Search Results (1,168)

Background/Objectives: The dietary inflammatory index (DII) has been widely used to examine dietary inflammation in chronic diseases; however, the relative contribution of individual nutrients to the total DII score remains unclear. Identifying nutrient clusters that strongly influence the energy-adjusted DII (E-DII) in patients with diabetes and prediabetes may provide practical guidance for dietary counselling and intervention. This study aimed to identify nutrient clusters based on dietary intake and examine their association with the E-DII in patients with diabetes and prediabetes. Methods: In total, 408 dietary records of 17 patients were analysed. The E-DII was calculated from the reported dietary intake using photographs. Exploratory factor analysis was used to derive nutrient clusters, and ordinary logistic regression analysis was applied to examine their association with the E-DII tertiles. Results: Five nutrient clusters (antioxidant-mineral, protein-B complex, fatty acids, plant-lipids, and immune-modulating micronutrients) were extracted, explaining 69.3% of the total variance. Ordinary logistic regression showed that antioxidant-mineral, fatty acids, and immune-modulating micronutrients predicted classification between low, intermediate, and high E-DII groups. Conclusions: Antioxidant-mineral, fatty acids, and immune-modulating micronutrients were associated with a lower probability of belonging to the pro-inflammatory group. The identification of these clusters highlighted specific nutrient combinations that may protect against diet-induced inflammation. These results provided clinically relevant evidence that nutritional strategies emphasising fruits, vegetables, healthy fats, and balanced protein sources may contribute to lowering dietary inflammatory potential and improving metabolic health in patients with diabetes and prediabetes. Full article

Background/Objectives: Autologous conditioned serum (ACS) is an intra-articular orthobiologic for osteoarthritis (OA) intended to shift the joint cytokine milieu toward an anti-inflammatory, pro-regenerative profile. In the present study, we compared the molecular composition of ACS (specifically IMPACT^® ACS) from OA patients with that of healthy controls and assessed demographic and lifestyle influences on mediator levels. Methods: ACS was prepared from the whole blood of 50 OA patients and 20 healthy controls using the IMPACT^® centrifugation system (Plasmaconcept, Cologne, Germany) with glass-bead incubation and standardized handling. Cytokines, growth factors, and matrix metalloproteinases (MMPs) were quantified using multiplex immunoassays and ELISA. To account for demographic imbalances across cohorts, the primary findings were verified using age- and sex-adjusted multiple linear regression models. Results: Pro-inflammatory mediators were minimal in both cohorts, with IL-1β undetectable and IL-6 and TNF-α at very low levels. IL-1 receptor antagonist (IL-1RA) was consistently present. Notably, OA-derived ACS exhibited a catabolic shift compared to controls, characterized by significantly higher MMP-2 and MMP-3 levels. Growth factor profiling showed lower TGF-β1 and TGF-β3 in OA-derived ACS, with TGF-β2 showing no significant difference after adjustment. Exploratory stratified analyses indicated potential differences across sex, BMI, smoking status, and diet for select mediators, though subgroup sizes were limited. Conclusions: ACS prepared with a standardized IMPACT^® protocol displays a broad anti-inflammatory profile. However, increased MMPs and isoform-specific differences in TGF-β reflect a disease-associated molecular imprint. Consequently, patient-related heterogeneity supports the need for standardized reporting and motivates further research into stratified ACS therapy. Full article

Obesity is associated with profound metabolic, inflammatory, and neurobehavioral dysfunctions. Dietary interventions leading to weight loss are commonly employed, yet it remains unclear whether all obesity-related alterations are fully reversed upon reaching normal body weight. Poor adherence to dietary regimens often results in weight cycling, or yo-yo dieting, characterized by repeated episodes of weight gain and loss, a phenomenon linked to adverse health outcomes. Here, we investigated the consequences of weight cycling in C57BL/6J mice. The Control Group was maintained on a standard chow diet throughout the protocol, whereas the experimental group underwent two alternating cycles of high-fat diet feeding (weight gain) and standard diet reversion (weight loss), until the end of the protocol where both groups reached 80 weeks of age. Despite achieving a final body weight and glucose and lipid metabolic profile comparable to lean controls, weight-cycled mice exhibited impaired sensorimotor function, increased anxiety-like behavior (evaluated through behavioral tests), and persistent inflammation, including a peritoneal macrophage pro-inflammatory profile and adipose tissue infiltration. We define this phenomenon as “obesogenic inflammatory memory”, highlighting that obesity leaves an immunological imprint that sustains inflammation even after normalization of weight and metabolic parameters. These findings demonstrate that weight cycling is associated with chronic macrophage-mediated inflammatory states, linked to long-term behavioral and neurological manifestations, and opening new avenues for future investigation and therapeutic approaches. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a prevalent chronic liver disease characterized by hepatocellular injury, inflammation, and lipid accumulation, for which effective pharmacotherapies remain limited. Tissue acidification has emerged as a critical inflammatory cue in metabolic diseases; however, whether proton-sensing signaling contributes to MASH pathogenesis is largely unknown. Here, we identify the proton-sensing G protein-coupled receptor GPR68 (OGR1) as a key inflammatory and metabolic regulator in diet-induced MASH. In a high-fat diet-induced mouse model, hepatic GPR68 expression was markedly upregulated during MASH progression. Inhibiting GPR68 with ogremorphin significantly ameliorated MASH pathology, as evidenced by reduced hepatic inflammation and lipid accumulation, improved histological features, and attenuated expression and release of pro-inflammatory cytokines, including IL-6 and TNF-α. Mechanistically, GPR68 inhibition dampened acidification-associated inflammatory signaling in the liver. Together, these findings establish GPR68 as a tractable proton-sensing inflammatory node that links tissue acidification to metabolic liver injury and highlight GPR68 as a promising therapeutic strategy for MASH. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and is characterized by excessive lipid accumulation in hepatocytes. Endoplasmic reticulum (ER) stress and inflammation play important roles in hepatic lipid accumulation. Although CILP2 has been implicated in lipid metabolism, its role in MASLD remains unclear. Hepatic steatosis was induced in mice by a high-fat diet in this study. CILP2 was overexpressed in mouse livers and in vitro hepatocytes using the Ad-CILP2 adenovirus. CILP2 KO mice were also used in the experiments. Liver tissues and hepatocytes were collected for further analysis. CILP2 expression was upregulated in steatotic liver tissue and hepatocytes. CILP2 overexpression upregulated genes related to fatty acid synthesis (Srebp-1c, Fasn, Acc, Scd1, and Cd36), promoted lipid accumulation, and elevated the expression of proinflammatory cytokines (Il6, Tnf, and Il1b). Conversely, CILP2 knockout reduced high-fat diet-induced hepatic steatosis and improved glucose metabolism. Mechanistically, CILP2 activated the IRE1α/XBP1 branch of the ER stress pathway, thereby promoting lipid synthesis and inflammation, effects that were partially alleviated by 4-PBA and STF-083010 treatments. Our findings indicate that CILP2 contributes to hepatic lipid accumulation and inflammation via the IRE1α/XBP1 pathway and may represent a potential therapeutic target for MASLD intervention. Full article

Metabolic associated fatty liver disease (MAFLD), redefined from non-alcoholic fatty liver disease (NAFLD), is a global health concern driving the search for dietary interventions based on natural compounds. Phloroglucinaldehyde (PGA), a primary phenolic metabolite of the widely consumed anthocyanin cyanidin-3-glucoside (C3G) found in berries and other fruits, has emerged as a promising candidate due to its potential higher bioavailability than its parent compound. This study investigates the protective effects of PGA against high-fat diet (HFD)-induced MAFLD. Using both in vitro (LO2 cells) and in vivo (C57BL/6J mice) models, we found that PGA administration significantly attenuated body weight gain and hepatic steatosis, while reducing serum levels of TG, TC, liver transaminases (AST & ALT), and insulin resistance (p < 0.05). Further liver lipidomic profiling revealed that PGA supplementation specifically down-regulated 46 lipid species (p < 0.05), predominantly triglycerides characterized by long-chain and very-long-chain saturated fatty acids. Mechanistically, PGA enhanced the hepatic antioxidant capacity by increasing superoxide dismutase (SOD) activity (p < 0.05) and decreasing malondialdehyde (MDA) (p < 0.05) and exerted anti-inflammatory effects by reducing pro-inflammatory cytokines (IL-6, TNF, MCP-1) (p < 0.05) and endotoxin levels (p < 0.05). Correlation analyses further linked the down-regulated lipids to improvements in oxidative stress and inflammation. Our findings underscore that PGA, a key bioactive metabolite derived from dietary anthocyanins, alleviates MAFLD through its potent antioxidant and anti-inflammatory properties, highlighting its potential as a functional food ingredient or nutraceutical for metabolic health. Full article

This study investigates whether fecal microbiota transplantation (FMT) can alleviate gut microbiota dysbiosis induced by a high-fat diet (HFD) through modulation of fatty acid metabolism, competition for nutrients, production of short-chain fatty acids (SCFAs), and restoration of mucus layer integrity. To elucidate the mechanisms by which FMT regulates colonic microbial function and host metabolic responses, 80 male Bal b/c mice were randomly assigned to four experimental groups (n = 20 per group): Normal Diet Group (NDG), High-Fat Diet Group (HDG), Restrictive Diet Group (RDG), and HDG recipients of NDG-derived fecal microbiota (FMT group). The intervention lasted for 12 weeks, during which body weight was monitored biweekly. At the end of the experiment, tissue and fecal samples were collected to assess digestive enzyme activities, intestinal histomorphology, gene expression related to gut barrier function, and gut microbiota composition via 16S rRNA gene sequencing. Results showed that mice in the HDG exhibited significantly higher final body weight and greater weight gain compared to those in the NDG and RDG (p < 0.05). Notably, FMT treatment markedly attenuated HFD-induced weight gain (p < 0.05), reducing it to levels comparable with the NDG (p > 0.05). While HFD significantly elevated the activities of α-amylase and trypsin (p < 0.05), FMT supplementation effectively suppressed these enzymatic activities (p < 0.05). Moreover, FMT ameliorated HFD-induced intestinal architectural damage, as evidenced by significant increases in villus height and the villus height-to-crypt depth ratio (V/C) (p < 0.05). At the molecular level, FMT significantly downregulated the expression of pro-inflammatory cytokines (IL-1β, IL-1α, TNF-α) and upregulated key tight junction proteins (Occludin, Claudin-1, ZO-1) and mucin-2 (MUC2) relative to the HDG (p < 0.05). 16S rRNA analysis demonstrated that FMT substantially increased the abundance of beneficial genera such as Lactobacillus and Bifidobacterium while reducing opportunistic pathogens including Romboutsia (p < 0.05). Furthermore, alpha diversity indices (Chao1 and ACE) were significantly higher in the FMT group than in all other groups (p < 0.05), indicating enhanced microbial richness and community stability. Functional prediction using PICRUSt2 revealed that FMT-enriched metabolic pathways (particularly those associated with SCFA production) and enhanced gut barrier-related functions. Collectively, this study deepens our understanding of host–microbe interactions under HFD-induced metabolic stress and provides mechanistic insights into how FMT restores gut homeostasis, highlighting its potential as a therapeutic strategy for diet-induced dysbiosis and associated metabolic disorders. Full article

The escalating incidence of colorectal cancer (CRC), particularly the alarming rise in early-onset cases, necessitates a paradigm shift from a purely genetic perspective to a broader investigation of promising pathways. This review explores the “nutri-epigenetic” interface, positioning liquid biopsy as a critical technology for translating dietary impacts into actionable clinical biomarkers. We contrast the molecular consequences of the Western dietary pattern, characterized by methyl-donor deficiency and pro-inflammatory metabolites, with the protective mechanisms of the Mediterranean diet. Mechanistically, we detail how Western-style diets drive a specific “epigenetic double-hit”: promoting global DNA hypomethylation (destabilizing LINE-1) while paradoxically inducing promoter hypermethylation of critical tumour suppressors (MLH1, APC, MGMT) and silencing tumour-suppressive microRNAs (miR-34b/c, miR-137) via methylation of their encoding genes. Conversely, we highlight the capacity of Mediterranean bioactive compounds (e.g., resveratrol, curcumin, butyrate) to inhibit DNA methyltransferases and restore epigenetic homeostasis. Bridging molecular biology and clinical utility, we demonstrate how these diet-sensitive signatures, specifically circulating methylated DNA and dysregulated microRNAs, can be captured via liquid biopsy. We propose that these circulating analytes serve as dynamic, accessible biomarkers for monitoring the molecular progression toward a carcinogenic state, thereby establishing a novel framework for personalized risk stratification and validating the efficacy of preventive nutritional strategies. Full article

Biological aging disrupts liver–gut intercommunication, resulting in the development of insulin resistance and type 2 diabetes, coupled with the imbalance of gut microbiome composition known as gut dysbiosis. Fermented red ginseng (FRG) is a renowned functional food substance showing its notable anti-inflammatory and anti-diabetic effects owing to its unique bioactive compounds known as ginsenosides. However, whether FRG could impact biological aging and age-related metabolic dysfunction is still unclear. The current study aimed to determine the health benefits of FRG in improving age-associated impaired insulin homeostasis and gut dysbiosis in 19-month-old male mice. Mice were fed with a normal chow diet (NCD) or NCD with FRG (300 mg/kg) for 14 weeks. FRG supplementation significantly improved insulin homeostasis by activating the hepatic protein kinase B (AKT) and proline-rich AKT substrate of 40 kDa (PRAS40). We also observed suppressed mRNA expression of proinflammatory cytokines and diminished inflammatory infiltrates in the liver of FRG-fed mice compared with NCD-only controls. Furthermore, alongside a decreased ratio of Firmicutes to Bacteroidetes, FRG administration enriched beneficial genera, including Muribaculaceae, Borkfalkiaceae, Parasutterella, and Clostridia vadin BB60 group, whereas FRG reduced the abundance of Erysipelotrichaceae and Dubosiella at the genus level. In summary, we suggest that FRG can be a potential anti-aging dietary supplement to manage age-driven dysregulation of insulin homeostasis and gut microbiota composition. Full article

Background/Objectives: Unhealthy lifestyles lead to chronic low-grade inflammation, increasing the risk of colorectal cancer. Few studies in East Asia have examined the association between the dietary inflammation potential and colorectal cancer incidence. Therefore, we aimed to investigate this association further in the Japanese population. Methods: This study included 38,807 men aged 45–74 years who participated in the Japan Public Health Center-based prospective study (JPHC Study). The energy-adjusted dietary inflammatory index (E-DII) was derived from a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. Differences in risk due to a combination of E-DII and lifestyle were examined using interaction term. Results: During 14 years of follow-up, 1415 colorectal cancer cases occurred. A tendency to increased colorectal cancer risk was observed with consumption of pro-inflammatory diets among Japanese men (adjusted HR [95% CI] for the highest quintile: 1.20 [0.99–1.46], p trend = 0.08), with a significantly increased risk of colon cancer (HR: 1.28 [1.01–1.63], p trend = 0.03). A possible interaction was observed with alcohol consumption (p = 0.07), which was statistically significant for proximal colon cancer (HR: 1.14 [1.05–1.25] in drinkers; p interaction = 0.01). No significant interactions with other lifestyle factors were found. Conclusions: Consumption of pro-inflammatory diets increases colorectal cancer risk among Japanese men; alcohol consumption further increases this risk for drinkers. These findings suggest that colorectal cancer may be prevented through dietary modification. Full article

Celiac disease (CeD) is a chronic immune-mediated enteropathy triggered by dietary gluten in genetically predisposed individuals which also entails intestinal dysbiosis. This hallmark microbial imbalance provides a rationale for exploring interventions that could modulate the gut ecosystem. Cocoa is a bioactive food rich in polyphenols, theobromine, and fiber, compounds known to have an influence on both immune function and gut microbiota composition. Here, we investigated the effects of cocoa supplementation on the gut microbial profile and predicted functionality in DQ8-D^d-villin-IL-15tg mice, genetically predisposed to CeD. Animals were assigned to a reference group receiving a gluten-free diet (GFD), a gluten-containing diet group (GLI), or the latter supplemented with defatted cocoa (GLI + COCOA) for 25 days. The cecal microbiota was analyzed via 16S rRNA sequencing, and functional pathways were inferred using PICRUSt2. Goblet cell counts and CeD-relevant autoantibodies were measured and correlated with microbial taxa. Cocoa supplementation partially attenuated gluten-induced dysbiosis, preserving beneficial taxa such as Akkermansia muciniphila and Lactobacillus species while reducing opportunistic and pro-inflammatory bacteria. Functional predictions suggested differences in the predicted microbial metabolic potential related to amino acid, vitamin, and phenolic compound metabolism. Cocoa also mitigated goblet cell loss and was inversely associated with anti-gliadin IgA levels. These findings suggest that cocoa, as an adjuvant to a GFD, could be of help in maintaining microbial homeostasis and intestinal health in CeD, supporting further studies to assess its translational potential. Full article

In individuals with diabetes, dysregulation of inflammatory processes hinders the progression of wounds into the proliferative phase, resulting in chronic, non-healing wounds. Total saponins from Rhizoma Panacis majoris (SRPM), bioactive compounds naturally extracted from the rhizome of Panax japonicus C.A.Mey. var. major (Burk.) C.Y.Wu and K.M.Feng, have demonstrated extensive anti-inflammatory and immunomodulatory properties. This study aims to elucidate the molecular mechanisms underlying the facilitative effects of SRPM on diabetic wound healing, with particular emphasis on its anti-inflammatory actions. A high-fat diet combined with streptozotocin (STZ) administration was used to induce type 2 diabetes in rats. After two weeks of oral treatment with SRPM suspension, a wound model was established. Subsequently, a two-week course of combined local and systemic therapy was administered using both SRPM suspension and SRPM gel. SRPM markedly reduces the levels of pro-inflammatory mediators, including IL-1α, IL-1β, IL-6, MIP-1α, TNF-α, and MCP-1, in both rat tissues and serum. Concurrently, it increases the expression of anti-inflammatory cytokines such as IL-10, TGF-β1, and PDGF-BB, while also enhancing the expression of the tissue remodelling marker bFGF. Additionally, SRPM significantly decreases the accumulation of apoptotic cells within tissues by downregulating the pro-apoptotic gene Caspase-3, upregulating the anti-apoptotic gene Bcl-2, and increasing the expression of the apoptotic cell clearance receptor MerTK. Moreover, SRPM inhibits neutrophil infiltration and the release of neutrophil extracellular traps (NETs) in tissues, promotes macrophage polarisation towards the M2 phenotype, and activates the Wnt/β-catenin signalling pathway at the molecular level. SRPM promotes the healing of wounds in diabetic rats potentially due to its anti-inflammatory properties. Full article

Obesity, an escalating global health crisis, is characterized by adipose tissue hypertrophy and chronic low-grade inflammation. Although anti-obesity drugs can induce weight loss, their use is limited by adverse effects, underscoring the need for safer therapeutic strategies. In this study, we generated a recombinant form of Trichinella spiralis-derived macrophage migration inhibitory factor (rTs-MIF) and investigated its anti-inflammatory and anti-obesity effects via immunometabolic regulation. Male C57BL/6 mice fed a 45% high-fat diet were orally administered rTs-MIF, and its effects were evaluated by measuring fat mass, glucose metabolism, serum cytokines, liver histology, and adipose tissue parameters. In 3T3-L1 cells, we examined the effects of rTs-MIF on adipocyte differentiation, obesity-related gene expression, and intracellular signaling pathways. Oral rTs-MIF suppressed body weight gain, reduced fat mass, improved glucose levels, and decreased the food efficiency ratio. It also lowered pro-inflammatory cytokines and increased markers associated with M2 macrophages. In 3T3-L1 cells, rTs-MIF inhibited adipocyte differentiation and reduced the expression of lipogenic transcription factors and mouse Mif while modulating AKT and p44/42 MAPK signaling. These findings identify rTs-MIF as a potential bioactive candidate that ameliorates obesity by regulating the immune–metabolic axis. Full article

Long-term excessive fat intake can easily induce metabolic diseases such as fatty liver and hyperlipidemia. As a natural active ingredient, polysaccharides exhibit notable lipid-lowering effects and can serve as effective lipid regulators. Nevertheless, the lipid-lowering effect of Arabica coffee cherry peel polysaccharides (CCPPs) and the underlying regulatory mechanism remain poorly understood. This study isolated polysaccharides from coffee cherry peel, and their functional properties and the lipid-lowering effects and mechanisms on hyperlipidemic mice. In high-fat diet-fed (HFD-fed) mice, CCPP administration had significant regulatory effects on various metabolic parameters. In laboratory mice where hyperlipidemia is induced by a high-fat diet, CCPP administration improved serum lipid levels and demonstrated anti-inflammatory and antioxidant effects. These benefits were achieved by reducing pro-inflammatory cytokine expression, enhancing antioxidant enzyme activity, and lowering overall oxidative stress. Additionally, it effectively decreased fat area in liver tissues and adipocytes. Specifically, compared with the control group, after high-dose CCPP intervention, the adipocyte area of mice on a high-fat diet was significantly reduced by 41.3%. Notably, CCPP intervention resulted in a shift in the gut microbiota composition. At the phylum level, the model group showed a significant increase in Bacillota and a concomitant reduction in Bacteroidetes in comparison with the control group. Compared with the model group, CCPP intervention, especially in the CCPP-H group, resulted in an increase in the proportion of Bacteroidetes and a decrease in Bacillota. At the genus level, CCPP modulated the abundances of key bacterial genera; for instance, the relative abundance of Lachnospiraceae_NK4A136_group increased from 2.64% in the model group to 11.9% in CCPP-H group, while Faecalibaculum decreased from 62.69% to 41.27% in CCPP-L group and 25.29% in CCPP-H group. These shifts suggest that CCPP has a reparative effect on the gut microbial composition, potentially contributing to the promotion of gut health. Taken together, these factors highlight the promise of CCPP as a functional food ingredient for dietary interventions to ameliorate obesity and hyperlipidemia. Full article

Background/Objectives: Given the high prevalence of obesity and abdominal obesity in Indigenous adults from Sonora (IAS) and its strong association with diet, this study evaluates the association of dietary inflammatory index (DII) with obesity and abdominal obesity and its indicators, such as body mass index (BMI) and waist circumference (WC), respectively. Methods: This cross-sectional study included data from 559 adults across two Indigenous populations (Seris and Yaquis) collected in two separate studies. Obesity and abdominal obesity were classified according to the definitions established by the World Health Organization and the International Diabetes Federation. The DII was calculated with data from population-specific food frequency questionnaires. Multiple linear regression was used to assess the association between the DII variable (expressed as both numeric and categorical) and BMI and WC, separately; multiple logistic regression was used to evaluate the association between obesity and abdominal obesity. Results: The prevalence of obesity and abdominal obesity was 34.1% and 78.2%, respectively. There was a positive association between the DII and BMI (DII as numeric: β = 0.53, p = 0.001; tertile3 of DII vs. tertile1: β = 1.86, p = 0.001) and WC (DII as numeric: β = 1.15, p = 0.002; tertile3 of DII vs. tertile1: β = 3.81, p = 0.005). Similar results were found for both types of obesity. Conclusions: Higher DII scores were associated with increased obesity indicators (BMI and WC) and a higher risk of obesity and abdominal obesity in IAS. Promoting anti-inflammatory diets represents a feasible approach for preventing non-communicable diseases. Full article