Search Results (139)

Background: Severe hypertriglyceridemia (SHTG) is associated with acute pancreatitis, metabolic dysfunction, and increased cardiovascular risk. Its genetic architecture ranges from rare biallelic variants causing familial chylomicronemia syndrome (FCS) to more prevalent polygenic or multifactorial chylomicronemia syndromes (MCS). Methods: We systematically reviewed scientific literature up to 2025 for studies reporting genetic data, clinical features, or therapeutic outcomes in adults with triglycerides (TG) ≥ 500 mg/dL. Extracted data were synthesized for genotype, polygenic risk score (PRS), TG levels, metabolic comorbidities, hepatic steatosis, pancreatitis, and treatment response. Results: Ten studies (n = 2521) were included. FCS due to biallelic LPL, APOC2, GPIHBP1, or LMF1 variants accounted for <5% of cases and showed extreme TG elevations (>2800 mg/dL) with pancreatitis prevalence (>70%). APOA5, APOC3, and APOB variants were associated with intermediate TG levels and high rates of metabolic dysfunction-associated steatotic liver disease (MASLD). Polygenic hypertriglyceridemia represented ~70–80% of cases, with TG ≈ 2200 mg/dL and pancreatitis prevalence 15–20%, largely modulated by metabolic triggers. MASLD was present in >70% of polygenic cases, supporting a “two-hit” model where hepatic overproduction of TG-rich lipoproteins amplifies TG excess. Interventional trials demonstrated TG reductions with APOC3 antisense therapy (70–80%) and ANGPTL3 inhibition (50–55%), while GLP-1RA significantly reduced hepatic fat (30–35%) and resolved NASH in up to 59% of patients. Conclusions: SHTG displays a genotype–phenotype gradient: FCS is linked to recurrent pancreatitis, whereas polygenic/MCS forms are closely associated with MASLD and metabolic dysfunction. These findings support a precision-medicine approach integrating genetic testing and PRS-guided strategies—prioritizing APOC3/ANGPTL3 inhibitors for FCS and combined TG-lowering plus metabolic therapies for MCS—to reduce pancreatitis recurrence and liver disease. Full article

Background/Objectives: Metabolic syndrome affects half of middle-aged (ages 45–64) Hispanic or Latino (Latino) adults. Pulses, fiber-rich plant proteins common in Latino diets (e.g., dry beans and lentils), may mitigate metabolic syndrome. We evaluated the association between pulse intake and metabolic syndrome. Methods: We analyzed data from 6,958 adults aged ≥ 50 in the Hispanic Community Health Study/Study of Latinos (2008–2011) Visit 1. Pulse intake was assessed using two 24 h dietary recalls and categorized into no, low (<1/2 cup), moderate (≥1/2 to 3/4 cup), and high pulse (>3/4 cup) daily intake groups. Metabolic syndrome was defined by criteria including blood pressure ≥130/85 mmHg or medication use, triglycerides ≥150 mg/dL or medication use, high-density lipoprotein cholesterol (men <40 mg/dL and women <50 mg/dL), and waist circumference (men ≥102 cm and women ≥88 cm). We used multivariate logistic regression models with predicted probability proportions to assess the association adjusted for sociodemographic factors, acculturation, diet quality, energy intake, and physical activity. Results: Of the 6,958 participants, 53.1% had metabolic syndrome and 53.4% had a moderate or high pulse intake. Pulse intake varied, where 19.4% had a high intake, 33.9% had a moderate intake, 12.5% had a low intake, and 34.2% had no intake. Moderate (predicted marginal = 0.52, 95% confidence interval [CI] = 0.49, 0.55) and high (predicted marginal = 0.49, 95%CI = 0.45, 0.53) intakes were associated with a lower prevalence of metabolic syndrome. Conclusions: Among Latino adults ≥50 years old, a moderate or high pulse intake was associated with a lower prevalence of metabolic syndrome. Increasing the pulse intake in the population may be linked to reduced metabolic syndrome. Full article

Grape pomace, a polyphenol-rich byproduct of wine production, represents a promising source of bioactive compounds for managing diabetes and its complications. This study evaluates the effect of a novel grape pomace extract on carbohydrate and lipid metabolism, and oxidative stress in type 1 diabetes mellitus. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin. Starting on day 14 post-induction, rats received oral grape pomace extract at a dose of 45 mg of polyphenols/kg body weight daily for 14 days. On day 28 of the experiment, blood plasma was collected. One-way ANOVA with post hoc testing revealed a hypoglycemic effect of grape pomace extract, as evidenced by reduced fasting blood glucose and improved postprandial glycemic responses. The extract also ameliorated dyslipidemia, lowering total cholesterol and triglycerides while increasing high-density lipoprotein levels and paraoxonase activity in plasma of diabetic rats. Antioxidant defenses were enhanced, as indicated by elevated superoxide dismutase, catalase, and glutathione peroxidase activities, along with reduced protein carbonyls, TBA-reactive products, and lipofuscin in blood plasma following extract administration. These findings demonstrate the metabolic and antioxidant potential of grape pomace polyphenols, although further investigations are needed to elucidate the underlying molecular mechanisms. Full article

Estrogen deficiency is associated with endothelial dysfunction, vascular inflammation, increased lipoprotein oxidation, accumulation of lipid-rich material, and platelet activation. The absence of estrogen causes physiological, metabolic, and biochemical changes that increase the risk of cardiometabolic disease development caused by a deregulation in metabolic processes such as lipid metabolism and plasma lipoprotein levels. High-density lipoprotein (HDL) has cardioprotective properties related to the quality and the quantity of its components that can be modified by some nutritional factors. Guava (Psidium guajava L.), a widely cultivated fruit in Mexico, is notable for its high polyunsaturated fatty acid and dietary fiber content in its seeds, but its effect on health is understudied. This study aimed to evaluate the effect of guava-seed supplementation on body weight, blood pressure, lipid profile, HDL composition, and paraoxonase-1 (PON1) activity in an ovariectomized rat model (OVX). Four groups with six adult female Wistar rats each were classified as a SHAM group: rats with simulated ovariectomy; OVX group: rats with ovariectomy; OVX + GS group: ovariectomized rats supplemented with 6 g of guava seeds; OVX + DGS group: ovariectomized rats supplemented with 6 g of defatted guava seeds. Biochemical parameters, size, and lipid concentration of HDL subclasses, apolipoproteins, and PON1 activity were determined. A decrease in body weight gain, systolic blood pressure, mean arterial pressure, and triglycerides in plasma was observed at the end of the experiment in the supplemented groups. The supplementation of 6 g of guava seeds for 30 days decreased biochemical parameters in ovariectomized rats; these results could be attributed to the seed composition, suggesting a protective effect against the risk of developing diseases in menopausal states. Full article

Atherosclerotic cardiovascular disease treatment is being reevaluated, since a residual cardiovascular risk (RCR) persists even in patients who achieve optimal LDL-C values. Underlying causes are metabolic dysfunction, lipoprotein(a), inflammation, and triglyceride-rich lipoproteins and their remnants. Dietary treatment options like time-restricted eating (TRE) are becoming more widely acknowledged for their potential advantages in metabolic health and weight control, as a treatment of atherosclerosis expanding beyond LDL-C medication. Beyond weight loss, TRE (which restricts meals to a window of 6 to 8 h) appears as the most accessible treatment, and has been shown to improve blood pressure, lipid profiles, and glucose regulation through mechanisms like metabolic switching and circadian synchronization. We hypothesize, and will present our arguments, that a key mechanism underlying the cardiovascular and weight-related benefits of TRE is its impact on the circadian regulation of angiopoietin-like protein 4 (ANGPTL4) activity within adipose tissue. Additionally, lipolysis is accelerated by ANGPTL4 activation. TRE, via its actions on ANGPTL4, therefore not only inhibits adipose fatty acid uptake but stimulates their release as well. Additionally, TRE may increase intravascular very low-density lipoprotein (VLDL) catabolism by muscle due to the reduced exposure of lipoprotein lipase (LPL) to competing chylomicrons, known to slow the rate of VLDL catabolism. During the prolonged fasting, VLDL residence time is thus shortened, limiting the exposure to endothelium and hepatic lipases and thus reducing the amount of atherogenic remnant particles. Larger, longer-term randomized controlled studies in a variety of groups are required to further clarify TRE’s function in RCR prevention and therapy. As knowledge of triglyceride lipoprotein (TRL) metabolism expands, a comprehensive strategy for the management of RCR emerges, and a broader spectrum of LPL regulator-based therapeutics is created. Consequently, it is advisable to prioritize further research into the influence of TRE on LPL modulation via ANGPTL4 and ANGPTL8, which provides a natural, accessible, and low-cost alternative. Full article

Remnant cholesterol, contained within triglyceride-rich lipoproteins such as VLDL and IDL, has emerged as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in both the general population and individuals with diabetes. Unlike LDL cholesterol, remnant cholesterol has not traditionally been a therapeutic target, despite growing evidence of its role in the pathophysiology of atherosclerosis. These particles exhibit high atherogenic and pro-inflammatory potential, and their metabolism is altered in states of insulin resistance and hepatic dysfunction, both common in diabetes. Epidemiological studies have shown its association with ischemic heart disease, peripheral artery disease, progression of nephropathy, and cardiovascular events in type 2 diabetes. In individuals with type 1 diabetes (T1D), the evidence is more recent but relevant: elevated levels of remnant cholesterol have been linked to persistent hyperglycemia, diabetic nephropathy, diabetic foot, subclinical myocardial dysfunction, and carotid atherosclerosis, even when LDL-C levels are within target range. Moreover, lifestyle factors such as physical activity and a healthy diet are associated with lower levels of remnant cholesterol, suggesting opportunities for non-pharmacological interventions. Despite this, treatments targeting remnant cholesterol have shown limited efficacy in reducing clinical events, and individuals with T1D remain underrepresented in clinical trials. Overall, this review highlights the need to incorporate remnant cholesterol into the assessment of residual cardiovascular risk and into personalized therapeutic strategies, especially for vulnerable populations such as those with T1D. Full article

Background/Objectives: Hypertriglyceridemia (HTG) is a common multifactorial metabolic disorder often with genetic predisposition. Multiple lines of evidence support a causal role of triglyceride-rich lipoproteins (TRLs) in atherosclerotic cardiovascular disease (ASCVD), with severe HTG leading to pancreatitis and hepatic steatosis. This review covers TRL metabolism, causes and consequences of HTG, current management, and emerging TRL-targeted therapies. Methods: A narrative review was conducted. Results: Pharmacologic therapy with fibrates and omega-3 fatty acids remains the standard treatment for HTG but its efficacy in preventing pancreatitis and ASCVD is limited. Genetic studies have identified apolipoprotein C-III (ApoC-III) and angiopoietin-like 3 (ANGPTL3), both inhibitors of lipoprotein lipase, as potential therapeutic targets for reducing TG levels and ASCVD risk. Monoclonal antibodies and RNA-based therapies have enabled the development of inhibitors of ApoC-III and ANGPTL3, with promising results in phase 2 and small phase 3 trials. Angiopoietin-like 4 inhibitors and Fibroblast growth factor 21 analogs are in early-stage clinical development. Conclusions: Current pharmacologic therapies exhibit notable limitations in effectively managing severe HTG and in reducing the risk of ASCVD. Emerging therapies targeting TRLs metabolism showed favourable results in initial clinical trials. 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: Hyperlipidemia is a major risk factor for cardiovascular disease and atherosclerosis. Polyphenols found in polyphenol-rich extra virgin olive oil (EVOO) have been shown to possess strong antioxidant, anti-inflammatory, and cardioprotective properties. The present study aimed to assess the effects of two types of EVOO with different polyphenol content and dosages on the lipid profile of hyperlipidemic patients. Methods: In this single-blind, randomized clinical trial, 50 hyperlipidemic patients were randomized to receive either a higher-dose, lower-phenolic EVOO (414 mg/kg phenols, 20 g/day) or a lower-dose, higher-phenolic EVOO (1021 mg/kg phenols, 8 g/day), for a period of 4 weeks. These doses were selected to ensure equivalent daily polyphenol intake in both groups (~8.3 mg of total phenols/day), based on chemical analysis performed using NMR spectroscopy. The volumes used (8–20 g/day) reflect typical daily EVOO intake and were well tolerated by participants. A group of 20 healthy individuals, separated into two groups, also received the two types of EVOO, respectively, for the same duration. Primary endpoints included blood levels of total blood cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, lipoprotein-a (Lpa), and apolipoproteins A1 and B. Measurements were performed at baseline and at the end of the 4-week intervention. Linear mixed models were performed for the data analysis. Results: The higher-phenolic, lower-dose EVOO group showed a more favorable change in total blood cholesterol (p = 0.045) compared to the lower-phenolic, higher-dose group. EVOO intake was associated with a significant increase in HDL (p < 0.001) and reduction in Lp(a) (p = 0.040) among hyperlipidemic patients in comparison to healthy individuals. Conclusions: EVOO consumption significantly improved the lipid profile of hyperlipidemic patients. Higher-phenolic EVOO at lower dosages appears to be more effective in improving the lipid profile than lower-phenolic EVOO in higher dosages. Full article

Background/Objectives: Nutraceuticals containing milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are purported to abate age-related metabolic dysfunction due to their richness in milk sphingolipids. As such, nutraceuticals offer a compelling strategy to improve metabolic health through dietary means, especially for elderly persons who are unable to adhere to common therapeutic interventions. To address this, we examined the effects of supplementing aged sedentary rats with an MFGM/EV-rich concentrate. Methods/Results: In a 25-week study, 89-week-old male rats received either a milk sphingolipid-rich MFGM/EV concentrate or a control supplement. Analysis of metabolic health using a battery of tests, including MS^ALL lipidomics of plasma, liver, and other peripheral tissues, revealed that MFGM/EV supplementation promotes accretion of unique sphingolipid signatures, ameliorates ceramide biomarkers predictive of cardiovascular death, and has a general lipid-lowering effect. At the functional level, we find that these health-promoting effects are linked to increased lipoprotein particle turnover, showcased by reduced levels of triglyceride-rich particles, as well as a metabolically healthier liver, assessed using whole-body lipidomic flux analysis. Conclusions: Altogether, our work unveils that MFGM/EV-containing food holds a potential for ameliorating age-related metabolic dysfunction in elderly individuals. Full article

Metabolic syndrome (MetS) is a complex cluster of interrelated metabolic disorders that significantly elevate the risk of cardiovascular disease, making it a pressing public health concern worldwide. Among the key features of MetS, dyslipidemia—characterized by altered levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)—plays a crucial role in the disorder’s progression. This review aims to elucidate the intricate interplay between HDL-C and TG within the context of lipid metabolism and cardiovascular health, while also addressing the detrimental impact of various cardiovascular risk factors and associated comorbidities. The dynamics of HDL-C and TG are explored, highlighting their reciprocal relationship and respective contributions to the pathophysiology of MetS. Elevated levels of TGs are consistently associated with reduced concentrations of HDL-C, resulting in a lipid profile that promotes the development of vascular disease. Specifically, as TG levels rise, the protective cardiovascular effects of HDL-C are diminished, leading to the increased accumulation of pro-atherogenic TG-rich lipoproteins and low-density lipoprotein particles within the vascular wall, contributing to the progression of atheromas, which can ultimately result in significant ischemic cardiovascular events. Ultimately, this paper underscores the significance of HDL and TG as essential targets for therapeutic intervention, emphasizing their potential in effectively managing MetS and reducing cardiovascular risk. Full article

Background: Cannabidiol (CBD) exerts diverse metabolic effects, yet its influence on intestinal lipid metabolism remains unclear. Methods: In this study, we investigated whether short-term (one-week) CBD treatment affects lipid absorption and transport through the lymphatic system using a validated lymph fistula model. Results: CBD treatment significantly enhanced the transport of radiolabeled triglycerides through the lymphatic system. This effect appeared specific, as CBD did not substantially alter cholesterol output in the lymph. Chemical assays indicated that CBD treatment did not significantly alter total triglycerides, cholesterol, phospholipids, or non-esterified fatty acid levels in the lymph. However, it significantly enhanced the lymphatic output of apolipoprotein A4 (ApoA4) and apolipoprotein A1 (ApoA1). Additionally, gene expression analysis revealed a downregulation of vascular endothelial growth factor receptor 1 (Flt1) in the small intestine, leading to increased lymphatic lacteal permeability and altered lipid transport dynamics. Conclusions: These findings indicate that short-term CBD treatment modulates lymphatic lipid composition and apolipoprotein secretion by regulating lymphatic lacteal function, thereby influencing lipid transport and metabolism. This study provides novel insights into CBD’s role in facilitating TG-rich lipoprotein transport via the lymphatic system, highlighting its potential therapeutic applications in lipid-related disorders. Full article

Hypertriglyceridemia (HTG) is associated with a residual risk of atherosclerotic cardiovascular disease. Extremely elevated triglyceride (TG) concentrations, particularly due to familial chylomicronemia syndrome (FCS), pose a risk for acute pancreatitis. Standard therapies with statins, fibrates, omega-3 fatty acids, and niacin may be insufficient to reduce elevated TG levels and improve clinical outcomes in patients with HTG. Novel antisense oligonucleotides and small interfering ribonucleic acids target the key modulators of TG-rich lipoprotein catabolism. Among apolipoprotein C-III (apoC-III) inhibitors, olezarsen and plozasiran appear to be safer alternatives for volanesorsen regarding the risk of drug-induced thrombocytopenia in patients with FCS or severe HTG. After the failure of vupanorsen, a new angiopoietin-like protein 3 (ANGPTL3) inhibitor, zodasiran, demonstrated the potential to decrease TG levels in patients with moderate HTG. Meanwhile, the fibroblast growth factor 21 (FGF21) analog, pegozafermin, became another candidate for the treatment of severe HTG. This comprehensive review outlines pharmacological targets in TG-rich lipoprotein metabolism, discusses international guidelines, and summarizes the latest evidence from clinical trials to provide insight into the current and emerging treatment options for primary HTG. Full article

Metabolic syndrome is a cluster of risk factors, including abdominal obesity, insulin resistance, hypertension, dyslipidemia (intended as an increase in triglyceride levels and a reduction in HDL cholesterol levels), and elevated fasting glucose, that increase the risk of cardiovascular disease and type 2 diabetes. With the rising prevalence of metabolic syndrome, effective dietary interventions are essential in reducing these health risks. The Mediterranean diet, rich in fruits, vegetables, whole grains, legumes, nuts, and olive oil and moderate in fish and poultry, has shown promise in addressing metabolic syndrome and its associated components. This diet’s anti-inflammatory and antioxidant properties, primarily due to its unsaturated fats, polyphenols, and fiber, have improved blood pressure, lipid levels, and insulin sensitivity. Adherence to the Mediterranean diet has been linked to reductions in central obesity and insulin resistance, both key elements in managing metabolic syndrome. Regarding lipid management, the Mediterranean diet lowers triglyceride levels and low-density lipoprotein (LDL) cholesterol while raising high-density lipoprotein (HDL) cholesterol, enhancing lipid profiles. It also helps regulate blood glucose levels, reducing the likelihood of developing type 2 diabetes. Additionally, the diet promotes weight loss and improves body composition, particularly by decreasing visceral fat, a primary driver of metabolic syndrome according to IDF classification. The Mediterranean diet offers a holistic approach to managing metabolic syndrome and reducing the risk of related chronic diseases. Its positive impact on metabolic health, combined with lifestyle changes like increased physical activity, provides a sustainable method for addressing the global burden of this syndrome. This review aimed to summarize the positive effects of the Mediterranean diet on the component of the metabolic syndrome with subsequent positive effects on cardiometabolic risk profile. Full article

Background: Dyslipidemia, a leading risk factor for cardiovascular diseases (CVDs), significantly contributes to global morbidity and mortality. Rice bran, rich in bioactive compounds such as γ-oryzanol and tocotrienols, has demonstrated promising lipid-modulating effects. Objective: This meta-analysis aimed to evaluate the effects of rice bran on lipid profiles, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and identify factors influencing its efficacy across different populations and intervention conditions. Methods: A systematic search of PubMed, Web of Science, and Scopus was conducted to identify randomized controlled trials (RCTs) published up to November 2024. Effect sizes were calculated as mean differences with 95% confidence intervals (CIs). Subgroup analyses were performed based on intervention form, dosage, duration, region, and participant characteristics. Heterogeneity was estimated by the I² statistic, and sensitivity analyses were conducted to assess the robustness of the findings. Results: Eleven RCTs involving 572 participants met the inclusion criteria. Pooled results showed that rice bran consumption significantly reduced TG (−15.13 mg/dL; 95% CI: −29.56, −0.71), TC (−11.80 mg/dL; 95% CI: −19.35, −4.25), and LDL-C (−15.11 mg/dL; 95% CI: −24.56, −5.66) with moderate heterogeneity (I² = 38.1–63.0%). No significant changes were observed for HDL-C. Subgroup analyses showed that rice bran oil had greater effects on TC and LDL-C than whole rice bran. High-dose interventions (≥30 g/mL) and longer durations (>4 weeks) yielded stronger effects. Asian populations demonstrated greater reductions compared to Western populations. Conclusion: Rice bran, especially in the form of rice bran oil, significantly improves lipid profiles, supporting its role as a functional food for CVD prevention. Future research should focus on long-term studies with diverse populations to confirm its efficacy and explore underlying mechanisms. Full article