Search Results (1,635)

Background/Objectives: Hypercholesterolemia remains a major risk factor for cardiovascular disease and a leading cause of global mortality. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein receptors (LDLR), thereby reducing LDL-cholesterol (LDL-C) clearance. While monoclonal antibodies (mAbs) targeting PCSK9 are effective, their short half-life requires frequent dosing and incurs high treatment costs. This study evaluates a novel peptide-based Anti-PCSK9 product aimed at providing sustained LDL-C reduction. Methods: A novel PCSK9 based-peptide conjugated to diphtheria toxoid (DT) was evaluated in various preclinical models: high-fat diet-fed C57BL/6 mice, APOB100/hCETP transgenic mice, BALB/c mice and normocholesterolemic non-human primates. Immunogenicity (Anti-PCSK9 antibody titers, binding affinity by SPR), pharmacodynamics (LDL-C levels, inhibition of PCSK9-LDLR interaction) and safety were assessed. Toxicity was evaluated in rodents, rabbits and dogs through clinical monitoring, histopathology, organ function and safety pharmacology studies. Results: The Anti-PCSK9 product induced robust and long-lasting immune response in all models antibody titers in BALB/c mice peaked by week 6 and persisted for 12 months. LDL-C reductions of 44% in APOB100/hCETP mice and 37% in C57BL/6 mice correlated with high antibody titers and strong PCSK9-binding affinities (85 and 49 RU), leading to 59% and 58% inhibition of PCSK9-LDLR interaction, respectively. Non-human primates showed sustained responses. No systemic toxicity was observed; injection-site reactions were mild and reversible. No adverse effects were detected on cardiovascular, neurological, or respiratory systems. Conclusions: This peptide-based Anti-PCSK9 therapy offers sustained efficacy and safety, representing a promising long-acting alternative for managing hypercholesterolemia. Full article

Honeybee brood biopeptides (HBb-Bps) are a novel source of bioactive compounds with potential health benefits. In this study, HBb-Bps were conjugated with honey via a Maillard reaction and their physicochemical properties, digestive stability, antioxidant capacity, and anti-obesogenic effects were evaluated. Simulated gastrointestinal digestion revealed significantly enhanced resistance after conjugation, with the residual content increasing from 46.99% for native HBb-Bps to 86.12% for the honey-conjugated forms; furthermore, antioxidant activity was largely preserved according to the DPPH and ABTS assays. In the in vivo experiments, 30 male BrlHan: WIST@Jcl (GALAS) (Wistar) rats were fed a high-fat diet (HFD) to induce obesity and orally administered honey-conjugated HBb-Bps at doses of 200, 500, or 1000 mg/kg body weight for 16 weeks. The highest dose led to significant reductions in body weight gain, the Lee index, and body mass index. The serum lipid profiles markedly improved, with decreases in the total cholesterol, triglyceride, and LDL levels, as well as cardiovascular risk indices. Furthermore, fecal analysis showed increased levels of short-chain fatty acids, particularly butyrate. These changes suggest enhanced gut microbial activity; however, the prebiotic effects were inferred from the SCFA profiles, as the gut microbiota composition was not directly analyzed. In conclusion, honey-conjugated HBb-Bps improve gastrointestinal stability and exhibit antioxidant, hypolipidemic, and gut-modulating effects, supporting their potential use as functional ingredients for managing diet-induced metabolic disorders. Full article

(1) Objective: This study aimed to systematically elucidate the molecular mechanisms by which gypenosides (GP), a major active component of Gynostemma pentaphyllum, ameliorate hypercholesterolemia by modulating the hepatic steroidogenesis pathway, and to identify key therapeutic targets. (2) Methods: We established a high-fat diet (HFD)-induced hypercholesterolemia (HC) mouse model and performed GP intervention. An integrated multi-omics approach, combining transcriptomics and proteomics, was utilized to comprehensively analyze GP’s effects on the expression of genes and proteins associated with hepatic cholesterol synthesis, transport, and steroid hormone metabolism. (3) Results: HFD induced significant dysregulation, with 48 steroidogenesis pathway-related genes and 35 corresponding proteins exhibiting altered expression in HC mouse livers. GP treatment remarkably reversed these HFD-induced abnormalities, significantly restoring the expression levels of 42 genes and 14 proteins. Multi-omics integration identified seven critical genes/proteins—Cyp3a25, Fdft1, Tm7sf2, Hmgcs1, Fdps, Mvd, and Pmvk—that were consistently and significantly regulated by GP at both transcriptional and translational levels. Furthermore, correlation analyses demonstrated that Cyp3a25 was significantly negatively correlated with serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), whereas Fdft1, Tm7sf2, Hmgcs1, Fdps, Mvd, and Pmvk showed significant positive correlations. (4) Conclusions: GP effectively ameliorates cholesterol dyshomeostasis through a multi-targeted mechanism in the liver. It inhibits endogenous cholesterol synthesis by downregulating key enzymes (Hmgcs1, Fdft1, Pmvk, Mvd, Fdps, Tm7sf2), promotes cholesterol efflux and transport (upregulating Abca1, ApoB), and accelerates steroid hormone metabolism (upregulating Cyp3a11, Cyp3a25). These findings provide robust scientific evidence for the development of GP as a safe and effective novel therapeutic agent for hypercholesterolemia. Full article

Diseases such as obesity and metabolic-dysfunction-associated fatty liver disease (MAFLD) are often associated with changes in gut microbiota composition. The present study aims to investigate the relationship between the potential preventive effects of an Opuntia ficus-indica var. colorada cactus pulp extract on obesity and hepatic steatosis, and changes in gut microbiota composition, in a murine model fed a high-fat high-fructose diet. The low-dose extract was the most effective in reducing hepatic TG (−12.5%) and the weight of subcutaneous and visceral adipose tissue (−18.4% and 11.4%, respectively), while the high dose led to improved serum lipid profile (−74.2% in TG, −37.2% in total cholesterol, −50.5% in non-HDL cholesterol and +71.7% in HDL cholesterol). Opuntia extract supplementation did not prevent the dysbiosis in gut microbiota produced by the high-fat high-fructose diet. However, modifications in its composition, consistent with an increment in both Adlercreutzia muris and Cutibacterium acnes, and a reduction in Massiliimalia timonensis, were observed. It can be proposed that these changes may contribute to the extract effects against obesity and liver steatosis. Nevertheless, further research is required to establish a direct link between the anti-obesity and anti-steatotic effects and the functionality of the bacteria modified by the treatment. Full article

Obesity and associated metabolic disorders are rising globally, necessitating effective dietary strategies. CKDB-322, a formulation containing Lactiplantibacillus plantarum Q180 and Phaeodactylum tricornutum, was evaluated for anti-obesity efficacy using in vitro adipocyte differentiation and in vivo high-fat-diet (HFD)-induced obese mouse models. In 3T3-L1 cells, CKDB-322 suppressed adipogenesis by downregulating PPARγ and C/EBPα and enhancing glycerol release. In mice, 8 weeks of oral administration—particularly at the CKDB-322-M dose—significantly reduced body weight gain, adiposity, and serum glucose, triglyceride, and cholesterol levels without affecting liver function. Gene expression analysis revealed the strong inhibition of lipogenic markers (SREBP-1c, ACC, and FAS) in addition to activation of the fatty acid oxidation (CPT-1α and PPARα) and energy metabolism (PGC-1α and AMPK) pathways, with the most pronounced effects in the CKDB-322-M group, which also exhibited the greatest reduction in leptin. These molecular effects were confirmed histologically by decreased adipocyte hypertrophy and ameliorated hepatic steatosis. Collectively, these findings demonstrate that CKDB-322 exerts lipid-modulatory effects through multiple pathways, supporting its potential as a novel functional dietary ingredient for obesity and metabolic disorder prevention. Full article

Background: Obesity-associated liver dysfunction is a key feature of metabolic syndrome. Marine by-products, such as fish oils, offer promising dietary interventions. In this study, we aimed to assess the anti-obesity and hepatoprotective effects of herring–saury by-product-derived fermented fish oil—Gwamegi oil (GmO)—and the same oil fermented with Lactobacillus brevis KCCM13538P (GmOLb) in a high-fat-diet (HFD)-induced obese mouse model. Methods: GmO was extracted and fermented. Anti-obesity and hepatoprotective effects were assessed using in vitro and in vivo studies. For the in vivo study, female C57BL/6J mice were fed an HFD supplemented with lard (control), GmO, or GmOLb for 60 days. Metabolic and liver function parameters were assessed. Results: In 3T3-L1 adipocytes, GmOLb significantly reduced lipid accumulation and intracellular triglyceride (TG) levels compared with GmO. In HFD-fed mice, GmOLb significantly reduced body weight gain, ovarian fat mass, serum TG, low-density lipoprotein cholesterol, leptin concentration, atherogenic indices, and cardiac risk factor ratio. Furthermore, it reduced liver damage indicators, including alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels. Conclusions: Fermenting herring–saury oil with L. brevis KCCM13538P enhanced its anti-obesity and hepatoprotective effects in HFD-fed mice. GmOLb shows strong potential as a functional dietary lipid for preventing and managing metabolic disorders. Full article

This research assessed the efficacy of glutamate (Glu) supplementation to feed in counteracting growth restriction and intestinal stress-induced injury in juvenile groupers (Epinephelus coioides; initial weight 15.11 ± 0.03 g). The study comprised five isonitrogenous and iso-lipidic diets: a fish-meal-based (FM) diet, a soya-meal-based (SBM) diet, and SBM diets containing varying Glu levels of 1.0% (G-1), 2.0% (G-2), or 3.0% (G-3). The trial employed a randomized design with five treatment groups. Each group was housed in triplicate aquariums and received assigned diets for 56 consecutive days. Supplementation with Glu resulted in dose-dependent enhancements in weight gain, specific growth rate, serum high-density lipoprotein cholesterol, intestinal superoxide dismutase activity, digestive enzyme activity (trypsin, lipase, amylase), amino acid metabolic enzyme activity (glutaminase, GLS; glutamine synthetase), and intestinal mRNA levels of GLS, IL-10, and TGF-β1. Maximal values of the G-3 diet were restored to the levels of the FM diet (p > 0.05). Serum total cholesterol, intestinal total antioxidant capacity, and catalase activity followed a similar increasing trend with Glu level, attaining maxima in diet G-3, yet these values remained markedly lower than those of the FM diet (p < 0.05). Conversely, intestinal malondialdehyde content and mRNA levels of genes IL-8, IL-12, IL-1β, and TNF-α exhibited a significant dose-dependent decrease, reaching minimal levels in diet G-3 that were restored to the levels of the FM diet (p > 0.05). The results above demonstrate that Glu addition enhances nutritional status and intestinal structural integrity by augmenting antioxidant and digestive capacity and mitigating inflammatory responses, consequently enhancing growth performance and intestinal health. Full article

The present study was conducted to evaluate the individual and combined effects of dietary crude protein levels and magnetic water treatment on the growth performance, water quality, body composition, physiological responses, and immunity of Oreochromis niloticus. Using a 3 × 2 factorial design, three levels of dietary crude protein (25%, 30%, and 35%) and two water types (magnetized and non-magnetized) were tested. A total of 180 juvenile tilapia (average initial weight: 4.13 ± 0.004 g) were randomly assigned to six treatment groups and reared for 10 weeks. Results showed that magnetic water treatment significantly improved dissolved oxygen and pH, while reducing ammonia, nitrite, and nitrate concentrations. Growth performance indicators, including final weight, specific growth rate, feed conversion ratio, and average daily gain, were significantly improved by both magnetic water and increased dietary protein. Carcass crude protein content improved with both the higher dietary protein level and magnetic water, while lipid content decreased. Liver and kidney function indicators (AST, ALT, ALP, and urea) were significantly improved by magnetic treatment and higher protein levels. Blood biochemical markers (TP, ALB, and GLO) were elevated, while glucose, cholesterol, and triglycerides were reduced by magnetic water; significant interactions were observed for globulin, triglycerides, and total protein. Antioxidant enzyme activities (SOD, CAT, and GPx) increased, and MDA decreased in response to magnetic water and high-protein diets. Similarly, digestive enzyme activities (lipase, protease, and amylase) and immune parameters (IgM and lysozyme) were significantly improved, with the best values recorded in the 35% protein + magnetic water group. In conclusion, magnetic water treatment and dietary protein level independently and interactively affect the physiological performance and health of Nile tilapia, with the best outcomes obtained at 35% protein under magnetic water conditions. Full article

The objective of the study was to investigate the effects of low-protein amino acid-balanced (LPAB) diets supplemented with Astragalus polysaccharides (APSs) on the production performance, antioxidants, immunity, and biochemical index of laying hens in an elevated-temperature environment. Fifty-two-week-old Hy-Line Brown chickens (n = 768) were randomly divided into four groups, with eight replicates of 24 hens each. The control group was kept at 24 °C with a basal diet (CON), while the treatment groups were exposed to 32 °C and given the following diets: basal (HB), LPAB (HL), and LPAB with 0.5% APSs (HLA). Under heat stress, APSs increased the egg production rate and number of small white follicles, improved the yolk color, and lowered the feed conversion ratio. LPAB diets increased follicle-stimulating hormone, antioxidant enzyme activities, and anti-inflammatory cytokine activity and up-regulated related genes, whereas they reduced stress-related hormones, malondialdehyde concentrations, and triglyceride concentrations and down-regulated related genes. The addition of APSs enhanced immunoglobulin concentrations and cholesterol recovery and altered the expression of related genes. The study found that the adverse effects of high temperatures are directly related to oxidative stress. LAPB diets and APSs relatively alleviate these adverse effects. Therefore, the importance of feeding strategies such as LPAB diets and APSs for laying hens under heat stress conditions has been identified. Full article

Background: Artocarpus heterophyllus, familiar as jackfruit, is a tropical fruit highly valued not only for its nutritional content but also for its medicinal properties, including potential antidiabetic effects. Objectives: This study aimed to evaluate the insulinotropic, β-cell proliferative and anti-hyperlipidaemic properties of the ethanol extract of unripe Artocarpus heterophyllus (EEAH) in high-fat-fed (HFF) diet-induced obese mice. Method: We evaluated acute insulin secretion and β-cell proliferation in BRIN-BD11 cells, and assessed in vitro glucose diffusion and starch digestion. In vivo, acute and chronic studies in HFF induced obese mice measured glucose tolerance, body weight, food and fluid intake, and lipid profiles. A preliminary phytochemical screening was also performed. Results: In this study, EEAH exhibited significant antidiabetic activity through multiple mechanisms. EEAH enhanced glucose-stimulated insulin secretion in BRIN-BD11 β-cells via K_ATP channel modulation and cAMP-mediated pathways, with partial dependence on extracellular calcium, and it also promoted β-cell proliferation. In vitro assays revealed its ability to inhibit starch digestion and glucose diffusion, indicating delayed carbohydrate digestion and absorption. In high-fat-fed (HFF) obese mice, the acute and chronic oral administration of EEAH improved oral glucose tolerance, reduced fasting blood glucose, decreased body weight, and normalized food and fluid intake. Lipid profile analysis showed increased HDL and reduced total cholesterol, LDL, and triglycerides, while higher doses of EEAH also enhanced gut motility. Phytochemical screening revealed the presence of bioactive compounds such as alkaloids, tannins, flavonoids, saponins, steroids, and terpenoids, which are likely responsible for these therapeutic effects. Conclusion: These findings highlight EEAH as a promising natural candidate for adjunctive therapy in managing type 2 diabetes and associated metabolic disorders and emphasize the importance of future multi-omics studies to elucidate its molecular targets and pathways. Full article

Asimina triloba (pawpaw), a member of the Annonaceae family, contains various bioactive phytochemicals, including alkaloids, polyphenols, and acetogenins. In this study, the effects of pawpaw seed extract (PSE) on obesity and plasma lipid concentrations were investigated in mice with high-fat diet (HFD)-induced obesity. Male C57BL/6J mice were fed a normal diet (ND) or an HFD for two weeks. The mice in the latter group were then divided into three groups: HFD, L-PSE, and H-PSE. Following a two-week adaptive period, the L-PSE and H-PSE groups were fed an experimental diet containing 250 mg and 500 mg PSE/kg of HFD, respectively, for two weeks. Mice in the HFD group exhibited significantly higher body weights than that of mice in the ND group. A significant decrease in body weight was observed in the H-PSE group compared with that in the HFD group. The perirenal, testicular, and total visceral fat masses of the mice in the H-PSE group were consistently lower than those of the mice in the HFD group. Administration of high-dose PSE decreased the expression of Fasn (encoding fatty acid synthase) and Dgat2 (encoding diglyceride acyltransferase 2) in testicular fat tissues. However, PSE administration did not decrease blood glucose and plasma cholesterol levels compared with that in the HFD group. These findings suggest that the administration of PSE suppresses HFD-induced obesity in mice, while its hypoglycemic or cholesterol-lowering actions are less pronounced. Full article

The efficacy of Lagerstroemia speciosa (banaba) leaf extract (BLE), policosanol (POL), and their combination (BLE+POL) was evaluated in zebrafish (Danio rerio) against high cholesterol (HC)- and galactose (HG)-induced metabolic stress and organ toxicity. After 12 weeks of dietary intervention, BLE+POL significantly reduced HC+HG-augmented weight gain and improved hepatic and nephromegaly. Compared with BLE or POL alone, the combined intake of BLE+POL more effectively alleviated dyslipidemia and blood glucose levels. Likewise, BLE+POL effectively reduced blood malondialdehyde (MDA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels and boosted plasma sulfhydryl content, ferric ion reduction ability (FRA), and paraoxonase (PON) activity. Histological outcomes suggest that BLE+POL has higher efficacy than either BLE or POL in mitigating HC+HG-induced fatty liver changes, hepatic inflammation, kidney senescence, and reactive oxygen species (ROS) production. Consistently, BLE+POL augmented the spermatozoa counts in the testes, enhanced mature vitellogenic oocytes in ovaries, and protected them from the HC+HG-induced oxidative stress. Compared with either BLE or POL, a combined intake of BLE+POL displayed a superior effect in inhibiting the apoptosis and accumulation of lipid peroxidation species 4-hyrdoxynonenal (4-HNE) in the brain. A combined intake of BLE+POL exhibited a pronounced impact than the BLE and POL alone and can be utilized as an effective formulation to counteract the HC+HG-induced events. Full article

Cardiovascular disease (CVD) and dementia may share common pathogenic factors such as atherosclerosis and hyperlipoproteinemia. Dyslipidemia-induced oxidative stress contributes to dementia comorbidity in CVD. Abelmoschus esculentus (AE, okra) potentiates in alleviating hyperlipidemia and diabetes-related cognitive impairment. This study evaluated the effects of AE in hyperlipidemic ApoE^−/− mice treated with streptozotocin (50 mg/kg) and fed a high-fat diet (17% lard oil, 1.2% cholesterol). AE fractions F1 or F2 (0.65 mg/kg) were administered for 8 weeks. AE significantly reduced serum LDL-C, HDL-C, triglycerides, and glucose, improved cognitive and memory function, and protected hippocampal neurons. AE also lowered oxidative stress markers (8-hydroxy-2′-deoxyguanosine, 8-OHdG) and modulated neuronal nuclei (NeuN) and doublecortin (DCX) expression. In vitro, AE promoted neurite outgrowth and neuronal differentiation in retinoic acid (RA)-differentiated human SH-SY5Y cells under metabolic stress (glucose and palmitate), alongside the upregulation of heme oxygenase-1 (HO-1), Nuclear factor-erythroid 2-related factor 2 (Nrf2), and brain-derived neurotrophic factor (BDNF). These findings suggest AE may counter cognitive decline via oxidative stress regulation and the enhancement of neuronal differentiation. Full article

Chrysanthemum × morifolium (Ramat) Hemsl. (Hangbaiju), which has been widely consumed as a herbal tea for over 3000 years, is renowned for its biosafety and diverse bioactivities. This study investigates the impact of polyphenol-rich Hangbaiju extracts (HE) on high-fat diet-induced obesity in mice. HE contains phenolic acids and flavonoids with anti-obesity properties, such as apigenin, luteolin-7-glucoside, apigenin-7-O-glucoside, kaempferol 3-(6″-acetylglucoside), etc. To establish the obesity model, mice were randomly assigned into four groups (n = 8 per group) and administered with either HE or water for 42 days under high-fat or low-fat dietary conditions. Administration of low (LH) and high (HH) doses of HE both significantly suppressed body weight growth (by 16.28% and 16.24%, respectively) and adipose tissue enlargement in obese mice. HE significantly improved the serum lipid profiles, mainly manifested as decreased levels of triglycerides (28.19% in LH and 19.59% in HH) and increased levels of high-density lipoprotein cholesterol (44.34% in LH and 54.88% in HH), and further attenuated liver lipid deposition. Furthermore, HE significantly decreased the Firmicutes/Bacteroidetes ratio 0.23-fold (LH) and 0.12-fold (HH), indicating an improvement in the microecological balance of the gut. HE administration also elevated the relative abundance of beneficial bacteria (e.g., Allobaculum, norank_f__Muribaculaceae), while suppressing harmful pathogenic proliferation (e.g., Dubosiella, Romboutsia). In conclusion, HE ameliorates obesity and hyperlipidemia through modulating lipid metabolism and restoring the balance of intestinal microecology, thus being promising for obesity therapy. Full article

Background/Objectives: Conventional ketogenic diets, although effective for weight loss, often contain high total and saturated fat intake, which leads to increased low-density lipoprotein cholesterol (LDL-C). Thus, the Healthy Ketogenic Diet (HKD) was developed to address these concerns. It emphasizes calorie restriction, limiting net carbohydrate intake to 50 g per day, prioritizing unsaturated fats, and reducing saturated fat intake. However, adherence to the HKD remains a challenge in urban, time-constrained environments. Therefore, this pilot randomized controlled trial aimed to investigate the effects of Healthy Ketogenic Diet Ready-To-Eat (HKD-RTE) meals (provided for the first month only) versus HKD alone on weight loss and metabolic parameters among overweight adults. Methods: Multi-ethnic Asian adults (n = 50) with a body mass index (BMI) ≥ 27.5 kg/m² were randomized into the HKD-RTE group (n = 24) and the HKD group (n = 26). Both groups followed the HKD for six months, with the HKD-RTE group receiving HKD-RTE meals during the first month. Five in-person workshops and mobile health coaching through the Nutritionist Buddy Keto app helped to facilitate dietary adherence. The primary outcome was the change in body weight at 6 months. Linear regression was performed on the change from baseline for each continuous outcome, adjusting for demographics and relevant covariates. Logistic regression was performed on binary weight loss ≥ 5%, adjusting for demographics and relevant covariates. Results: In the HKD group, participants’ adherence to the 50 g net carbohydrate target was 15 days, while that in the HKD-RTE group was 19 days over a period of 30 days. Participants’ adherence to calorie targets was 21 days in the HKD group and 23 days in the HKD-RTE. The average compliance with the HKD-RTE meals provided in the HKD-RTE group was 55%. The HKD-RTE group experienced a greater percentage weight loss at 1 month (−4.8 ± 3.0% vs. −1.8 ± 6.2%), although this was not statistically significant. This trend continued up to 6 months, with the HKD-RTE group showing a greater percentage weight reduction (−8.6 ± 6.8% vs. −3.9 ± 8.6%; p = 0.092). At 6 months, the HKD-RTE group had a greater reduction in total cholesterol (−0.54 ± 0.76 mmol/L vs. −0.05 ± 0.56 mmol/L; p = 0.283) and LDL-C (−0.43 ± 0.67 mmol/L vs. −0.03 ± 0.52 mmol/L; p = 0.374) compared to the HKD group. Additionally, the HKD-RTE group exhibited greater reductions in systolic blood pressure (−8.3 ± 9.7 mmHg vs. −5.3 ± 11.0 mmHg), diastolic blood pressure (−7.7 ± 8.8 mmHg vs. −2.0 ± 7.0 mmHg), and HbA1c (−0.3 ± 0.5% vs. −0.1 ± 0.4%) than the HKD group (not statistically significant for any). Conclusions: Both HKD-RTE and HKD led to weight loss and improved metabolic profiles. The HKD-RTE group tended to show more favorable outcomes. Short-term HKD-RTE meal provision may enhance initial weight loss, with sustained long-term effects. Full article