared to controls (p = 0.011), mainly in steatosis and steatohepatitis. Immunohistochemistry indicated increased expression of autophagy markers LCA and p62 in quercetin groups. Western blot analysis revealed significant elevations in LC3A in the treated groups, suggesting improved autophagic activity and lipid degradation. Conclusions: Quercetin effectively reduces NAFLD severity and modulates autophagy-related proteins. These findings suggest that quercetin enhances autophagic flux, supporting its therapeutic potential for NAFLD. Additional research is needed to clarify the molecular mechanisms of quercetin and to determine the optimal dosing for clinical application. Full article

The literature on the postprandial metabolic changes in individuals with Metabolic Syndrome (MetS) remains limited, despite the fact that postprandial states represent the most common physiological condition in Western societies. Background/Objectives: The objective of this study was to investigate the plasma metabolomics profile in both fasting and postprandial states following a high-fat challenge in individuals with MetS who consumed diets with varying quantities and qualities of dietary fat over 12 weeks. Methods: Seventy-five patients with MetS (28 males and 47 females) from the Spanish LIPGENE cohort were included in the study. MetS patients were randomly stratified to follow one of four dietary interventions (isoenergetic diets) for a 12-week long-term study. The four diets were high in saturated fatty acids and high in monounsaturated fatty acids (HSFA and HMUFA), low-fat high-complex carbohydrates (LFHCC), and LFHCC supplemented with n-3. The metabolomics analysis of plasma samples was carried out using Liquid Chromatography Time-of-Flight Mass Spectrometry (LC-TOF/MS). Results: We observed a decrease in inflammation biomarkers, including acetylcarnitine and L-carnitine during the fasting state and hexanoyl-L-carnitine and isobutyryl-L-carnitine during the postprandial period, mediated by the replacement of HSFA with HMUFA. Additionally, antioxidant compounds such as 4-hydroxybenzaldehyde and L-valine were expressed at higher levels after consumption of the HMUFA diet compared to the HSFA diet. HSFA also presented altered levels of phosphatidylcholine, a metabolite previously linked with insulin resistance. Conclusions: These findings suggest that replacing HSFA with HMUFA may reduce inflammation and improve antioxidant profiles, supporting the potential for tailored dietary interventions in individuals with MetS. Full article

Consuming a “modern” Western diet and overnutrition may increase insulin secretion. Additionally, nutrition-mediated hyperinsulinemia is a major driver of ectopic fat deposition. The global prevalence of metabolic syndrome is high and growing. Within this context, people with congenital lipodystrophy often experience a severe form of metabolic syndrome. Evidence is increasingly supporting that subtle partial lipodystrophy plays an important role in the development of metabolic syndrome in the general population. In individuals in the general population with subtle partial lipodystrophy, as well as in those with congenital lipodystrophy, the subcutaneous adipose tissues are unable to accommodate surplus energy intake. In both conditions, (excess) fat is directed toward the liver, pancreas, and muscles, where it is deposited as ectopic fat, as this fat can no longer be stored in the “safe” subcutaneous fat depots. Ectopic fat depositions cause insulin resistance in the liver and muscles, as well as β-cell dysfunction in the pancreas. Support of a direct pathological role of ectopic fat deposition in this condition is further provided by the rapid normalization of hepatic insulin sensitivity and improvement in pancreatic β-cell function after marked reductions in ectopic fat depositions. Thus, ectopic fat deposition in the liver, pancreas, and muscles may play a causal role in the pathogenesis of metabolic syndrome even in the general population. As such, the prevention of ectopic fat deposition may reduce the risk of metabolic syndrome and mitigate its effects. Full article

Obesity has emerged as a major risk factor for human health, exacerbated by aging and changes in dietary habits. It represents a significant health challenge, particularly for older people. While numerous studies have examined the effects of obesity and aging on fat metabolism independently, research on their combined effects is limited. In the present study, the protective action against white fat accumulation after a high-fat diet (HFD) exerted by exogenous melatonin, a circadian hormone endowed with antioxidant properties also involved in fat metabolism, was investigated in a mouse model. For this purpose, a battery of tests was applied before and after the dietary and melatonin treatments of the animals, including epididymal white adipose tissue (eWAT) histological evaluations, transcriptomic and lipidomic analyses, real-time PCR tests, immunofluorescence staining, Western blot, the appraisal of serum melatonin levels, and transmission electron microscopy. This study found that aged mice on a high-fat diet (HFD) showed increased lipid deposition, inflammation, and reduced antioxidant glutathione (GSH) levels compared to younger mice. Lipidomic and transcriptomic analyses revealed elevated triglycerides, diglycerides, ceramides, and cholesterol, along with decreased sphingomyelin and fatty acids in eWAT. The genes linked to inflammation, NF-κB signaling, autophagy, and lipid metabolism, particularly the melatonin and glutathione pathways, were significantly altered. The aged HFD mice also exhibited reduced melatonin levels in serum and eWAT. Melatonin supplementation reduced lipid deposition, increased melatonin and GSH levels, and upregulated AANAT and MTNR1A expression in eWAT, suggesting that melatonin alleviates eWAT damage via the MTNR1A pathway. It also suppressed inflammatory markers (e.g., TNF-α, NLRP3, NF-κB, IL-1β, and CEBPB) and preserved mitochondrial function through enhanced mitophagy. This study highlights how aging and HFD affect lipid metabolism and gene expression, offering potential intervention strategies. These findings provide important insights into the mechanisms of fat deposition associated with aging and a high-fat diet, suggesting potential intervention strategies. Full article