Lipids最新文献

Dysregulated lipid metabolism fuels cancer progression through enhanced lipogenesis, cholesterol synthesis, and fatty acid oxidation. Herbal bioactives provide multi-targeted molecular interventions capable of restoring lipid homeostasis while minimizing toxicity. Guggulsterone (GS), a plant-derived steroidal compound from Commiphora mukul, exemplifies this paradigm by modulating key regulators such as ATP citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), farnesoid X receptor (FXR), and AMP-activated protein kinase (AMPK). Through these actions, it suppresses oncogenic lipid signaling, reprograms the tumor microenvironment, and enhances apoptotic sensitivity. This article outlines the molecular underpinnings of GS's lipid-lowering and antitumor effects, emphasizing its potential as a pharmacological scaffold for metabolic reprogramming in cancer.

Elevated plasma lipoprotein(a) (Lp(a)) (> 125 nmol/L) is highly prevalent and a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) that may contribute significantly to plasma levels of low-density lipoprotein-cholesterol (LDL-C). This study aimed to describe clinical characteristics across Lp(a) levels and to estimate the proportion of individuals with normal, moderately elevated, or elevated LDL-C earlier in life according to levels of Lp(a), to assess whether LDL-C levels are a reliable marker for an underlying elevated Lp(a) level. In this retrospective study, detailed information on clinical characteristics was collected through medical records, while biochemical data was retrieved from the North Denmark Region Clinical Laboratory System (LABKA) I and II between January 2021 and August 2024. A total of 1346 individuals were included of whom 28.5% had elevated Lp(a) levels ≥ 125 nmol/L. A history of ASCVD was found in 57.7% of patients with Lp(a) levels ≥ 400 nmol/L compared to 21.1% of patients with Lp(a) levels < 100 nmol/L and the median age of onset of ASCVD was 51 years and 56 years, respectively. Furthermore, in individuals with Lp(a) levels ≥ 300 nmol/L, we found that 7.6% had LDL-C < 3.0 mmol/L and 9.1% had LDL-C between 3.0 and 3.5 mmol/L when measured for the first time, respectively. This study highlights distinct clinical characteristics across Lp(a) levels. With increasing Lp(a) levels, the prevalence of ASCVD increased, while the age at onset of ASCVD decreased. Furthermore, we found that LDL-C within the normal range cannot be used to rule out highly elevated Lp(a) levels.

The non-high-density lipoprotein cholesterol (non-HDL-c) to high-density lipoprotein cholesterol (HDL-c) ratio (NHHR) is an emerging and valuable biomarker for cardiovascular disease risk. Nevertheless, robust evidence regarding its relationship with both the prevalence and severity of albuminuria remains incompletely elucidated. This cross-sectional study analyzed data from the 1999 to 2018 US National Health and Nutrition Examination Survey to investigate the association between NHHR and albuminuria, assessed via the urinary albumin-to-creatinine ratio (uACR). Multivariate logistic and linear regression models, restricted cubic spline analysis, subgroup analyses and receiver-operating characteristic curve analysis were employed. Among the 14,376 participants included, the prevalence of microalbuminuria and macroalbuminuria was 6.83% and 1.06%, respectively. The adjusted odds ratios (95% confidence intervals) for each one-unit increase in NHHR were 1.09 (1.04-1.15) for any albuminuria, 1.06 (1.01-1.12) for microalbuminuria, and 1.23 (1.11-1.37) for macroalbuminuria. NHHR was positively correlated with uACR (β = 4.08, 95% confidence interval 1.11-7.04). Restricted cubic spline analysis revealed a positive association, which became more pronounced at NHHR levels exceeding 2.77. Subgroup analyses further demonstrated that this association was stronger in individuals with a body mass index ≥ 30 kg/m² or an estimated glomerular filtration rate ≥ 90 mL/min/1.73 m². Receiver-operating characteristic curve analysis confirmed that NHHR possessed superior discriminative power for albuminuria compared to conventional lipid parameters of total cholesterol, HDL-c, non-HDL-c, triglycerides, and apolipoprotein B. We concluded that elevated NHHR is positively and independently associated with an increased risk and severity of albuminuria, highlighting its clinical relevance as a potential biomarker, particularly among individuals with obesity and preserved renal function.

7-Ketocholesterol (7-KC), a cytotoxic oxysterol, contributes to atherosclerosis, neurodegeneration, and metabolic disorders by promoting oxidative stress, inflammation, and dysfunction of organelles including mitochondria, peroxisomes, lysosomes, and the endoplasmic reticulum, ultimately leading to cell death. Nutritional biomedicine offers potential strategies to counteract these effects using antioxidant nutrients and probiotics. In this study, genes associated with 7-KC toxicity were retrieved from GeneCards, and targets of quercetin, luteolin, butyrate, Docosahexaenoic Acid (DHA), and vitamin E were predicted using SwissTargetPrediction. Overlapping targets were identified via an interactive Venn tool and analyzed through STRING protein-protein interaction networks, CytoHubba hub ranking, and Gene Ontology (GO)/ClueGO pathway enrichment. Twenty shared genes were identified, with Peroxisome Proliferator-Activated Receptor Gamma (PPARG), AKT Serine/Threonine Kinase 1 (AKT1), Amyloid Precursor Protein (APP), and Matrix Metalloproteinase-9 (MMP9) as key hubs. Enriched processes included sterol metabolism, cholesterol efflux, inflammatory regulation, and organelle protection, indicating multi-target modulation. These findings support that combinatorial nutrient interventions can restore sterol homeostasis, mitigate oxidative stress, and attenuate 7-KC-induced pathologies.

To examine the disparities in adipose tissue browning between diets rich in lard and soybean oil under low and recommended caloric intake conditions. In this study, sixty 8-week-old male C57BL/6J mice were randomly divided into four groups fed purified diets with 15% and 25% energy provided as lard or soybean oil. After 20 weeks, the mice were dissected and the tissues were collected. Only at the 25% level was there a significant difference in the brown adipose tissue between the two groups of mice fed different oils. The expression of mRNA related to the BAT was tested by qPCR methods. Diversity of microbiota in cecal content was evaluated by the 16S rRNA sequencing. Compared with soybean oil, the BAT weight of the lard group was significantly increased (p < 0.05), and the protein expression of UCP1 in iWAT was significantly higher (p < 0.05). The expression levels of adipose browning, thermogenesis and mitochondria genes were significantly increased in the lard group, and lipogenesis-related genes were significantly decreased (p < 0.05). The proportions of Akkermansia, Romboutsia, Lactobacillus, and Streptococcus were significantly increased in the lard group (p < 0.05). This study suggests that at the dietary fat energy level of 25%, feeding with lard could promote the browning of fat, improve lipid metabolism, and increase the abundance of beneficial bacteria in the gut.

We report hepatic and renal parameters affected by fixed oil from ginger (Zingiber officinale) and black pepper (Piper nigrum) in male Wistar rats. Dyslipidaemia (hyperlipidemia) and diabetes were induced by feeding 35% saturated fat for 30 days, followed by the administration of streptozotocin (28 mg/kg bw). Rats were grouped into: DD (dyslipidaemia with diabetes), DD + M + O [metformin (20 mg/kg bw) + orlistat (10 mg/kg bw)], DD + G-FO [ginger fixed oil (50 mg/kg bw)], DD + P-FO [black pepper fixed oil (50 mg/kg bw)] and control with 60-days feeding. The DD group had significantly elevated lipids (total cholesterol, LDL + VLDL cholesterol, and triglycerides), glycaemic parameters (FBS, insulin, HbA1c, and HOMA-IR), organ function enzyme markers (ALP, CK-MB, CK-NAC, SGOT, and SGPT) compared to control (p < 0.05), whereas experimental groups (DD + G-FO and DD + P-FO) showed a significant decrease compared to DD (p < 0.05). The hepatic levels of caspase-3, cytochrome c, and p53 were increased significantly in DD compared to the control and experimental groups (p < 0.05). Similarly, kidney injury molecule-1 (KIM-1), in both serum and kidney, was significantly increased in DD compared to the control and experimental groups. The hepatic (bilirubin) and renal (urea, uric acid, and creatinine) markers were elevated significantly in DD compared to the control and experimental groups (p < 0.05). Liver and kidney histology indicated that DD enhanced lipid accumulation, resulting in tissue damage compared to the control and experimental groups. Thus, we established that fixed oil from ginger and black pepper sustained hepatic and renal function in metabolic abnormalities like hyperlipidemia and diabetes in the experimental rat model.

Although sphingolipids are key players in lipotoxicity and metabolic diseases, their response to bariatric surgery and their relation to metabolic improvement remain unclear. This pilot study investigated plasma sphingolipid remodeling after Roux-en-Y gastric bypass (RYGB) and its associations with clinical and biochemical markers of postoperative metabolic improvement in women with obesity and type 2 diabetes (T2DM). Plasma samples, anthropometric, body composition, and biochemical data (glucose, HbA1c, insulin, C-peptide, and lipid profile) were collected from 30 participants before and 3 months after surgery. T2DM remission was defined according to ADA 2021 criteria. Plasma sphingolipids were identified using untargeted metabolomics, which involved ultra-performance liquid chromatography coupled with mass spectrometry. Univariate and multivariate analyses were performed using Jamovi (version 2.2.5) and MetaboAnalyst (versions 5.0 and 6.0). RYGB led to reductions in body weight and anthropometric measures, with improved body composition. Patients demonstrated glycemic improvement, with 18 achieving remission of T2DM. The lipid profile also improved, with a decline in total cholesterol driven by reductions in pro-atherogenic fractions. Among 32 plasma sphingolipids identified, 21 changed significantly after surgery. Sphingolipids showed strong-to-robust correlations with the lipid profile, particularly SM(d18:1/20:0) and SM(d18:1/22:0) with total cholesterol and LDL-c after surgery, but moderate and poor correlations with body composition, and glycemic markers, respectively. Plasma sphingolipids underwent significant remodeling after RYGB, with strong associations with plasma cholesterol, particularly with SM(d18:1/20:0) and SM(d18:1/22:0). These findings suggest that specific sphingolipid species may contribute to or reflect plasma lipid adaptations to surgery and warrant further investigation as potential metabolic biomarkers. Trial Registration: This protocol is part of a broader umbrella study registered at www.clinicaltrials.gov under the identifier NCT01251016.

The triglyceride glucose (TyG) index is increasingly recognized as a simple yet reliable surrogate marker of insulin resistance. This study aimed to explore the relationship between the TyG index and liver fat content (LFC) quantified via quantitative computed tomography (QCT) in individuals with type 2 diabetes mellitus (T2DM). This cross-sectional analysis included patients with T2DM who underwent QCT examinations at our institution between January and December 2024. QCT was used to measure tissue components at the mid-L2 vertebral level, including subcutaneous fat area (SFA), visceral fat area (VFA), and LFC. A multiple linear regression model was employed to assess the independent association between the TyG index and LFC. The study enrolled 168 participants, comprising 112 males and 56 females. Subjects in the highest TyG index tertile exhibited a more adverse cardiometabolic risk profile and higher LFC compared to those in the lowest tertile. Correlation analyses indicated that the TyG index was significantly associated with both SFA and LFC. After adjusting for age and gender, multiple linear regression confirmed that the TyG index remained independently and positively associated with LFC (β = 1.73, 95% CI: 0.08-3.38, p = 0.042). Stratified analyses revealed that the positive association between the TyG index and LFC was consistent across all strata, with no significant interactions observed for age, gender, duration of T2DM, and body mass index. Our findings suggest that the TyG index may serve as a reliable, noninvasive surrogate marker for evaluating LFC in individuals with T2DM.

Fatty acid beta-oxidation defects (FAOD) are a subgroup of lipid myopathies with heterogeneous presentations. Clinical presentation may manifest as muscular weakness, cramps, postexercise myalgias, and episodic rhabdomyolysis in children or adults. Our objective was to describe the clinical manifestations, biochemical, anatomopathological, and molecular results in a series of adult patients diagnosed with FAOD during adolescence or adulthood at five centers in Argentina. A total of seven patients with carnitine palmitoyltransferase-2 (CPT II), very-long-chain acyl-CoA dehydrogenase (VLCAD), and long-chain 3-hydroxyacyl-CoA dehydrogenase LCHAD deficiency were reported. The definite diagnosis of metabolic myopathies due to FAOD requires an understanding of clinical, biochemical, neurophysiological, and muscular imaging/biopsy patterns. All patients in this series consulted pediatricians, general practitioners, rheumatologists, and orthopedists for years, underscoring the need to disseminate these presentation patterns across various medical specialties. Early diagnosis and treatment using traditional diets and new pharmacological strategies not only enhance the quality of life, but also improve survival in these patients.

The precise involvement of ACSL1 in metabolic-associated fatty liver disease (MAFLD) pathogenesis remains unclear. To this end, we analyzed the effects of long-chain acyl-CoA synthase (ACSL1) on MAFLD. Analysis of GEO datasets showed that ACSL1 was downregulated in MAFLD. To elucidate its mechanistic role, we generated BRL hepatocyte cell lines with stable ACSL1 knockdown or overexpression. These engineered cells were cultured with a lipid mixture containing 300 μM oleic acid, 150 μM palmitic acid, and 100 μM linoleic acid (OPL) to mimic MAFLD pathophysiology in vitro. Lipidomic profiling identified 195 upregulated and 357 downregulated lipid metabolites in OPL-treated ACSL1-knockdown cells (OPL-shACSL1). Notably, the OPL-shACSL1 group exhibited marked elevations in free fatty acids, including linoleic acid, arachidonic acid (AA), FA20:3, FA22:5, and FA22:2, accompanied by enhanced AA metabolism. Western blotting demonstrated that ACSL1 knockdown significantly upregulated key enzymes in AA metabolic pathways, including ELOVL5, COX1, and LOX5. Consistent with these in vitro findings, mice with high-fat diet-induced MAFLD showed reduced hepatic ACSL1 expression with concurrent elevation of COX1 protein levels. Co-immunoprecipitation assays showed that ACSL1 did not interact with LOX5 or COX1. Our findings demonstrate that ACSL1 knockdown enhances AA metabolism, evidenced by elevated levels of AA-related metabolites and upregulated expression of key enzymes (ELOVL5, COX1, LOX5), and suggest that ACSL1 may represent a potential therapeutic target for MAFLD.