The impact of overweight on lipid phenotype in different forms of dyslipidemia: a retrospective cohort study.

PURPOSE: Dyslipidemia plays a pivotal role in increasing cardiovascular risk. In clinical practice the misleading association between altered lipid profile and obesity is common, therefore genetically inherited dyslipidemias may not completely be addressed among patients with overweight. Thus, we aim to investigate the influence of overweight and obesity on the lipid phenotype in a cohort of patients with different forms of dyslipidemia. METHODS: A retrospective analysis was conducted on patients with dyslipidemia from 2015 to 2022. Patients were stratified in familial hypercholesterolemia (FH), familial combined hyperlipidemia (FCHL), non-familial hyperlipidemia or polygenic hypercholesterolemia (PH). Clinical characteristics and lipid profile were evaluated. RESULTS: Of the total of 798 patients, 361 were affected by non-familial hyperlipidemia (45.2%), while FCHL, FH and PH was described in 19.9%, 14.0% and 20.9% of patients, respectively. Overweight prevalence was higher in FCHL and non-familial hyperlipidemia patients than FH and PH patients. Subjects with overweight and obesity were independently associated with lower levels of high-density lipoprotein cholesterol (HDL-C) compared to patients with normal weight (52.4 and 46.0 vs 58.1, respectively; p < 0.0001); levels of triglycerides (TG) and non-HDL-C were higher in patients with overweight and obesity than patients with normal weight (257.3 and 290.9 vs 194.8, and 221.5 and 219.6 vs 210.1, p < 0.0001 and p = 0.01, respectively), while no differences were observed between patients with overweight and obesity. CONCLUSION: While dyslipidemias can be influenced by various factors, an important determinant may lie in genetics, frequently acting as an underlying cause of altered lipid profiles, even in cases of overweight conditions.

A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma.

Melanoma is the deadliest form of skin cancer due to its ability to colonize distant sites and initiate metastasis. Although these processes largely depend on the lipid-based cell membrane scaffold, our understanding of the melanoma lipid phenotype lags behind most other aspects of this tumor cell. Here, we examined a panel of normal human epidermal and nevus melanocytes and primary and metastatic melanoma cell lines to determine whether distinctive cell-intrinsic lipidomes can discern non-neoplastic from neoplastic melanocytes and define their metastatic potential. Lipidome profiles were obtained by UHPLC-ESI mass-spectrometry, and differences in the signatures were analyzed by multivariate statistical analyses. Significant and highly specific changes in more than 30 lipid species were annotated in the initiation of melanoma, whereas less numerous changes were associated with melanoma progression and the non-malignant transformation of nevus melanocytes. Notably, the "malignancy lipid signature" features marked drops in pivotal membrane lipids, like sphingomyelins, and aberrant elevation of ether-type lipids and phosphatidylglycerol and phosphatidylinositol variants, suggesting a previously undefined remodeling of sphingolipid and glycerophospholipid metabolism. Besides broadening the molecular definition of this neoplasm, the different lipid profiles identified may help improve the clinical diagnosis/prognosis and facilitate therapeutic interventions for cutaneous melanoma.

In situ detecting changes in membrane lipid phenotypes of macrophages cultured in different cancer microenvironments using mass spectrometry.

Macrophages, the important cells of immune system, have exhibited distinct gene phenotypes with diverse functions in different microenvironments. In the present study, macrophages RAW264.7 (M0 macrophages) and lipopolysaccharide (LPS) plus interferon gamma (INF-γ)-treated M0 macrophages (M1 macrophages) were cultured in different lung cell-derived culture supernatants (CSs) as imitative tumor microenvironments. The lipids (mainly from cell membrane) of intact macrophages were in situ detected by matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry. Approximately 300 of small molecules were observed in negative ion mode. Partial least square-discriminant analysis (PLS-DA) suggested that two types of the macrophages have different membrane lipid phenotypes. Changes in the levels of phosphatidylethanolamine PE(16:1/18:0), PE(18:1/18:0), PE(36:2), PE-Cer(d36:1), and PE(P-16:0/18:1) were closely associated with membrane phenotypes of macrophages. The heatmap also revealed that directional induction to classically activated macrophages (M1 macrophages) in vitro had greater impact on the membrane lipid phenotypes of macrophages than different lung cell-derived CSs. The results are consistent with the data obtained by biological technologies.

Lipid phenotypes in patients with nonalcoholic fatty liver disease.

OBJECTIVE: There has been conflicting evidence regarding the role of single lipid species in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to explore the associations between dyslipidemia phenotypes (combinations of lipid parameters) and the risk of NAFLD. METHODS: We conducted a cross-sectional analysis using a cohort of 9560 apparently healthy Chinese adults who underwent comprehensive health checkups including abdominal ultrasonography. RESULTS: Of 3709 participants with NAFLD, 41.8% were classified as normolipemia (NL), 3.8% as combined hyperlipidemia, 3.2% as hypercholesterolemia, 17.7% as dyslipidemia of metabolic syndrome (MetS), 10.2% as isolated low high-density lipoprotein cholesterol (HDL-C), and 23.3% as isolated hypertriglyceridemia. The multivariable-adjusted odds ratios (ORs) (with 95% confidence intervals) for NAFLD in those with combined hyperlipidemia, those with hypercholesterolemia, those with MetS dyslipidemia, those with low HDL-C, and those with hypertriglyceridemia compared with those with NL were 4.79 (3.19-7.20), 1.26 (0.94-1.69), 3.31 (2.74-3.99), 1.13 (0.95-1.34), and 2.63 (2.26-3.08), respectively. The associations between combined hyperlipidemia, MetS dyslipidemia, or hypertriglyceridemia and risk of NAFLD were consistently seen in various evaluated subgroups. The interactions between lipid phenotypes and sex, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), or uric acid (UA) were not significant for NAFLD (all P>0.05). CONCLUSIONS: There were diverse dyslipidemia phenotypes in patients with NAFLD. Combined hyperlipidemia, MetS dyslipidemia, and hypertriglyceridemia were strongly and independently associated with increased risk of NAFLD. Gender, BMI, BP, FPG, and UA status did not modify the associations between dyslipidemia phenotypes and NAFLD.