Lipids are the most abundant biomolecules of human plasma, and their balance plays a significant role in health and disease management. Despite the importance of lipids, the studies focused on the comprehensive determination of the plasma lipidome in children are limited. In this study, we investigated the sex, age, and weight-specific changes in the plasma lipidome of nonfasting preadolescent children aged 9-12 years (n = 342) using a nontargeted liquid chromatography-mass spectrometry technique. A total of 219 lipid species were characterized in the plasma samples. Multivariate analysis revealed that boys and girls have similar lipid profiles, but relatively higher levels of capric acid-composed triacylglycerols (TGs) were observed in plasma samples of boys. Saturated fatty acids are the most abundant fatty acyls followed by mono- and polyunsaturated fatty acids in the plasma of both boys and girls. Sphingolipids such as ceramides, hexosylceramides, sphingomyelin, and a phospholipid (phosphatidylinositol) were relatively higher in the plasma of a 10-year-old group than other age groups. Plasma levels of TG and phosphatidylserine were increased within age from 9 to 12 years. Furthermore, most of the TG molecular species were increased in the plasma of overweight children compared to the normal range groups. The receiver operating characteristic analysis results show that TG (10:0/10:0/18:1) could be a specific marker for childhood obesity (area under the curve (AUC) = 0.72). Overall, this study highlights the altered plasma lipidome in preadolescent children for sex, age, and percentage of overweight. Early detection of lipid markers for obesity would be a promising target for developing therapeutic strategies.

Diabetic retinopathy (DR) is a diabetic microvascular complication and a leading cause of vision loss. However, there is a lack of effective strategies to reduce the risk of DR currently. The present study is aimed at assessing the causal effect of lipid-regulating targets on DR risk using a two-sample Mendelian randomization (MR) study. Genetic variants within or near drug target genes, including eight lipid-regulating targets for LDL-C (HMGCR, PCSK9, and NPC1L1), HDL-C (CETP, SCARB1, and PPARG), and TG (PPARA and LPL), were selected as exposures. The exposure data were obtained from the IEU OpenGWAS project. The outcome dataset related to DR was obtained from the FinnGen research project. Inverse-variance-weighted MR (IVW-MR) was used to calculate the effect estimates by each target. Sensitivity analyses were performed to verify the robustness of the results. There was suggestive evidence that PCSK9-mediated LDL-C levels were positively associated with DR, with OR (95% CI) of 1.34 (1.02-1.77). No significant association was found between the expression of HMGCR- and NPC1L1-mediated LDL-C levels; CETP-, SCARB1-, and PPARG-mediated HDL-C levels; PPARA- and LPL-mediated TG levels; and DR risk. This is the first study to reveal a genetically causal relationship between lipid-regulating drug targets and DR risk. PCSK9-mediated LDL-C levels maybe positively associated with DR risk at the genetic level. This study provides suggestive evidence that PCSK9 inhibition may reduce the risk of DR.

Gangliosides, sialic acid-containing glycosphingolipids, are abundant in cell membranes and primarily involved in controlling cell signaling and cell communication. The altered ganglioside pattern has been demonstrated in several neurodegenerative diseases, characterized during early-onset or infancy, emphasizing the significance of gangliosides in the brain. Enzymes required for the biosynthesis of gangliosides are linked to several devastating neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP). In this review, we summarized not only the critical roles of biosynthetic enzymes and their inhibitors in ganglioside metabolism but also the efficacy of treatment strategies of ganglioside to address their significance in those diseases.

Background Advanced lung cancer that contributes to a heavy burden on medical institutions is the leading cause of cancer-related death and is often accompanied by metabolic disorders. In this study, we aimed to explore the biomarkers of diagnosis and radiotherapy response in non-small-cell lung cancer (NSCLC) patients by plasma lipidomics analysis. Method Using triple-quadrupole mass spectrometer analysis, our research characterized the plasma lipid metabolomics profile of 25 healthy controls and 31 advanced NSCLC patients in each of three different radiotherapy phases. Results The results showed altered lipid elements and concentrations among NSCLC patients with different radiotherapy phases, NSCLC subtypes, and different radiotherapeutic responses. We found that compared to the healthy controls, myelin-associated glycoprotein (MAG), phosphatidylinositol (PI), and phosphatidylserine (PS) were mainly and significantly altered lipid elements (> twofold, and p < 0.05) among NSCLC patients with different radiotherapy phases. Through comparison of lipid elements between bad and good responses of NSCLC patients with radiotherapy, the obviously declined phosphatidylglycerol (PG 18 : 0/14 : 0, 18 : 1/18 : 3, and 18 : 0/20 : 1) or markedly elevated PI (20 : 0/22 : 5 and 18 : 2/22 : 4) and phosphatidic acid (PA 14 : 0/20 : 4, 14 : 0/20 : 3, and 18 : 2/22 : 4) could indicate poor therapeutic response for NSCLC patients. The results of ROC curve analysis suggested that PG (18 : 0/20 : 1 and 18 : 0/14 : 0) could clearly predict the radiotherapeutic response for NSCLC patients, and PS (18 : 0/20 : 0) and cholesterol were the first two lipid components with the most potential for the diagnosis of advanced NSCLC. Conclusion Our results indicated that plasma lipidomics profiling might have a vital value to uncover the heterogeneity of lipid metabolism in healthy people and advanced NSCLC patients with different radiotherapy phase, and further to screen out radiotherapeutic response-specific biomarkers.

Background: Identifying β-cells dysregulation in type 2 diabetes mellitus (T2DM) is crucial. Weight fluctuations are frequently observed during diabetes treatment. However, the relationship between body composition changes and islet β-cell function in individuals with T2DM remains insufficiently investigated. Methods: This retrospective longitudinal study encompassed a cohort of 775 T2DM patients, who underwent body composition measuring using dual-energy X-ray absorptiometry (DEXA) and followed up for a median of 2.29 years. Key metrics included body mass index (BMI), fat mass index (FMI), trunk fat mass index (TFMI), muscle mass index (MMI), appendicular skeletal muscle mass index (ASMI), muscle/fat mass ratio (M/F), and the appendicular skeletal muscle mass/trunk fat mass ratio (A/T) were then categorized and grouped. Insulin, C-peptide, and glucose levels were assessed concurrently following a glucose load. β-cell function included insulin resistance (HOMA-IR), insulin sensitivity (Matsuda index (MI)), and insulin secretion evaluated by HOMA-β and C-peptidogenic index (CGI). Results: Although no significant changes in BMI were observed, patients with T2DM at readmission exhibited higher FMI, TFMI, and ASMI, as well as elevated levels of HOMA-IR, MI, and CGI compared to baseline measurements. And lower MI, higher levels of CGI, and HOMA-IR were observed in BMI increased group. Univariate correlation analysis revealed a negative association between changes in BMI (ΔBMI) and ΔMI, while positive associations were observed in both ΔHOMA-IR and ΔCGI. Among body composition indexes, ΔFMI exhibited the strongest correlation with ΔHOMA-IR (r = 0.255, p < 0.001), and ΔASMI was positively associated with ΔMI and ΔCGI (r = 0.131 and 0.194, respectively). Moreover, increased levels of BMI and FMI were associated with a greater risk of progressive insulin resistance compared to the decreased, whereas the trend was converse in ASMI and A/T. Conclusions: Increased FMI may partially contribute to the deterioration of insulin resistance, while increased ASMI is associated with improved insulin sensitivity and secretion. Maintaining an appropriate BMI and muscle/fat ratio is conductive to prevent the progression of insulin resistance in patients with T2DM.

Triterpenoids have been identified as potential novel lipid-lowering drugs for the treatment of hypertriglyceridemia. This study investigated the potential antilipogenic and/or antilipolytic effects of two triterpenoids (ARM-2 and RA-5) isolated from the stem bark of Protorhus longifolia (Benrh.) Engl. Employing a combination of in silico predictions and in vitro assays, the interactions between these triterpenoids and key proteins involved in lipogenesis and lipolysis were investigated. In silico molecular docking analysis predicted a favourable binding affinity of both triterpenoids to PPARγ, SREBP-1, and AMPK, with lower binding affinity to C/EBPα, pancreatic lipase, and hormone-sensitive lipase (HSL). Both triterpenoids exhibited in vitro inhibition of pancreatic lipase with Ki and IC50 values ranging from 28.7 to 52.9 μM and 27.6 to 35.8 μM, respectively. Total and neutral lipid accumulation in differentiated 3T3-L1 adipocytes and the oleic acid-induced HepG2 cell model was inhibited, with ARM-2 showing better inhibition than RA-5. In the HepG2 model, the inhibitory activity of the two triterpenoids (at 25 and 100 μM) was comparable to 50 μM lovastatin, although the latter was cytotoxic, whereas both ARM-2 and RA-2 lacked cytotoxicity. Associated gene expression was similar to the effect of simvastatin where the expression of SREBP-1, PPARγ, C/EBPα, and HSL was reduced and that of AMPK was unchanged. In vitro studies confirmed that ARM-2 and RA-5 also inhibited adipocyte lipolysis, where the reduction in glycerol release by 25 and 100 μM was similar to 50 μM lovastatin and simvastatin. This study identifies that the triterpenoids, ARM-2 and RA-5, have the potential to modulate lipogenesis and lipolysis.

Thyroid hormone (TH) is essential for maintaining normal physiological processes during pregnancy, including the metabolism of energy materials in both the mother and fetus and the growth and development of fetal bone and nervous system. TH can act on the liver, fat, and other tissues and organs to participate in lipid synthesis and breakdown through multiple pathways. Consequently, abnormal thyroid function is often accompanied by lipid metabolism disorders. Both clinical and subclinical hypothyroidism, as well as dyslipidemia during pregnancy, have been shown to be associated with an increased risk of multiple adverse pregnancy outcomes. Recently, there has been an increased interest in studying the alteration of lipidomic and hypothyroidism (both clinical and subclinical hypothyroidism) during pregnancy. Studies have suggested that altered lipid molecules might be used as potential biomarker and associated with adverse maternal and neonatal outcome. Thus, we summarized the associations between lipid metabolism and clinical or subclinical hypothyroidism during pregnancy in this review. Then, we discussed the underlying mechanisms of thyroid dysfunction and lipid metabolism. In addition, we reviewed the possible effect of dyslipidemia on pregnancy and neonatal outcome. However, the relationship between hypothyroidism during pregnancy and changes in the lipid profile and how to intervene in the occurrence and development of adverse pregnancy outcomes require further study.

Paternal exposure to high-fat diets or individual fatty acids (FAs) including arachidonic acid (AA) modifies progeny traits by poorly understood mechanisms. Specific male reproductive system FAs may be involved in paternal inheritance, as they can modify a range of cellular components, including the epigenome. Our objective was to determine FAs in compartments of the male reproductive system that potentially affect ejaculate composition-right and left testicular interstitial fluid (TIF), vesicular gland fluid (VGF), and epididymal adipose tissue (EAT)-in mice exposed to AA or vehicle daily for 10 days (n = 9-10/group). Whole blood (WB) and interscapular brown adipose tissue (IBAT) FA profiles were used as reference. AA significantly affected only VGF FAs relative to vehicle, that is, increased and decreased levels of arachidic and docosahexaenoic acid, respectively, versus vehicle (0.28% ± 0.01% and 0.23% ± 0.03%, respectively, p = 0.049, and 2.42% ± 0.47% and 3.00% ± 0.58%, respectively, p = 0.041). AA affected distinct FAs in WB. Additionally, we uncovered AA-dependent and AA-independent FA laterality. Myristic acid was higher in AA-exposed left versus right TIF (0.68% ± 0.35% and 0.60% ± 0.11%, respectively, p = 0.004). Right TIF contained higher oleic and linoleic acid and lower stearic acid than left TIF (29.01% ± 3.07% and 24.00% ± 2.18%, respectively, p = 0.005; 9.14% ± 1.88% and 7.05% ± 1.36%, respectively, p = 0.005; and 21.90% ± 2.92% and 26.01% ± 2.46%, respectively, p = 0.036), irrespective of exposure to AA. The TIF oleic/stearic acid ratio suggested higher Stearoyl-CoA Desaturase 1 activity in the right versus the left testis (1.35 ± 0.32 and 1.00 ± 0.17, respectively, p = 1.0 × 10-4). Multitissue comparisons revealed that TIF and VGF FA profiles were distinct from WB, EAT, or IBAT counterparts, suggesting tissue-specific FA fingerprints. In conclusion, AA modulated selected VGF long-chain FAs that may impact on uterine inflammation and subsequent embryonic development. AA altered local FA synthesis or selective uptake, rather than eliciting passive uptake from WB. Additionally, we uncover a significant laterality of testis FAs that may result in asymmetric sperm cell phenotypes.