Editorial: The role of lipids in relation to preventing inflammation and chronic diseases

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Despite substantial advances in pharmaceutical treatments targeting inflammation and the chronic non-communicable diseases (NCDs) associated with it, these conditions continue to cause considerable morbidity and mortality worldwide. NCDs, including cardiovascular disease (CVD), cancer, obesity, type 2 diabetes mellitus (T2DM), metabolic syndrome, and stroke, remain the leading causes of ill health and premature death. Indeed, CVD alone is responsible for over 18 million deaths annually, while cancer and obesity claim 10 million and 4.7 million deaths, respectively. These figures highlight the profound societal and healthcare burden of chronic illness. In recent years, chronic low-grade systemic inflammation has been increasingly recognised as a key contributor to the development and progression of many noncommunicable diseases (NCDs). Addressing the mechanisms underlying systemic inflammation may therefore offer important opportunities for the prevention and management of these conditions. In spite of therapeutic advances, treatments often show variable effectiveness, underscoring the need for a deeper understanding of the mechanisms of NCDs.Lipids have been long recognized as structural and energy-storing molecules; today bioactive lipids regulate inflammatory and immune responses through multiple signalling pathways. and Japanese (n = 12,489) cohorts, stratified by CMRF status. The association between RC and diabetes mellitus (DM) was assessed using Cox regression models, restricted cubic splines (RCS), extreme gradient boosting (XGboost), receiver operating characteristic (ROC) analysis, and mediation analysis. RC was significantly associated with DM only in individuals with CMRF in both cohorts, and the association was nonlinear. Their study found also differences between the two cohorts: RC showed better predictive performance compared to LDL-C and total cholesterol in predicting DM risk among individuals with CMRF (AUC 0.606 and 0.647 in Chinese and Japanese cohorts, respectively). CMRF mediated 76.3 and 66.3% of the RC-DM association in the Chinese and Japanese cohorts. Their conclusion was that RC is nonlinearly associated with the incidence of DM in individuals with CMRF, primarily promoting its onset through the presence of CMRF.Emerging evidence also indicates that remnant cholesterol (RC) and inflammation play a crucial role in diabetic kidney disease (DKD) pathogenesis. Xie et al. investigated the association and diagnostic efficacy of remnant cholesterol inflammatory index (RCII), integrating RC and inflammatory markers, with DKD. They found both overall and nonlinear positive correlations between the risk of DKD and both RC (P for overall <0.001, P for nonlinear = 0.049) and RCII (P for overall <0.001, P for nonlinear <0.001). Also, machine learning models incorporating RCII and traditional risk factors demonstrated robust diagnostic efficacy, with extreme gradient boosting (XGBoost) achieving the highest AUC values in the testing set (AUC: 0.953). Given that RCII is a novel and promising biomarker for DKD risk, they suggested that its integration into diagnostic models may enhance early identification and personalized prevention strategies for DKD.An independent study conducted by Xie et al. investigated whether RC can be a novel risk factor for osteoarthritis (OA). They carried out a large prospective cohort of middle-aged and older adults; where RC showed a positive, dose-response association with incident osteoarthritis that attenuated to near-null after adjustment for BMI. Mediation analysis indicated that approximately 84% of the total association operated via BMI, supporting adiposity as the principal pathway and suggesting limited BMI-independent effect of RC. Their results highlighted that RC is potential modifiable metabolic biomarker and underscore the interplay of dyslipidemia and obesity in OA pathogenesis, suggesting that RC management combined with weight control may offer an effective strategy for OA prevention.In another study under the theme on how RC is implicated to a number of CD, Ren et al. studied the association of plasma remnant cholesterol with cognitive function in the middleaged and elderly Chinese adults with type 2 diabetes in a cross-sectional study. They recruited one thousand eight hundred seventeen participants aged 55 to 75 were from communities in Beijing. Demographic information and daily dietary intakes were collected by self-designed questionnaire. Fasting venous blood was obtained for quantitative analysis of plasma lipid parameters. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. They identified that an increase in plasma RC level is a potential risk factor for MCI.A plasma RC concentration below 0.578 mmol/L can decrease the risk of MCI in middle-aged and older individuals with T2DM. In a similar pattern, a plasma RC concentration below 0.581 mmol/L may lower the risk of MCI in non-T2DM subjects. The daily consumption of vegetables and legumes could help reduce the concentration of RC.Collectively, these studies demonstrate that RC is not only associated with CVD, but it is also associated with risk of T2DM, diabetic kidney disease, osteoarthritis, and cognitive decline. Collectively, these findings reinforce the concept that remnant lipoproteins are more than passive lipid carriers, instead acting as important mediators of cardiometabolic dysfunction and inflammation.Staying with the theme of lipoproteins, the role of high-density lipoproteins (HDL) in NCDs was also a examined in this Research Topic. Geng et al. investigated the association between HDL subfractions and long-term major adverse cardiac and cerebrovascular events (MACCEs) in patients with acute myocardial infarction (AMI). During a median follow-up of 52.4 months, 132 MACCEs (10.7%) occurred. Patients in the highest HDL-3 tertile had a lower MACCEs incidence than those in the lowest tertile (6.7% vs. 16.4%, p < 0.001). Higher HDL-3 levels were associated with improved event-free survival (HR = 0.58, 95% CI: 0.37-0.91) and demonstrated discriminative ability for MACCE risk (AUC = 0.62; 95% CI: 0.57-0.67), whereas HDL-C and HDL-2b were not significant. The levels of HDL-3 levels were independently associated with a higher long-term risk of MACCEs in AMI patients. Thus, HDL-3 may represent a potential biomarker for residual cardiovascular risk stratification and a potential therapeutic target for improving post-infarction outcomes. for metabolic dysfunction-associated steatotic liver disease (MASLD) and its progression to hepatocellular carcinoma was discussed. MASLD is currently the leading cause of chronic liver disease worldwide and a major cause of hepatocellular carcinoma (HCC), a cancer with poor prognosis. Considering the immense public health impact of MASLD and MASLD-HCC, preventive and more effective management strategies for these diseases are urgently needed.Their review discussed the role of PUFAs, more specifically n-3 and n-6, in MASLD and MASLD-HCC, by critically reviewing evidence from human clinical and observational studies, and experimental models.On another study of PUFAs in health, Huang et al. examined whether omega-6/omega-3 fatty acid ratio (O6:O3) measured by nuclear magnetic resonance (NMR) spectroscopy can improve cardiovascular risk prediction. The plasma O6:O3 ratio, a marker of inflammatory balance, is a promising biomarker for risk stratification. Therefore, they aimed to evaluate if adding the O6:O3 ratio to the SCORE2 model improves the prediction of major adverse cardiovascular events (MACE). They compared the predictive performance of the SCORE2 model with and without the O6:O3 ratio in an independent validation cohort (N = 54,940) using Harrell's C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).They concluded that incorporating the plasma O6:O3 PUFA ratio can provide a modest but statistically significant improvemen

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