Search Results (2,600)

The prevention and treatment of cardiovascular disease (CVD) are undergoing a paradigm shift from a lipid-centric approach to a holistic metabolic perspective. Central to this evolution is the gut–fat–heart axis, a sophisticated three-dimensional communication network that integrates neural, endocrine, and immunometabolic signaling to regulate systemic lipid homeostasis. This manuscript systematically explores how the gut microbiota acts as a “metabolic organ” to remotely control host health through the production of bioactive metabolites and the modulation of molecular communication networks. At the physiological level, microbial products such as short-chain fatty acids (SCFAs) and modified bile acids regulate energy balance and lipid synthesis via the FXR-FGF15/19 axis and G protein-coupled receptors. Furthermore, gut hormones like GLP-1 and neuro-reflex pathways involving the vagus nerve provide rapid control over postprandial lipid clearance and feeding behavior. Conversely, pathological dysbiosis triggers the accumulation of harmful metabolites, such as trimethylamine N-oxide (TMAO) and lipopolysaccharides (LPS), which drive lipotoxicity, vascular inflammation, and “dysfunctional HDL” formation. These processes accelerate the progression of atherosclerosis, heart failure, and metabolic syndrome. Finally, the article outlines promising clinical translation strategies, including the development of TMA lyase inhibitors, next-generation probiotics, and the use of phytochemicals to reshape the microbial landscape. By decoding the molecular dialogues within the gut–fat–heart axis, this research provides a novel strategic vantage point for the integrated management of cardiovascular–kidney–metabolic (CKM) syndrome. Full article

In addition to its role in energy storage, adipose tissue contributes substantially to energy metabolism, endocrine regulation, and inflammatory processes. Sujiang pigs, a hybrid breed approved by the National Livestock and Poultry Genetic Resources Committee of China as a new national breed in 2013, possess a genetic predisposition for substantial fat deposition, making them an ideal model for investigating the mechanisms underlying adipose tissue accumulation. In this study, back fat (BF; subcutaneous adipose tissue), greater omentum (GOM; visceral adipose tissue), and mesenteric adipose tissue (MAD; visceral adipose tissue) were collected from three 6-month-old male Sujiang pigs for RNA-seq analysis. Comparative analyses identified 3005 differentially expressed genes (DEGs) between BF and GOM, 975 DEGs between BF and MAD, and 892 DEGs between GOM and MAD. To validate the reliability of the sequencing data, five DEGs were randomly selected for RT-qPCR verification. The DEGs were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. By integrating protein–protein interaction (PPI) networks with bioinformatics analyses, we identified candidate genes potentially associated with lipid metabolism (e.g., WNT9A, WNT5A, and PDGFRA) and inflammatory responses in adipose tissue (e.g., CSF1R, C1QB, and CD4). These findings indicate potential molecular differences between porcine visceral and subcutaneous adipose tissues and may serve as a reference for further studies on the molecular regulation of adipose tissue metabolism. Full article

Regenerative medicine integrates interdisciplinary approaches towards restoring the function of diseased organs. This study examined alterations that occurred in the liver under a high-fat diet (HFD) with the development of obesity and fatty liver, and changes in metabolic homeostasis and glucose levels, in mice. HFD nutrition causes hyperglycemia, leading to the formation and accumulation of advanced glycation end-products (AGEs) promoting protein post-translational modifications (PTMs) and introducing crosslinking in the extracellular matrix (ECM). Using histological and gene expression analyses, we detected an increase in adiposity, as well as in ECM protein deposition in the liver. Further, decellularization of the liver yielded the isolated ECM organ scaffold, allowing us to analyze the chemical modification in proteins by various imaging methods combined with spectroscopy. The measurements of intrinsic protein fluorescence are consistent with increased AGE-associated levels. SEM allows for the visualization of ECM fiber thickening as a result of protein crosslinking. Using cathodoluminescence, a label-free imaging method, we confirmed the protein modifications. The combination of innovative technologies highlights the ECM structural alterations associated with impaired glucose regulation and liver adiposity. These findings provide novel views on liver-scaffold ECM structure under metabolic diseases that will play a significant role in accelerating the understanding of effective regenerative therapies. Full article

Dysregulated lipid metabolism is a core pathogenic driver of type 2 diabetes. Honokiol (HKL), the major bioactive constituent of Magnolia officinalis, possesses anti-diabetic and lipid-regulatory properties. However, the underlying molecular mechanism remains elusive. This study investigates how HKL ameliorates high-glucose/high-fat (HGHF)-induced hepatic lipid accumulation, with a focus on the role of SIRT3-mediated deacetylation of peroxisome proliferator-activated receptor γ (PPARG). The core targets of HKL were identified through network pharmacology and molecular docking. Human hepatic MIHA cells were treated with glucose (Glu, 40 mM) and palmitic acid (0.2~0.3 mM PA) to establish a lipid accumulation model, followed by treatment with HKL (5–10 μM) with or without a confirmed selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). Lipid accumulation was assessed by Oil Red O staining and by measuring triglyceride (TG) and total cholesterol (TC) levels. Protein expression and the SIRT3-PPARG interaction were analyzed by Western blot and co-immunoprecipitation (Co-IP). SIRT3 and PPARG were identified as core targets of HKL, exhibiting strong binding with calculated energies of −6.834 and −6.579 kcal/mol, respectively. In MIHA cells, HGHF (40 mM Glu + 0.2–0.3 mM PA) induced lipid accumulation, including increased lipid droplets, and elevated TG (2.5–3.2-fold) and TC (2.2–2.8-fold) contents in a dose-dependent manner, accompanied by downregulated SIRT3/PPARG expression and heightened global protein acetylation. The non-cytotoxic HGHF-M condition (40 mM Glu + 0.2 mM PA) was selected for further experiments. HKL (5–10 μM) dose-dependently reduced lipid accumulation by ~38–60%, decreased TG and TC levels by up to ~13% and ~30%, and restored SIRT3/PPARG expression. The protective effects of HKL were reversed by inhibition of SIRT3 with 3-TYP. Co-IP confirmed the interaction between SIRT3 and PPARG, and SIRT3 overexpression significantly decreased the acetylation level of PPARG. This study suggests that HKL ameliorates hepatic lipid accumulation via SIRT3-mediated deacetylation of PPARG, providing an experimental basis for considering HKL as a potential therapeutic agent against metabolic disorders. Full article

The fruit of Crataegi fructus (CF) is a traditional “medicine food” herb widely used for its lipid-lowering properties, but its active ingredients and mechanisms against metabolic dysfunction-associated fatty liver disease (MAFLD) remain poorly understood. This study employed an integrated multi-omics approach, combining serum metabolomics, liver transcriptomics, weighted gene co-expression network analysis (WGCNA), network pharmacology, and molecular docking, to systematically investigate the effects of CF extract (CFE) in a high-fat diet (HFD)-induced mouse model of MAFLD. Our analysis revealed that CFE treatment significantly reduced body weight gain (p < 0.01), improved glucose tolerance and insulin sensitivity (p < 0.01), and alleviated hepatic steatosis, as evidenced by reduced lipid accumulation and decreased NAS scores (p < 0.001). Metabolomics analysis showed that CFE reversed HFD-induced disturbances in serum fatty acids, glycerophospholipids, and bile acid metabolites. Transcriptomics further revealed that the AMPK and PPAR signalling pathways were critically involved in the regulation of lipid metabolism by which CFE alleviated MAFLD. Consistently, CFE treatment resulted in significant upregulation of AMPK and PPARα expression (p < 0.001) and downregulation of CD36 and DPP4 (p < 0.001), as confirmed by Western blotting and qPCR. Furthermore, integration of WGCNA and network pharmacology pinpointed chlorogenic acid (CA), ursolic acid (UA), and oleanolic acid (OA) as the primary bioactive components, and their lipid-lowering effects were validated in FFA-treated THLE-2 cells. In conclusion, this study offers preliminary insights into the lipid-lowering mechanisms of CFE via regulation of the AMPK/PPARα/CD36/DPP4 signalling pathway and support its further development as a functional food ingredient for MAFLD prevention. Full article

This study proposes a vision-based framework for automated inspection and quality grading of beef steaks by integrating fat marbling distribution analysis and lean-meat color evaluation. In frozen beef products, surface frost often generates specular reflections that resemble both fat and lean regions, thereby reducing segmentation accuracy. To address this challenge, a sequential and interpretable analytical framework is developed. First, homomorphic filtering is applied to suppress frost-induced illumination artifacts, followed by curvelet transform combined with square-ring filtering to separate fat and lean regions based on their multi-scale and directional characteristics. For marbling analysis, the convex hull, skeleton, and principal axis of the steak are extracted, and a chi-square goodness-of-fit test is performed within eight predefined regions to quantitatively evaluate marbling distribution uniformity and identify localized fat accumulation. For lean-meat evaluation, RGB color features are extracted and classified using a Support Vector Machine (SVM) to determine redness levels. The resulting marbling and color information are subsequently integrated through a weighted grading strategy to estimate the final quality grade. Experimental results demonstrate a fat detection rate of 92.68%, a false-positive rate of 4.97%, and a correct classification rate of 94.09% for fat segmentation, while the SVM-based lean-meat color classifier achieves an accuracy of 96.67%. Furthermore, the proposed grading framework attains an overall grading accuracy of 90.38%, showing strong agreement with human evaluation. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global metabolic disorder. As a non-pharmacological intervention, the effects of high-intensity interval training (HIIT) on MASLD and its molecular mechanisms remain poorly understood. This study aimed to investigate whether HIIT could ameliorate high-fat diet (HFD)-induced liver fibrosis by recalibrating the intrahepatic lactate metabolic axis. Methods: An HFD-induced murine MASLD model combined with HIIT intervention was utilized to evaluate the therapeutic efficacy and underlying mechanisms. Hepatosomatic indices, histological architecture and fibrosis severity were examined. Lactate concentrations within the systemic circulation and hepatic parenchyma, alongside comprehensive lipid profiles, were measured. The expressions of genes and proteins involved in hepatic lactate metabolism were delineated via qPCR and Western blotting. Results: The 8-week HIIT intervention effectively improved liver lipid accumulation, hepatocellular injury, and oxidative stress caused by a high-fat diet. Fibrotic expansion and suppressed hepatic stellate cell activation were restricted markedly, as evidenced by the downregulation of collagen type I alpha 1 chain and alpha-smooth muscle actin(α-SMA). HIIT reversed the HFD-induced accumulation of lactate in both systemic circulation and liver tissues, which was found to positively correlate with hepatic α-SMA. Mechanistically, HIIT regulated the expression of the lactate metabolism-related proteins lactate dehydrogenase A and monocarboxylate transporter 1, while selectively enhancing the expression of the gluconeogenic enzymes. Conclusions: Our findings indicate that HIIT effectively ameliorated MASLD and associated hepatic fibrosis by remodeling the hepatic lactate metabolic axis, specifically through the suppression of lactate production and the enhancement of its clearance. These results indicate that targeting lactate homeostasis might be a promising therapeutic strategy for MASLD. Full article

Background/Objective: Highly palatable foods are pleasurable and motivational stimuli that activate the brain’s reward system and can induce overeating in the absence of physiological needs. This study investigated how different access patterns to a cafeteria diet influence food intake, body weight-related parameters, and metabolic and neurobehavioral outcomes. Methods: At postnatal day 31, forty male Wistar rats were assigned to a standard diet or a cafeteria diet with continuous, predictable intermittent, or unpredictable intermittent access. After 10 weeks, the open-field and sucrose-preference tests assessed exploratory and anxiety-like behaviors and reward-related responses, respectively. Body composition, serum biochemical parameters, neurotransmitter content, and mRNA and protein levels were analyzed in reward-related brain regions. Results: Intermittent access increased food intake on cafeteria days compared with continuous access, with unpredictable access yielding the highest intake. Continuous-access rats exhibited higher final body weight and fat accumulation than chow-fed Control rats. Despite similar body weight, both intermittent-access groups had higher visceral adiposity, obesity indices, and adverse metabolic outcomes than the Control group. All cafeteria-fed rats displayed anxiety-like behavior, and all groups preferred sucrose except the continuous-access group. Molecular analyses revealed region-specific differences in gene expression related to neuroplasticity, stress response, and epigenetic regulation that varied with access pattern and predictability. Conclusions: Our results suggest that, beyond diet composition, the pattern and predictability of food access are key determinants of feeding behavior. Intermittent access increases the motivational value of the cafeteria diet, promoting overeating and driving reward- and stress-related neuroadaptations with potential metabolic and mental health implications. Full article

Background: Visceral fat accumulation is strongly associated with metabolic disorders, particularly in Japanese adults who accumulate visceral fat even at lower body mass index levels. Sorghum is a whole grain rich in resistant starch and polyphenols, which may influence visceral fat area (VFA). This exploratory study aimed to investigate the effects of 12-week sorghum consumption on VFA and metabolic parameters in Japanese adults with visceral fat accumulation. Methods: This single-arm intervention trial included adults aged 20–60 years with VFA ≥ 100 cm² and no ongoing medical treatment. Participants consumed cooked sorghum (80 g/day, dry weight) for 12 weeks. Anthropometric variables, VFA, blood pressure, and blood biomarkers were assessed before and after the intervention. Dietary intake was evaluated using a three-day food record. Pre- and post-intervention values were compared using paired t-tests. Results: Nine participants completed the study. VFA significantly decreased after 12 weeks of sorghum consumption (p = 0.02). Alanine aminotransferase (ALT) levels showed a non-significant reduction, while other metabolic and hepatic biomarkers remained stable. No adverse changes were observed in dietary intake or physical activity. Eight of nine participants exhibited reductions in VFA. Conclusions: Daily sorghum consumption may contribute to reductions in VFA and improvements in liver-related biomarkers in Japanese adults with visceral fat accumulation. These findings provide preliminary evidence that partially replacing major carbohydrate sources with sorghum may support visceral fat management. Further confirmation in randomized controlled trials is warranted. Full article

Background/Objectives: Intramuscular adipose tissue (IntraMAT) is the ectopic fat which accumulates within skeletal muscle. The relationship between trunk IntraMAT content and dietary intake was shown to differ with age in men, but it remains unclear the relationship in women. Therefore, the present study investigated the associations of IntraMAT content with dietary intake and eating behavior in younger and older women. Methods: This cross-sectional study involved 24 young women aged 18 to 23 years (body mass index (BMI): 20.5 ± 2.3 kg/m²) and 25 older women aged 66 to 77 years (BMI: 21.7 ± 2.5 kg/m²) who participated. IntraMAT content was assessed by magnetic resonance imaging at the height of the 3rd lumbar vertebra. Dietary intake was evaluated using a self-administered diet history questionnaire. Eating behavior was evaluated by scores calculated using the eating behavior questionnaire in the guideline for obesity (2022). Blood properties related to metabolic syndrome were also measured. Results: In the younger group, IntraMAT content was significantly related to HDL cholesterol and insulin (r_s = −0.411 and 0.415, p < 0.05). In the older group, IntraMAT content significantly correlated with the percentage of energy from protein, sense of hunger, and total eating behavior (r_s = −0.410 to 0.412, p < 0.05). Conclusions: Trunk IntraMAT content may be related to dietary protein intake and eating behavior in the older group. Full article

Background/Objectives: Obesity is a multifactorial chronic condition characterized by the accumulation of excess adiposity and complex interplay between intrinsic and extrinsic factors. It is an increasingly common condition, closely implicated with the incidence and progression of cardiovascular disease and its risk factors. This narrative review synthesizes and summarizes recent evidence on obesity, with a focus on the diagnosis of obesity, an exploration of both visceral and subcutaneous adipose tissue, available interventions for obesity ranging from dietary modifications to novel anti-obesity medications, and key associations with obesity and cardiovascular diseases. This review is distinct in its integrated focus on obesity definition and diagnosis, imaging modalities, the latest non-pharmacologic and pharmacologic interventions, and also the interplay between obesity and certain cardiovascular conditions as well as their risk factors. Results: The diagnosis of obesity has been evolving with the incorporation of anthropometric measurements and imaging modalities rather than simply the body mass index. There is a wide array of contributors to obesity including genetic factors, behavior, hormonal regulators, the brain–gut axis, and psychosocial stressors. Anti-obesity medications have been evolving rapidly, with current emphasis on glucagon-like peptide 1 receptor agonists. Obesity is closely implicated in cardiovascular conditions such as atherosclerotic disease, heart failure, atrial fibrillation, and hypertension as well as related risk factors such as diabetes mellitus, chronic kidney disease and sleep apnea. Conclusions: Obesity is a widely prevalent, chronic, and complex disease. The use of a variety of anthropometric measurements can help risk-stratify individuals. Imaging techniques are also helpful in evaluating body fat. Evaluating individuals from a holistic perspective is imperative to appreciate the various contributors to obesity. There are a variety of interventions available for obesity management including lifestyle interventions, bariatric surgery, and pharmacologic therapy. Notably, obesity is closely tied with cardiovascular diseases and recent pharmacologic anti-obesity agents may mitigate cardiovascular risk. Full article

Obesity is an adiposity-based low-grade chronic inflammatory disease characterized by excessive fat accumulation and/or dysregulated adipose function, affecting health, quality of life, and mortality. Despite the implementation of public health strategies and individualized therapeutic interventions, obesity currently affects more than one billion people worldwide. Although the distinction between preclinical obesity (PCO) and clinical obesity (CO) has recently been conceptually established, practical tools capable of translating this distinction into clinical diagnosis are still lacking. In this study, we proposed a novel diagnostic framework in which the SF-36 Role-Physical (RP) domain functions as a screening tool to identify physical limitations associated with CO. The framework integrates anthropometric criteria (body mass index and waist circumference), organ dysfunction (presence of comorbidities), and objectively defined physical limitations based on RP domain cutoff values. To validate the framework, patients’ inflammatory profiles were evaluated. Our results demonstrated that stratification based on this functional model could identify a phenotype characterized by a distinct pro-inflammatory profile. CO patients exhibited significantly increased IL-6 and IL-17A levels compared with the PCO and overweight groups. Taken together, these findings suggest that this approach may serve as a simple, low-cost, and clinically applicable strategy to support differentiation between preclinical and clinical obesity. However, larger longitudinal and multicenter studies are needed to validate these findings. Full article

Obesity and its metabolic complications represent a major global health challenge, and food-derived bioactive peptides are emerging as promising dietary interventions. In this study, two hemp seed protein-derived tetrapeptides with pancreatic lipase (PL) and cholesterol esterase (CE) inhibitory activity, APAM and RLPA, were co-administered with a high-fat diet (HFD) to male C57BL/6J mice at 25 and 100 mg/kg body weight for 10 weeks. Both peptides dose-dependently alleviated HFD-induced body weight gain, visceral fat accumulation, hepatic steatosis, dyslipidemia, hyperglycemia, and systemic inflammation. Mechanistically, both peptides inhibited intestinal PL and CE activities and enhanced fecal lipid excretion, supporting direct suppression of intestinal fat digestion. 16S rRNA gene sequencing revealed partial restoration of HFD-disrupted gut microbiota, with APAM preferentially enriching Bifidobacterium and Roseburia, while RLPA promoted Akkermansia and Lactobacillus, accompanied by differential improvements in fecal short-chain fatty acid (SCFA) profiles. Hepatic transcriptomics identified the PPAR signaling pathway as a shared regulatory hub, and multi-omics integration revealed significant correlations linking gut microbiota, SCFA production, hepatic gene expression, and metabolic phenotypes. These findings suggest a dual-pathway anti-obesity mechanism integrating intestinal lipid digestion inhibition with gut–liver axis modulation, and highlight hemp seed protein-derived peptides as potential functional food ingredients for obesity prevention. Full article

While amyloid precursor protein (APP) overexpression in adipose tissue is a recognized consequence of high-fat diet (HFD) feeding, its role in metabolically active organs and the mechanisms linking it to systematic dysfunction remain unclear. In particular, the potential for diet-induced APP dysregulation in the other tissues and the contribution of its βC-terminal fragment (βCTF) are poorly characterized. Using a high-fat diet (HFD) mouse model to induce systematic metabolic stress, we assessed APP and βCTF levels across multiple tissues. HFD triggered a tissue-specific response, with APP levels increasing >2-fold in visceral and subcutaneous white adipose tissue (WAT) and in the kidney but remained unchanged in the liver and brain. βCTF levels were significantly elevated in the visceral WAT (3-fold) and kidney. In these responsive tissues, APP and βCTF accumulated within mitochondria, which coincided with significantly reduced complex I and IV activities. Complementary in vitro studies confirmed that APP levels can dictate mitochondrial function. Furthermore, we identified that cytokines–IL-4, IL-13, TNF-α, and IL-1β–induced APP transcription, providing a mechanistic link between diet-induced inflammation and APP dysregulation. Collectively, our findings demonstrate that APP is overexpressed in response to HFD in select peripheral tissues, which coincides with reduced mitochondrial complex enzyme activities and increased cytokine levels. Full article

Plant-derived bioactive peptides have garnered widespread interest for their functions in managing obesity and associated metabolic disorders. This study investigated the lipid-lowering activity and underlying mechanisms of VPIIMH, a hexapeptide derived from Chlorella pyrenoids, using in vitro enzymatic assays, Caenorhabditis elegans models, and network pharmacology. In vitro, VPIIMH acted as a reversible non-competitive inhibitor of pancreatic lipase, achieving an inhibition rate of 43.17 ± 1.47% at 8.0 mg/mL. Molecular docking revealed that this inhibition likely occurs through ionic bonds between VPIIMH and PL (1LPB) at Arg256. In a high-fat C. elegans model, treatment with 0.5 mg/mL VPIIMH significantly reduced fat accumulation by 37.2% and triglyceride levels by 26.9%. Furthermore, VPIIMH extended the lifespan of C. elegans under oxidant stress by 40.3% and under heat stress by 17.5%. Network pharmacology predicted that VPIIMH targets nine core proteins, which were classified into three synergistic modules: the SIRT1-PPAR for core regulation, the RAS for systemic coordination, and the inflammatory target (CCR5, MMP9, EGFR) for microenvironment support. This study elucidates the multi-target and multi-pathway mechanism of VPIIMH, suggesting its potential application in combating obesity and related lipid metabolism disorders. These findings provide a scientific basis for the development of VPIIMH as a functional food ingredient targeting metabolic health. Full article