Lipids最新文献

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.

Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue. Lipid metabolism disorders may contribute to osteoporosis in postmenopausal women. Phytosterols and oxysterols (OC) are involved in lipid metabolism. However, their roles in bone metabolism and in the development of osteoporosis remain unclear. This study used ovariectomized (OVX) rats, commonly used to study osteoporosis, to analyze the levels of sterols, including phytosterols, cholesterol, and oxysterols in the humerus, femur, femoral bone marrow, blood, and liver. Sterol levels were measured through gas chromatography. We observed that campesterol and cholesterol exhibited similar patterns of change in the blood, liver, and bone marrow. Conversely, cholesterol and campesterol levels in the femur did not change significantly, while bone marrow cholesterol levels decreased. The similar changes in campesterol and cholesterol levels suggest that these sterols are derived from the blood and taken up by the bone marrow. Significant increases in 4β-hydroxycholesterol were found in the humerus, plasma, and liver of OVX rats. The ratio of 4β-hydroxycholesterol to cholesterol in the bone marrow was significantly increased in OVX rats. These findings suggest that 4β-hydroxycholesterol is associated with OVX-induced osteoporosis and contributes to the decline in bone density.

Cashew nut oil adds value to the production chain of this Brazilian oilseed. It is a good source of monounsaturated and polyunsaturated fatty acids and bioactive compounds, such as phenolics. This study investigated the effects of cashew nut oil on the metabolism of animals subjected to a high-fat diet. C57BL/6J mice were fed a high-fat diet (12 weeks), then switched to diets containing cashew nut oil, soybean oil, or lard (12 weeks). Diets were characterized for their fatty acid profile. General parameters, metabolic markers, oxidative stress, gene expression, and liver steatosis were evaluated. Oleic acid was predominant in the cashew nut oil-added diet, linoleic acid in the soybean oil-added diet, and palmitic acid in the lard-added diet. Cashew nut oil reduced blood glucose, triglycerides, uric acid, and liver steatosis, and increased SOD expression and activity and catalase activity. Soybean oil reduced blood glucose, total cholesterol, LDL cholesterol, triglycerides, and liver steatosis. Both vegetable oils, rich in unsaturated fatty acids, demonstrated more benefits than animal fat. Cashew nut oil effects may be mediated by the reduction of hepatic fat accumulation and oxidative stress, leading to lower triglyceride levels, improved insulin signaling, and decreased uric acid, probably due to its fatty acid composition, rich in oleic acid. Phenolic compounds may enhance its antioxidant capacity. The quality of fatty acids and the bioactive compounds is a determinant of the metabolic effect of oils. Cashew nut oil may improve lipid metabolism, reduce liver steatosis, and enhance antioxidant effects.