Lipids最新文献

Plant sterols are known for their hypocholesterolemic action, and the molecular mechanisms behind this within the gut have been extensively discussed and demonstrated to the point that there is a degree of consensus. However, recent studies show that these molecules exert an additional umbrella of therapeutic effects in other tissues, which are related to immune function, lipid metabolism, and glucose metabolism. A strong hypothesis to explain these effects is the structural relationship between plant sterols and the ligands of a group of nuclear receptors. This review delves into the molecular aspects of therapeutic effects related with lipid and energy metabolism that have been observed and demonstrated for plant sterols, and turns the perspective to explore the involvement of nuclear receptors as part of these mechanisms.

Inflammation and oxidative stress are the key factors in the pathogenesis of both metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerosis. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, improves hepatic inflammation and fibrosis in patients with MASH. However, it also reduces HDL cholesterol, suggesting that OCA may increase cardiovascular disease (CVD) risk in patients with MASH. We assessed HDL cholesterol efflux function, antioxidant (paraoxonase and ceruloplasmin activity), pro-inflammatory index, and particle sizes in a small group of patients with and without diabetes (n = 10/group) at baseline and after 18 months of OCA treatment. Patients on lipid-lowering medications (statins, fibrates) were excluded. At baseline, ferritin levels were higher in patients with MASH without diabetes (336.5 [157.0, 451.0] vs. 83 [36.0, 151.0] ng/mL, p < 0.005). Markers of HDL functions were similar in both groups. OCA therapy significantly improved liver histology and liver enzymes but increased alkaline phosphatase levels in nondiabetic patients with MASH (p < 0.05). However, it did not have any significant effect on cholesterol efflux and the antioxidant paraoxonase functions. In nondiabetics, ceruloplasmin (CP) antioxidant activity decreased (p < 0.005) and the pro-inflammatory index of HDL increased (p < 0.005) due to OCA therapy. In contrast, in diabetics, OCA increased levels of pre-β-HDL—the HDL particles enhanced protective capacity (p = 0.005) with no alteration in HDL functionality. In all patients, serum glucose levels were negatively correlated with OCA-induced change in pro-inflammatory function in HDL (p < 0.001), which was primarily due to diabetes (p = 0.05). These preliminary results suggest a distinct effect of OCA therapy on diabetic and nondiabetic patients with MASH and warrant a future large-scale study.

Recent studies have demonstrated that ultraviolet B (UVB) irradiation impacts both skin and hepatic functions. In this study, we investigated the effects of UVB irradiation on cholesterol metabolism in the liver. Hairless mice were exposed to UVB (1.6 J/cm²) irradiation. Dorsal skin and liver samples were collected 24 h after exposure. Total RNA was extracted from the skin and liver tissues, and used for DNA microarray analysis and real-time polymerase chain reaction (PCR). Hepatic mRNA expression of Cyp7a1 revealed a 4.4-fold decrease in the UVB (+) group compared to that in the UVB (−) group. No differences were observed in the expression of the other genes related to cholesterol metabolism. Additionally, the level of hepatic total cholesterol in the UVB (+) group was significantly higher than in the UVB (−) group. These findings suggest that acute UVB irradiation increases total cholesterol levels and decreases Cyp7a1 expression in the liver.

Omega-3-acid ethyl acetate 90 capsules (containing 465 mg of eicosapentaenoic acid and 375 mg docosahexaenoic acid) is composed of highly purified omega-3 polyunsaturated fatty acid (PUFA) ethyl esters, whose lipid-lowering effect for severe hypertriglyceridemia (HTG) treatment is unclear. This study aimed to evaluate the efficacy and safety of omega-3-acid ethyl acetate 90 capsules in patients with severe HTG. In this randomized, double-blind, placebo-controlled, multicenter study, 239 patients with severe HTG were enrolled and randomized (1:1) into omega-3 group (N = 122) and placebo group (N = 117) to receive 12-week corresponding treatments. Lipid-related indexes were obtained at treatment initiation (W0), 4 weeks (W4), W8, and W12 after treatment. Adverse events and adverse drug reactions were recorded. Triacylglycerols (TAG), total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), and apolipoprotein C-III (Apo C-III) at W4, W8, and W12 were decreased in the omega-3 group versus the placebo group (all p < 0.05). Moreover, the percentage changes of TAG, TC, non-HDL-C, and VLDL-C from W0 to W4, W8, and W12, and the percentage change of Apo C-III from W0 to W4 and W8, were more obvious in the omega-3 group compared with the placebo group (all p < 0.05). However, no difference was observed in the percentage changes of HDL-C, low-density lipoprotein cholesterol (LDL-C), and LDL-C/HDL-C ratio during follow-up between groups (all p > 0.05). Additionally, there was no discrepancy in adverse events and adverse drug reactions between groups (all p > 0.05). Omega-3-acid ethyl acetate 90 capsules exhibit satisfied lipid-lowering effect with tolerable safety profile in patients with severe HTG.

The objective of this study was to determine the effects of different lipid sources, with or without a probiotic, on the gastrointestinal tract, immune system and blood parameters of Ross 308 male chickens. In this study, 360 one-day-old chickens were randomly allotted to six treatments with six replicates. Experimental diets were: (1) control (CTL); (2) a diet containing 30 g/kg lipid from tallow (CTL+TLW); (3) a diet containing 30 g/kg lipid from soybean oil (CTL+SO); (4) the basal diet plus a probiotic (CTL+PRO), (5) a diet containing 30 g/kg tallow plus probiotic (TLW+PRO); and (6) a diet containing 30 g/kg soybean oil plus probiotic (SO+PRO). The percentage of liver and jejunum in the treatments that used tallow alone or tallow with probiotics had a significant increase as compared to the control. The villus height and crypt depth of the ileum and villus height/crypt depth in the treatments that used soybean oil and probiotic alone had a significant increase compared to the control. The weight of the spleen, bursa of Fabricius, and thymus in the treatments that used probiotics had a significant increase compared to the control. The amount of alkaline phosphatase and alanine aminotransferase as well as triacylglycerol in the treatment containing probiotic and its mixture with soybean oil had the least significant difference with the control. The results showed that the use of soybean oil, probiotics, and their mixture can improve intestinal morphology, strengthen the immune system, and reduce liver enzymes in chickens.

The study aimed to assess the effect of high-intensity statin therapy on testicular and adrenal steroids and vitamin D levels in type 2 diabetic men. A prospective study, conducted between March 2021 and July 2022, including 60 men with type 2 diabetes, aged 40–65 years, statin-free, and in whom treatment with high-intensity statin was indicated. The patients had two visits, before and 6 months after a daily intake of 40 mg of atorvastatin. During each visit, they underwent a clinical examination, and a fasting blood sample was collected for biological and hormonal measurements. There was a significant increase in the prevalence of decreased libido (from 22% to 47%, p = 0.001) and a significant decrease in the frequency of sexual intercourse (from 4 [1–8] to 3 [0–4] per month, p = 0.005). The median ADAM's score significantly increased (from 4 [2–7] to 6 [3–8], p = 0.000). Twenty-two percent of the patients developed gynecomastia. The median total, bioavailable and free testosterone significantly decreased from 15.1 (11.4–17.4), 6.3 (5.0–7.8), and 0.27 (0.22–0.33) nmol/L to 12.7 (10.7–15.9), 5.7 (4.4–7.0), and 0.24 (0.19–0.30) nmol/L, respectively, with no change in FSH and LH levels. Three patients (5%) developed hypogonadism (testosterone <8 nmol/L). There was a significant decrease in DHEAS from 4.5 (2.8–6.1) to 3.8 μmol/L (2.6–5.6) and no change in cortisol and vitamin D levels. High-intensity statin therapy decreased androgen levels in type 2 diabetic men with significant clinical impact.

Behçet's disease (BD) is a systemic disease with unknown etiopathogenesis and varying disease presentations. Fatty acids (FA) are essential biological compounds that are involved in complex metabolic pathways. They may contribute to inflammation and endothelial dysfunction by participating in many signaling pathways. Increased FAs levels are associated with an increased risk for various diseases. This study aimed to determine the relationship between FA, BD, and thrombotic complications. A total of 97 patients were recruited from the rheumatology department of a single center as a case–control study. The participants were divided into three groups: 36 patients with BD with thrombosis (Group 1), 24 patients with BD without thrombosis (Group 2), and 37 age- and sex-matched controls (Group 3). The analysis of 37 different FA with carbon numbers in the range of (4:0) and (24:1) in the samples were analyzed and compared between groups. Myristic acid (MA), methyl eicosatrienoate, and stearic acid (STA) levels were found to be significantly higher in BD with thrombosis than in BD without thrombosis, and palmitic acid (PA) levels were significantly higher in BD with thrombosis than in healthy individuals. MA was found to be a significant marker for differentiating between thrombotic BD. PA and STA are important markers for detecting thrombotic BD. In BD, lipotoxicity created by FA, such as PA, STA, and MA, plays a role as an inducer of inflammation and thrombosis through various mechanisms.

The elderly population is at a higher risk of cardiovascular complications, and dyslipidemia plays a significant role as a contributing factor. Chronic kidney disease (CKD) patients are prone to lipid abnormalities, further increasing the risk of cardiovascular complications. We aimed to investigate the lipid profile characteristics of the middle-aged and elderly population, particularly CKD patients. We conducted a cross-sectional study using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). It was examined how lipid profiles are affected by age within the general population, and how BMI and lipid characteristics are affected by CKD subtype. Among 8746 participants, we observed a decreasing trend in LnTAG (natural logarithm of Triacylglycerol) and total Cholesterol (CHR) levels with increasing age, while high-density lipoprotein cholesterol (HDL-C) levels increased with age. In the CKD and non-CKD subgroups created through propensity score matching based on age, sex, and race, CKD individuals exhibited significantly higher average LnTAG levels across all age groups compared to the non-CKD group. Multivariable linear regression analysis, controlling for confounding variables, revealed a negative correlation between LnTAG and estimated glomerular filtration rate (eGFR) (r = −0.002, p < 0.001). HDL-C showed a positive correlation with eGFR (r = 0.001, p < 0.001). [Correction added on 1 July 2024, after first online publication: The value of r in the preceding sentence has been updated to r = 0.001.] That is, in the middle-aged and elderly population, age demonstrated a negative correlation with total CHR and TAG levels, while exhibiting a positive correlation with HDL-C levels. CKD patients exhibited relatively higher TAG levels, which were positively associated with CKD progression.

The monocyte-to-high-density lipoprotein cholesterol ratio (MHR) is a novel marker that can help estimate the degree of atherosclerosis by considering inflammation and lipid abnormalities. This study aimed to assess the association between the MHR and prevalent heart failure (HF) and to explore the value of the MHR in detecting prevalent HF in the general US population. Our study included 25,374 participants from the National Health and Nutrition Examination Survey (1999–2018). Among the participants, 749 (2.95%) reported a history of HF, and the HF group had a significantly higher MHR than the non-HF group. Adjusted analyses revealed that each standard deviation increase in the MHR was associated with a 27.8% increase in the risk of HF. The association between the MHR and prevalent HF was linear across the entire MHR range. Adding the MHR to conventional cardiovascular risk factors significantly improved the area under the curve (0.875; p < 0.001), continuous net reclassification index (0.187; p < 0.001), and integrated discrimination index (0.004; p < 0.001). Our study suggests a potential association between the MHR and HF risk, and the findings enhance HF risk stratification and provide novel insights into the interplay between the coronary atherosclerotic burden and HF in clinical settings.

The ideal approach to the secondary dyslipidemia goal of lowering triglycerides (TG) is not well established. The available ω-3 fatty acid products differ from each other in composition and content. The purpose of the present study was to investigate the effect of a highly purified eicosapentaenoic acid (EPA) formulation on cardiometabolic biomarkers in high cardiovascular (CV) risk patients. The study included 226 subjects with high TG and ≥1 of the following CV risk factors: arterial hypertension, diabetes mellitus, ultrasound-documented atheromatosis, peripheral artery disease, previous myocardial infarction, or ischemic stroke. Participants received 2 g EPA twice daily for 3 months, along with typical nutritional counseling. Cardiometabolic hematological parameters (TG, low-density lipoprotein [LDL], high-density lipoprotein [HDL], non-HDL, total cholesterol [TChol], apolipoprotein A₁ [Apo A₁], apolipoprotein B [Apo B], glucose, glycated hemoglobin [HbA₁c], and C-reactive protein [CRP]) were measured at baseline and at 3 months. The mean patients' age was 61.1 ± 1.4 years and the mean baseline TG was 2.97 ± 0.15 mmol/L. Apart from Apo A₁, all other biomarkers significantly (p < 0.05) improved at 3 months, regardless of sex (except Apo B) and age: TG 1.75 ± 0.09 versus 2.97 ± 0.15 mmol/L, LDL 2.46 ± 0.08 versus 3.05 ± 0.13 mmol/L, HDL 1.22 ± 0.03 versus 1.11 ± 0.03 mmol/L, non-HDL 3.29 ± 0.10 versus 4.14 ± 0.16 mmol/L, TChol 4.55 ± 0.10 versus 5.15 ± 0.13 mmol/L, Apo A₁ 26.8 ± 9.3 versus 22.5 ± 8.6 μmol/L, Apo B 1.25 ± 0.23 versus 1.29 ± 0.23 μmol/L, glucose 5.66 ± 0.11 versus 5.99 ± 0.17 mmol/L, HbA₁c 5.83 ± 0.1 versus 5.97 ± 0.1% and CRP 1.92 ± 0.2 versus 5.26 ± 2.8 mg/L. In conclusion, adding highly purified EPA product (4 g daily) on nutritional counseling leads to a significant TG reduction. In addition, this treatment appears to have pleiotropic beneficial cardiometabolic actions.