Lipids in Health and Disease最新文献

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with many aspects of disturbed metabolic health. MASLD encompasses a wide spectrum of liver diseases, ranging from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), up to fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Limited noninvasive diagnostic tools are currently available to distinguish the various stages of MASLD and as such liver biopsy remains the gold standard for MASLD diagnostics. We aimed to explore whether the plasma lipidome and its variations can serve as a biomarker for MASLD stages.

Methods: We investigated the plasma lipidome of 7 MASLD-free subjects and 32 individuals with MASLD, of whom 11 had MASH based on biopsy scoring.

Results: Compared with the MASLD-free subjects, individuals with MASLD had higher plasma concentrations of sphingolipids, glycerolipids, and glycerophospholipids. Only plasma concentrations of ceramide-1-phosphate C1P(d45:1) and phosphatidylcholine PC(O-36:3), PC(O-38:3), and PC(36:2) differed significantly between presence of MASH in individuals with MASLD. Of these lipids, the first three have a very low relative plasma abundance, thus only PC(36:2) might serve as a biomarker with higher plasma concentrations in MASLD individuals without MASH compared to those with MASH.

Conclusions: Plasma lipids hold promise as biomarkers of MASLD stages, whereas plasma PC(36:2) concentrations would be able to distinguish individuals with MASH from those with MASLD without MASH.

Background: This study aimed to investigate the associations between noninsulin-dependent insulin resistance indices (NI-IRIs), including the triglyceride-glucose (TyG) index, TyG-BMI, triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C), and metabolic score for insulin resistance (METS-IR), as well as the occurrence of restenosis in patients with lower extremity atherosclerotic occlusive disease after drug-coated balloon (DCB) treatment.

Methods: The primary endpoint was restenosis within one year after the procedure, which was defined as ≥ 50% stenosis of the treated artery segment. The association between NI-IRIs and restenosis was assessed via multivariable logistic regression analysis. Restricted cubic spline (RCS) analysis was performed to quantify nonlinearity. The consistency of these associations was confirmed through subgroup and interaction analyses. Additionally, the additional predictive value of NI-IRIs beyond established risk factors for restenosis was evaluated via receiver operating characteristic (ROC) curves, the net reclassification improvement (NRI), and integrated discrimination improvement (IDI) indices.

Results: Except for the TyG index, the other three NI-IRIs demonstrated nonlinear relationships with the probability of postoperative restenosis. Specifically, TG/HDL-C (inflection point: 1.48, P for nonlinearity: 0.003) exhibited a saturating effect, whereas METS-IR (inflection point: 49.30, P for nonlinearity: 0.017) and TyG-BMI (inflection point: 221.53, P for nonlinearity: 0.039) showed threshold effects. Subgroup analysis revealed that the interactions among the subgroups were not statistically significant. Furthermore, among the four NI-IRIs, the addition of the TG/HDL-C index significantly enhanced the predictive power of the base model for restenosis in ASO patients following DCB angioplasty (AUC values: 0.726 vs. 0.760, P = 0.042). The P values for the NRI and IDI were 0.001 and 0.002, respectively.

Conclusion: TG/HDL-C showed a saturating effect on restenosis within one year after DCB treatment in ASO patients, and METS-IR and TyG-BMI showed threshold effects. The addition of the TG/HDL-C index significantly improved the predictive ability of the base model for restenosis in ASO patients who underwent DCB angioplasty.

Background: The uric acid to high-density lipoprotein cholesterol ratio (UHR) has emerged as a novel metabolic marker and is proven to be associated with diabetes risk. However, there is still a lack of systematic research regarding its role in gender differences and underlying mechanisms. This study aims to assess the association of UHR with diabetes risk in the context of gender differences and to investigate its mediation effects through metabolic and inflammatory pathways.

Methods: This study utilized data from NHANES 2005-2010 and included 6,843 adult participants. Multivariate logistic regression was employed to assess the association between UHR and diabetes risk, and restricted cubic spline (RCS) along with correlation analysis was applied to explore its relationship with metabolic risk factors. Multiple mediation analysis was conducted to evaluate the mediating effects of homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), and C-reactive protein (CRP) on the association between UHR and diabetes risk.

Results: In the overall population, UHR was significantly positively associated with diabetes risk, but gender-stratified analysis revealed a stronger predictive effect in women. In the unadjusted model, every unit increase in UHR was linked to an 18.6% increase in diabetes risk in women (p < 0.001). In the quartile analysis, women in the highest quartile showed an 8.49-fold increased risk of diabetes (OR = 8.494, 95% CI: 5.542-13.019, p < 0.001), whereas no significant association was observed in men (p > 0.05). Mediation analysis revealed that HOMA-IR was the main mediator of the relationship between UHR and diabetes risk, with mediation effects of 64.55%, 118.38%, and 39.09% in the overall population, men, and women, respectively. Additionally, the mediation effect of TG was stronger in men (36.78%) and weaker in women (17.31%). The mediation effect of CRP was relatively minimal across all groups, accounting for 7.62% in men and 2.67% in women.

Conclusion: This study demonstrates that the association between UHR and diabetes risk exhibits gender differences, with higher diabetes risk observed in women, while men show stronger mediation effects in insulin resistance, lipid metabolism, and inflammatory response.

Background/aims: Research has indicated that treatment with rosuvastatin can improve liver pathology in metabolic-associated fatty liver disease (MAFLD) patients and that treatment with Bifidobacterium can improve MAFLD. Therefore, the effects of Bifidobacterium, rosuvastatin, and their combination on related indices in a rat model of diet-induced MAFLD need to be investigated.

Methods: Forty rats were divided into five groups: the normal diet group (N), high-fat diet (HFD) model group (M), HFD + probiotic group (P), HFD + statin group (S), and HFD + probiotic + statin group (P-S). To establish the MAFLD model, the rats in Groups M, P, S, and P-S were fed a HFD for 8 weeks. The treatments included saline in Group N and either Bifidobacterium, rosuvastatin, or their combination in Groups P, S, and P-S by intragastrical gavage. After 4 weeks of intervention, the rats were euthanized, and samples were harvested to analyze gastrointestinal motility and liver function, pathological changes, inflammatory cytokine production, and the expression of proteins in key signaling pathways.

Results: HFD feeding significantly increased the body weight, liver index, and insulin resistance (IR) index of the rats, indicating that the MAFLD model was successfully induced. Bifidobacterium reduced the liver of MAFLD rats, while Bifidobacterium with Rosuvastatin decreased the liver index, IR index, and levels of aspartate aminotransferase and alanine aminotransferase in MAFLD rats. The MAFLD model showed altered expression of proteins in signaling pathways that regulate inflammation, increased production of inflammatory cytokines, an elevated MAFLD activity score (MAS), and pathological changes in the liver. The MAFLD model also showed reduced relative counts of intestinal neurons and enteric glial cells (EGCs), altered secretion of gastrointestinal hormones, and slowed gastrointestinal emptying. Bifidobacterium, rosuvastatin, or their combination inhibited these various changes. HFD feeding changed the rats' gut microbiota, and the tested treatments inhibited these changes. These results suggest that the gastrointestinal motility disorder and abnormal liver function in MAFLD rats may be related to a reduction in Escherichia-Shigella bacteria and an increase in Asticcacaulis bacteria in the gut microbiota and that the improvement in liver function induced by Bifidobacterium plus rosuvastatin may be related to increases in Sphingomonas and Odoribacter bacteria and a decrease in Turicibacter bacteria in the gut microbiota.

Conclusions: The combined use of Bifidobacterium and rosuvastatin could better regulate the gut microbiota of MAFLD model rats, promote gastrointestinal emptying, and improve liver pathology and function than single treatment with Bifidobacterium or rosuvastatin. This provides a better strategy for the treatment of MAFLD.

Background: Cardiovascular-kidney-metabolic (CKM) syndrome is characterized as a systemic disease resulting from the pathophysiological interplay among metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). The Klotho protein may serve as a novel biomarker. However, the utility of serum Klotho levels as an indicator of severity and mortality risk in CKM syndrome remains uncertain.

Methods: This study involved 9,871 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. Serum Klotho levels were measured using an enzyme-linked immunosorbent assay kit. The optimal cutoff value was established through the maximum Youden's index. Multivariable weighted regression models were employed to calculate the odds ratio and hazard ratio, along with the 95% confidence interval, to evaluate the association between serum Klotho levels and the severity of CKM syndrome, as well as all-cause and cardiovascular mortality. Additionally, the receiver operating characteristic curve and restricted cubic spline curves were utilized to assess predictive efficacy and to explore nonlinear relationships.

Results: After adjusting for potential confounding factors, a non-linear relationship was seen between the Klotho protein, and CKM syndrome. In the multivariable, piecewise logistic regression, when the Serum klotho was less than 801, the risk of CKM syndrome decreased with the increase in Serum klotho (OR = 0.82, 95%CI 0.70, 0.96; p < 0.001). Furthermore, we observed the association when the Serum klotho was greater than 801 (OR = 0.94, 95%CI 0.89, 0.99; p = 0.035). The relationship between serum Klotho levels and all-cause mortality was U-shaped, while the relationship with cardiovascular mortality was L-shaped. Specifically, low serum Klotho levels were associated with an increase in all-cause mortality by 21% and cardiovascular mortality by 76% among patients with CKM syndrome. Furthermore, serum Klotho levels demonstrated excellent predictive efficacy for both the severity and mortality associated with CKM syndrome.

Conclusions: This study indicates that low serum Klotho levels serve as reliable indicators of both the severity of CKM syndrome and the associated risk of mortality.

Background: Childhood-onset systemic lupus erythematosus (cSLE) is associated with significant morbidity and mortality. Dyslipidemia and metabolic syndrome are recognized risk factors for premature atherosclerosis. This study aimed to determine the prevalence of dyslipidemia and metabolic syndrome, and to explore the relationships between lipid profiles, anthropometry, and disease status in cSLE.

Methods: This cross-sectional study was conducted at a university-based tertiary referral center from April 2023-March 2024. Patients aged 10-19 years with cSLE diagnosed before 18 years and at least 1 year follow-up were enrolled, excluding those with other autoimmune disorders, chronic kidney disease, infections, receiving lipid lowering drugs prior, and pregnancy. Demographic data, metabolic laboratory tests, disease status, dietary intake, anthropometry, and body composition via bioelectric impedance analysis were evaluated. The prevalence of dyslipidemia and metabolic syndrome were documented. Variables were compared between patients with and without dyslipidemia. Correlations between lipid profiles, metabolic laboratory variables, and SLE disease-related variables were explored.

Results: A total of 132 cSLE patients (94.7% female, mean age 11.6 ± 2.6 years) were included. Dyslipidemia was present in 48.5%, hypertriglyceridemia being the most common (28.8%); metabolic syndrome and hyperuricemia were present in 3.8% and 20.5%, respectively. Patients with dyslipidemia were significantly younger at cSLE diagnosis, had higher percentage of hypertension and active features of organ involvement, lower percentage of Lupus Low Disease Activity State, more use of mycophenolate mofetil and antihypertensive medications, higher uric acid level, higher waist circumference, body mass index, body mass index z-score, and fat mass (P < 0.05). Triglycerides, low-density lipoprotein cholesterol, and total cholesterol correlated positively with urine protein-to-creatinine ratio (r = 0.472, 0.469, and 0.591, respectively; P < 0.001) and negatively with serum albumin (r = -0.372, -0.506, and - 0.528, respectively; P < 0.001). Total cholesterol and low-density lipoprotein cholesterol correlated positively with cumulative prednisolone equivalent dose (rho = 0.350 and rho = 0.351, respectively, P < 0.001).

Conclusions: Nearly half of cSLE patients had dyslipidemia, especially those with younger age at diagnosis, higher body mass index, proteinuria, and suboptimal-controlled disease. Metabolic syndrome and hyperuricemia were present. Lipid profile assessment in early adolescents is recommended to identify metabolic comorbidities in cSLE.

Background: Previous studies have established a correlation between elevated levels of remnant cholesterol (RC) and the occurrence of type 2 diabetes mellitus (T2D) as well as insulin resistance (IR); however, the precise nature of these associations remains incompletely elucidated. This study aimed to evaluate the relationships between RC and IR, as well as RC and T2D, and to determine the extent to which IR mediated the relationship between RC and T2D.

Methods: This was an observational study that utilized cross-sectional methods to examine the general population in the National Health and Nutrition Examination Survey (NHANES) 1999-2020. The participants were divided into 4 groups according to the RC quartiles. The outcome was the prevalence of IR and T2D. Survey-weighted binary logistic regression analysis was used to analyze the associations, and the restricted cubic spline (RCS) curve was used to further analyze the nonlinear relationship. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic performance, and the areas under the curves (AUC) of RC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were compared using the DeLong test. The mediating effect of IR on the relationship between RC and T2D was evaluated through mediation analysis.

Results: A total of 23,755 participants (46.02 ± 18.48 years, 48.8% male) were included in our study. Higher RC levels were significantly associated with increased prevalence of both IR and T2D. After adjusting for potential confounders, logistic regression analysis showed that higher RC quartiles were associated with the increased prevalence of IR [Quartile 4 vs. Quartile 1: odds ratio (OR) (95% confidence interval, CI): 1.65 (1.41-1.94), p < 0.001] and T2D [Quartile 4 vs. Quartile 1: OR (95% CI): 1.24 (1.03-1.50), p = 0.024]. RCS analysis revealed two distinct nonlinear relationships: one between RC levels and the prevalence of IR (nonlinear p < 0.001), and another between RC levels and the prevalence of T2D (nonlinear p < 0.001). ROC curve analysis demonstrated that RC had the highest discriminative ability, significantly outperforming LDL-C, HDL-C, and TG in predicting both IR and T2D risk (all P < 0.001 by DeLong test). Mediation analysis revealed that IR significantly mediated the relationship between RC and T2D, with approximately 54.1% of the effect of RC on T2D being indirect through IR.

Conclusions: Higher RC level was associated with increased prevalence of IR and T2D. IR mediated 54.1% of the association between RC and T2D, suggesting that managing IR could be crucial in reducing the risk of T2D in individuals with elevated RC levels.

Background: Klotho, an anti-aging protein, is linked to energy metabolism. There is limited research on the association of serum klotho and triglyceride glucose (TyG) index-related indicators. Our research aims to investigate the relationship of serum klotho with TyG-BMI (body mass index), TyG-WC (waist circumference), and TyG-WHtR (waist-to-height ratio).

Methods: From 2007 to 2016, we examined 6,370 participants in the National Health and Nutrition Examination Survey (NHANES). The enzyme-linked immunosorbent assay (ELISA) was utilized to measure serum klotho. We calculated the TyG-BMI, TyG-WC, and TyG-WHtR based on fasting triglycerides, fasting glucose, BMI, WC, and WHtR. Multiple linear regression analysis was used to evaluate the association of serum klotho with TyG-BMI, TyG-WC, and TyG-WHtR. Additionally, generalized additive model (GAM) and smoothing curves were used to evaluate the linear and nonlinear relationships. A piecewise regression model was also utilized to test for threshold effects and determine the breakpoints. Finally, the potential independent associations of serum klotho with TyG-BMI, TyG-WC, and TyG-WHtR were further explored using subgroup analysis.

Results: We observed a statistically significant difference in serum klotho levels across different quartiles of the population. Based on the multiple linear regression analysis, serum klotho levels were negatively associated with TyG-related indicators. There was a nonlinear relationship between the serum klotho and TyG-BMI, TyG-WC, and TyG-WHtR. The segmented regression analysis revealed that the breakpoints of TyG-BMI, TyG-WC, and TyG-WHtR were 5.42, 6.67, and 1.89, respectively. Subgroup analysis showed that TyG-related indicators interacted with gender and diabetes.

Conclusions: In this study, a negative and nonlinear relationship was identified between serum klotho and TyG-related indicators. Further research is needed to clarify the potential mechanisms that may link serum klotho to TyG-BMI, TyG-WC, and TyG-WHtR.

Background: Resolvins, which are divided into series D (RvD) and E (RvE), originate from omega-3 fatty acids, DHA and EPA and were recently found to be involved in the modulation of inflammation in some tumors, including breast cancer (BC). We aimed to assess the resolvin profiles (RvD1, RvD2, RvD3 and RvE1) in the plasma of BC patients compared with those of controls and to determine differences in their concentrations according to BC presentation and immunohistochemical characteristics.

Methods: We considered BC patients (sporadic, familiar and BRCA1/2-mutated forms) naïve to any anticancer treatment and controls affected by nonmalignant breast disease. According to the BC immunohistochemical characteristics, we identified the luminal-A, luminal-B, HER2 + and triple-negative subtypes. The levels of RvD1, RvD2, RvD3 and RvE1 in the plasma of all the participants were measured via ELISA kits.

Results: We enrolled 64 women, 53 with BC (age 51 ± 10 y) and 11 controls (age 49 ± 7 y). Twenty-seven patients presented with sporadic BC, 16 with a positive history of BC (familiar), and 10 with BRCA 1/2 gene mutations. Compared with control patients, BC patients presented higher levels of RvD1 (p = 0.015), and no differences were detected for RvD2, 3 or RvE1. In BC, all resolvin levels were positively correlated with each other (p < 0.001). The expression of RvD1 and RvD3 was lower in the mutated group than in the familiar and sporadic groups (p < 0.05). The expression of RvD2 and RvE1 tended to be lower in the BRCA 1/2-mutated group than in the sporadic and familiar BC patients (p = 0.051 and p = 0.062, respectively). No differences in plasma resolvin levels were observed according to immunohistochemical characteristics (luminal A, luminal B, HER2+, triple-negative). However, RvD1 was lower in triple-negative patients than in patients with the other BC subtypes (p = 0.023). In terms of Ki-67 expression, RvD3 expression was lower in patients with high Ki-67 expression ([Formula: see text]20%) than in those with low Ki-67 expression (<20%) (p = 0.034).

Conclusion: This is the first human study profiling specific plasma resolvin levels in BC patients, which revealed low plasma levels of some resolvins in patients with BRCA1/2 mutations, triple-negative subtypes and high Ki-67 expression, potentially impacting treatment response and prognosis.