Lipids in Health and Disease最新文献

Objective: As emerging biomarkers for stroke risk, the clinical value of the atherogenic index of plasma and a body shape index has gained increasing attention. However, current research on their combined use for stroke risk stratification remains limited. This study aims to analyze the combined effects of Atherogenic Index of Plasma (AIP) and A Body Shape Index (ABSI) trajectories to explore their potential contribution to improving stroke risk prediction accuracy.

Methods: The study data were derived from the China Health and Retirement Longitudinal Study conducted between 2011 and 2018, ultimately including 4,942 participants with two AIP measurements and three ABSI measurements collected for each participant. AIP was classified using K-means clustering analysis, and cumulative AIP values were calculated. The latent class trajectory model was employed to identify characteristic ABSI trajectory patterns over time. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (95% CIs).

Results: The median follow-up duration in China Health and Retirement Longitudinal Study (CHARLS) was 3.0 years, during which 395 of 4,942 participants (7.99%) developed stroke. Adjusted multivariable Cox regression models demonstrated that both the high AIP clustering combined with high ABSI trajectory model (HR = 2.256, 95% CI: 1.346-3.781, P = 0.002) and the high cumulative AIP with high ABSI trajectory model (HR = 2.455, 95% CI: 1.514-3.983, P < 0.001) showed significant associations with stroke in their respective groups, with both associations remaining robust in sensitivity analyses. The AIP clustering combined with ABSI trajectory model exhibited the highest diagnostic performance for stroke (area under the receiver operating characteristic curve [AUC]: 0.612).

Conclusion: The combined prediction of AIP and ABSI enables earlier identification of stroke risk in the general population, demonstrating significant clinical value for stroke prevention and treatment.

Background: The relationship between vitamin D deficiency and the uric acid-to-high-density lipoprotein cholesterol ratio (UHR) in postmenopausal women remains unclear. This study aims to investigate the association between these variables and to evaluate the potential interaction between UHR and waist circumference (WC).

Methods: Data from 5,155 postmenopausal women who participated in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2016 were included in this cross-sectional investigation. Weighted regression analysis served as the primary methodology employed to examine the association between UHR and vitamin D deficiency. Furthermore, interaction analysis, sensitivity analysis, and restricted cubic splines (RCS) were also conducted.

Results: According to multivariate adjusted analysis, vitamin D deficiency was positively correlated with UHR (OR = 1.05, 95% CI 1.02-1.07). The risk of vitamin D deficiency in the highest quartile population of UHR was significantly higher than that in the lowest quartile population (OR = 1.75, 95% CI: 1.36-2.27). Serum 25-hydroxyvitamin D was negatively correlated with UHR (β= -0.74, 95% CI: -1- -0.47). Vitamin D deficiency has a linear dose-response relationship with UHR. In addition, the study also discovered the interaction between UHR and WC.

Conclusions: The UHR level in postmenopausal women is positively associated with vitamin D deficiency. Managing WC may contribute to reducing the risk of vitamin D deficiency in individuals with elevated UHR.

Metabolic diseases, a major challenge in global public health, are commonly characterized by insulin resistance, lipid metabolism disorders, and mitochondrial dysfunction, and their pathological processes are often accompanied by the abnormal accumulation of lipids in metabolically active tissues such as the liver, heart, and skeletal muscle. Recently, lipid droplets and mitochondria have been shown to interact with each other through membrane contact sites and play a central role in maintaining cellular metabolic homeostasis. The unique monolayer phospholipid membrane structure and formation process of lipid droplets, along with the double-membrane structure and diverse functions of mitochondria, together form the basis for their interaction. There are two modes of interaction, namely dynamic contact and stable anchoring, which are mediated by a variety of proteins to achieve efficient exchange and metabolic regulation of metabolites such as fatty acids. However, dysregulation of lipid droplet-mitochondria interactions initiates a pathogenic cascade involving fatty acid overload, increased reactive oxygen species generation, and mitochondrial dysfunction. These perturbations drive the pathogenesis of metabolic disorders. This review systematically summarizes the key pathological roles of dysregulated lipid droplet-mitochondrial interactions in globally prevalent metabolic diseases such as diabetes mellitus, metabolic dysfunction-associated fatty liver disease, and obesity. This in-depth analysis of molecular mechanisms clarifies the physiological basis of the regulation of lipid homeostasis in the body and provides a theoretical basis for developing novel therapeutic strategies for these diseases to alleviate the related growing global health burden.

Background: Obesity is a global health concern linked to metabolic disorders and gut microbiota dysbiosis, particularly under high-fat diet (HFD) conditions. This study explores the role of imidazole propionate (ImP), a histidine-derived microbial metabolite, in regulating lipid metabolism and the development of obesity.

Methods: Male C57BL/6 mice were fed either a chow diet or HFD for 15 weeks, followed by plasma metabolomic analysis, which revealed significant downregulation of ImP in obese mice. Functional assays were performed using zebrafish larvae and human adipocytes, with lipid accumulation assessed via Nile Red and Oil Red O staining. Transcriptomic sequencing and KEGG pathway analysis were used to investigate the underlying molecular mechanisms.

Results: ImP treatment notably reduced lipid accumulation in both zebrafish larvae and human adipocytes. RNA-seq and protein expression analyses revealed that ImP suppressed peroxisome proliferator-activated receptor (PPAR) pathway key components, such as FABP4, ACSL4, and CEBPα.

Conclusions: These findings demonstrate that ImP attenuates lipid accumulation by inhibiting the PPAR signaling pathway. As a gut microbial metabolite, ImP may offer therapeutic potential in preventing or treating HFD-induced obesity.

Background: Cardiovascular disease (CVD) has been documented to be related with the triglyceride glucose (TyG) index. However, limited research has explored the change in the triglyceride glucose-waist circumference (TyG-WC) index in relation to CVD, particularly among individuals with prediabetes and diabetes. Thus, this longitudinal analysis aimed to investigate the association between changes in the TyG-WC and CVD in patients with glucose dysregulation.

Methods: This study comprised 2428 individuals with prediabetes and diabetes, sourced from the China Health and Retirement Longitudinal Study (CHARLS) database. Using K-means clustering, three subgroups were identified based on their TyG-WC index trajectories. Additionally, the cumulative TyG-WC index was calculated and divided into tertiles (T1, T2, T3). Proportional hazards models were employed to examine the correlations between TyG-WC trajectories, cumulative TyG-WC tertiles, and the incidence of CVD during the follow-up period. Subgroup analyses were carried out to validate the robustness of the results.

Results: The incidence rates of CVD, cardiac events, and stroke were highest among patients with a high-stable TyG-WC, significantly reduced in the moderate-stable TyG-WC group, and lowest among participants with low-stable TyG-WC (all P for trend < 0.001). After adjusting for confounders, the risk of CVD was significantly associated with the TyG-WC trajectories and the cumulative TyG-WC tertiles. Compared to the low-stable group, the CVD risk for the moderate and high-stable groups were 1.266 (95% confidence interval [CI]: 1.009-1.589) and 1.639 (95% CI: 1.269-2.117), respectively (both P < 0.05). Furthermore, the risk of CVD, stroke, and cardiac events in T2 group and T3 group was significantly higher than that in T1 group (all P < 0.05). ROC curve analysis showed that compared with baseline waist circumference, TyG-WC and TyG, the cumulative TyG-WC demonstrated a relatively higher discriminative ability in assessing CVD.

Conclusion: The changes of TyG-WC are closely related to CVD among individuals with prediabetes and diabetes, which may serve as a novel indicator for the early detection of CVD risk in these populations.

Background: Recent studies highlighted the independent role of remnant cholesterol (RC) on the risk of atherosclerotic cardiovascular disease (ASCVD). We explored interrelationships among low-density lipoprotein cholesterol (LDL-C), RC, and ASCVD in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: Analyzing 25,418 MASLD and 57,501 non-MASLD ASCVD- free Chinese adults from the Kailuan Study (2006-2011), we used Fine-Gray models to evaluate LDL-C and RC associations with ASCVD across varying cut-offs, incorporating China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) 10-year risk.

Results: The MASLD group had comparable LDL-C but elevated RC levels compared to the non-MASLD. In MASLD individuals, associations of LDL-C (J-shaped) and RC (linear) with ASCVD were observed, contrasting with the monotonically increasing relationships in non-MASLD individuals. Even with guideline-recommended LDL-C levels, the MASLD group with elevated RC alone showed a higher ASCVD risk. Among individuals with low ASCVD risk evaluated by the China-PAR model, MASLD patients with LDL-C < 1.8 mmol/L and RC < 0.6 mmol/L had comparable ASCVD risk to the non-MASLD group with LDL-C < 3.4 mmol/L and RC < 0.6 mmol/L (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 0.55-2.47). For those with moderate to high predicted ASCVD risk, the MASLD with the same lipid levels (LDL-C < 1.8 mmol/L and RC < 0.6 mmol/L) had a similar risk of ASCVD to that of the non-MASLD with LDL-C < 2.6 mmol/L and RC < 0.6 mmol/L (HR: 1.15; 95% CI: 0.71-1.86).

Conclusions: The findings indicate that MASLD alters the relationship between lipids and ASCVD, underscoring the necessity for integrated and stricter management of both LDL-C and RC to mitigate risk in this population.

Background: Obesity and excessive body fat lead to metabolic and inflammatory disturbances. The fat mass index (FMI) has recently been recognized as a more sensitive measure of obesity than body mass index (BMI). Therefore, we investigated the relationship between higher FMI and alterations in platelet phospholipid fatty acid (FA) composition, oxidative stress, and inflammation.

Methods: Cross-sectional study of adults aged 18-49 years attended an outpatient clinic National Osteoporosis Center from May 2023 till June 2024, who agreed to participate in the study.

Exclusions: major chronic diseases, active cancer, pregnancy, weight-affecting medications, thyroid/adrenal disorders, and diabetes. The total body composition was assessed via DXA; FMI (kg/m²) was categorized as fat deficit, normal, excess fat, or obesity. Fasting blood was analysed for glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, CRP, and insulin; serum malondialdehyde (MDA) by HPLC; platelet phospholipid FA profile by GC/MS. FMI group differences were tested with Kruskal-Wallis and Mann-Whitney. The Spearman coefficient was used to evaluate the associations.

Results: The study included 169 participants (36.3 ± 6.25 years; 64.5% female). Across ascending FMI groups (fat-deficit to obesity), adverse metabolic shifts were observed: HDL-cholesterol declined from 1.8 to 1.3 mmol/L (p < 0.001), whereas triglycerides rose from 0.7 to 1.4 mmol/L (p < 0.001) and CRP from 0.3 to 2.4 mg/L (p < 0.001). In platelet phospholipid membrane, the proportion of polyunsaturated FAs increased with FMI (from 2.5% to 4.8%; p = 0.002), including ω3 (from 1.1% to 2.0%; p = 0.003) and ω6 (from 7.5% to 11.4%; p = 0.016). The ω6/ω3 ratio showed a weak positive association with LDL-cholesterol (ρ = 0.166; p = 0.040). Serum MDA increased across FMI groups (from 95.5 to 104.3 µg/L; p = 0.019) and correlated with the polyunsaturated FAs (ρ = 0.178, p = 0.027).

Conclusions: An elevated FMI is associated with altered platelet FA composition and increased OS. These changes may be early markers for metabolic and inflammatory dysregulations that underlie the pathogenesis of cardiometabolic risk. Moreover, platelet FA profiling could provide additional value for risk stratification in overweight individuals.

Background: Sarcopenia, the progressive depletion of skeletal muscle mass and strength, worsens daily living outcomes and survival in individuals diagnosed with cancer. It arises from complex interactions between primary malignancy, antineoplastic interventions, and treatment-related sequelae, making early risk assessment a clinical priority. The body roundness index (BRI), an anthropometric metric superior to body mass index in body composition profiling, has shown diagnostic utility across metabolic and cardiovascular domains. However, its prognostic value in cancer-associated sarcopenia remains underexplored. This bicontinental study pioneers the clinical validation of BRI for sarcopenia prediction, proposing an objective quantification framework to optimize early screening and personalized therapeutic strategies in oncological practice.

Methods: A cross-national dual-cohort design was implemented, using data from the US National Health and Nutrition Examination Survey multi-cancer cohort (n = 1,688) and a Chinese gastrointestinal oncology cohort (n = 713). Multivariable logistic regression adjusted demographics, lifestyle, comorbidities, cancer-related characteristics, and laboratory markers to examine the independent association between BRI and sarcopenia. Subgroup analyses with race- and cancer type-specific interaction terms were conducted to assess effect modification patterns, whereas nonlinear relationships were examined using smooth curve fitting and threshold effect models to identify critical thresholds. A predictive tool was developed and validated through receiver operating curve analysis and decision curve analysis to assess its diagnostic performance and clinical utility.

Results: BRI was positively associated with sarcopenia risk in both cohorts (US: odds ration [OR] = 1.62, 95% confidence interval [CI] = 1.48-1.77, P < 0.001; Chinese: OR = 2.39, 95% CI = 1.82-3.15, P < 0.001), with distinct threshold effects observed (US cohort critical BRI value = 6.73; Chinese cohort critical BRI value = 3.01). The predictive model showed good performance (US cohort area under the curve (AUC): 0.80 training, 0.82 validation; Chinese cohort AUC: 0.66 training, 0.78 validation). Decision curve analysis for both cohorts exhibited broad clinical applicability.

Conclusion: This study is the first to establish BRI independently predicts sarcopenia risk in patients with cancer. Additionally, a BRI-based model integrating sex and age combines the advantages of accuracy, specificity, and cost-effectiveness, demonstrating significant clinical utility.