Serum lipids are associated with nonalcoholic fatty liver disease: a pilot case-control study in Mexico.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and cirrhosis. NAFLD is mediated by changes in lipid metabolism and known risk factors include obesity, metabolic syndrome, and diabetes. The aim of this study was to better understand differences in the lipid composition of individuals with NAFLD compared to controls, by performing direct infusion lipidomics on serum biospecimens from a cohort study of adults in Mexico. METHODS: A nested case-control study was conducted with a sample of 98 NAFLD cases and 100 healthy controls who are participating in an on-going, longitudinal study in Mexico. NAFLD cases were clinically confirmed using elevated liver enzyme tests and liver ultrasound or liver ultrasound elastography, after excluding alcohol abuse, and 100 controls were identified as having at least two consecutive normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (< 40 U/L) results in a 6-month period, and a normal liver ultrasound elastography result in January 2018. Samples were analyzed on the Sciex Lipidyzer Platform and quantified with normalization to serum volume. As many as 1100 lipid species can be identified using the Lipidyzer targeted multiple-reaction monitoring list. The association between serum lipids and NAFLD was investigated using analysis of covariance, random forest analysis, and by generating receiver operator characteristic (ROC) curves. RESULTS: NAFLD cases had differences in total amounts of serum cholesterol esters, lysophosphatidylcholines, sphingomyelins, and triacylglycerols (TAGs), however, other lipid subclasses were similar to controls. Analysis of individual TAG species revealed increased incorporation of saturated fatty acyl tails in serum of NAFLD cases. After adjusting for age, sex, body mass index, and PNPLA3 genotype, a combined panel of ten lipids predicted case or control status better than an area under the ROC curve of 0.83. CONCLUSIONS: These preliminary results indicate that the serum lipidome differs in patients with NAFLD, compared to healthy controls, and suggest that assessing the desaturation state of TAGs or a specific lipid panel may be useful clinical tools for the diagnosis of NAFLD.

Biomarkers of mammographic density in premenopausal women.

BACKGROUND: While mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women. We applied targeted metabolomics to identify circulating metabolites specifically associated with mammographic density in premenopausal women. Then, we aimed to identify potential correlates of these biomarkers to guide future research on potential modifiable determinants of mammographic density. METHODS: A total of 132 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, hexose) were measured by tandem liquid chromatography/mass spectrometry in plasma samples from 573 premenopausal participants in the Mexican Teachers' Cohort. Associations between metabolites and percent mammographic density were assessed using linear regression models, adjusting for breast cancer risk factors and accounting for multiple tests. Mean concentrations of metabolites associated with percent mammographic density were estimated across levels of several lifestyle and metabolic factors. RESULTS: Sphingomyelin (SM) C16:1 and phosphatidylcholine (PC) ae C30:2 were inversely associated with percent mammographic density after correction for multiple tests. Linear trends with percent mammographic density were observed for SM C16:1 only in women with body mass index (BMI) below the median (27.4) and for PC ae C30:2 in women with a BMI over the median. SM C16:1 and PC ae C30:2 concentrations were positively associated with cholesterol (total and HDL) and inversely associated with number of metabolic syndrome components. CONCLUSIONS: We identified new biomarkers associated with mammographic density in young women. The association of these biomarkers with mammographic density and metabolic parameters may provide new perspectives to support future preventive actions for breast cancer.

Metabolic Disturbances Identified in Plasma Samples from ST-Segment Elevation Myocardial Infarction Patients.

ST-segment elevation myocardial infarction (STEMI) is the most severe form of myocardial infarction (MI) and the main contributor to morbidity and mortality caused by MI worldwide. Frequently, STEMI is caused by complete and persistent occlusion of a coronary artery by a blood clot, which promotes heart damage. STEMI impairment triggers changes in gene transcription, protein expression, and metabolite concentrations, which grants a biosignature to the heart dysfunction. There is a major interest in identifying novel biomarkers that could improve the diagnosis of STEMI. In this study, the phenotypic characterization of STEMI patients (n = 15) and healthy individuals (n = 19) was performed, using a target metabolomics approach. Plasma samples were analyzed by UPLC-MS/MS (ultra-high-performance liquid chromatography-tandem mass spectrometry) and FIA-MS (MS-based flow injection analysis). The goal was to identify novel plasma biomarkers and metabolic signatures underlying STEMI. Concentrations of phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, and biogenic amines were altered in STEMI patients in relation to healthy subjects. Also, after multivariate analysis, it was possible to identify alterations in the glycerophospholipids, alpha-linolenic acid, and sphingolipid metabolisms in STEMI patients.

HDL-sphingomyelin reduction after weight loss by an energy-restricted diet is associated with the improvement of lipid profile, blood pressure, and decrease of insulin resistance in overweight/obese patients.

BACKGROUND: Sphingomyelin (SM) diminishes the fluidity of the surface monolayer of high-density lipoproteins (HDL), affecting their intravascular metabolism and antiatherogenic properties. Since overweight is associated with an altered HDL structure, weight loss may result in changes in HDL subclasses, particularly in their SM content. Therefore, we determined the plasma SM concentrations associated to both total HDL and HDL subclasses after weight loss in obese patients. METHODS: Fifty overweight patients, 40 women and 10 men, aged 38.6±6.4 y, were given an energy-restricted diet according to their sex, age, and height. No physical activity was prescribed. Plasma SM concentrations of HDL subclasses were determined by a gel surface method developed for this study. Cholesterol of HDL subclasses was also determined by enzymatic methods performed on a gel surface. RESULTS: Mean weight lost was 3.5±0.4 kg after 6 weeks of dietary intervention. As expected, insulin resistance and blood pressure decreased whereas lipid profile improved, except for HDL-cholesterol. SM in plasma and in all HDL subclasses significantly decreased after intervention. The magnitude of HDL-SM reduction was statistically associated with the amelioration of the components of the metabolic syndrome; the reduction of BMI explained the decrement of HDL-SM in a multivariate analysis. CONCLUSION: HDL-SM decreased after weight loss by an energy-restricted diet. Further, the association of this decrement with the improvement of blood pressure, lipid profile and the decrease of insulin resistance, was statistically significant; all HDL subclasses were similarly affected. Whether a reduction in HDL-SM contributes to the cardiovascular benefits of weight loss remains to be elucidated.

Folate intake and the MTHFR C677T genotype influence choline status in young Mexican American women.

Numerous studies have reported a relationship between folate status, the methylenetetrahydrofolate reductase (MTHFR) 677C-->T variant and disease risk. Although folate and choline metabolism are inter-related, only limited data are available on the relationship between choline and folate status in humans. This study sought to examine the influences of folate intake and the MTHFR 677C-->T variant on choline status. Mexican-American women (n=43; 14 CC, 12 CT and 17 TT) consumed 135 microg/day as dietary folate equivalents (DFE) for 7 weeks followed by randomization to 400 or 800 microg DFE/day for 7 weeks. Throughout the study, total choline intake remained unchanged at approximately 350 mg/day. Plasma concentrations of betaine, choline, glycerophosphocholine, phosphatidylcholine and sphingomyelin were measured via LC-MS/MS for Weeks 0, 7 and 14. Phosphatidylcholine and sphingomyelin declined (P=.001, P=.009, respectively) in response to folate restriction and increased (P=.08, P=.029, respectively) in response to folate treatment. The increase in phosphatidylcholine occurred in response to 800 (P=.03) not 400 (P=.85) microg DFE/day (week x folate interaction, P=.017). The response of phosphatidylcholine to folate intake appeared to be influenced by MTHFR C677T genotype. The decline in phosphatidylcholine during folate restriction occurred primarily in women with the CC or CT genotype and not in the TT genotype (week x genotype interaction, P=.089). Moreover, when examined independent of folate status, phosphatidylcholine was higher (P<.05) in the TT genotype relative to the CT genotype. These data suggest that folate intake and the MTHFR C677T genotype influence choline status in humans.

Major plasma lipids and fatty acids in four HDL mammals.

Lipid classes and their fatty acids were compared in plasma from four mammals: a laboratory rodent, the mouse; two domestic animals, the cat and dog; and a wild animal, the South American armadillo, Chaetophractus villosus. In all, the most abundant lipoprotein was high-density lipoprotein (HDL). In the total lipid of plasma, phospholipids (PL) predominated in all four species, in correlation with the proportion of HDL, both being largest in dogs. The major PL was phosphatidylcholine (PC), followed by sphingomyelin (SM) and lysophosphatidylcholine. The total plasma lipid from the four species contained long-chain n-6 polyunsaturated fatty acids as the predominant acyl groups, followed by comparable proportions of total saturated and monoenoic fatty acids and small percentages of n-3 PUFA. The percentages of these four major groups of fatty acids in PC, SM, triacylglycerols and cholesterol esters were similar among species, but showed significant differences in the ratios between major individual fatty acids composing these groups.

Plasma phospholipid fatty acids in X-linked adrenoleukodystrophy.

Blood cell and plasma lipid classes and their fatty acids were analyzed in a child with X-linked adrenoleukodystrophy. The increase in saturated fatty acids with very long chains typical of this disease occurred almost exclusively in sphingomyelin. In this lipid, the proportion of lignoceric (24:0) and hexacosanoic (26:0) acids increased while that of 18:0, 20:0, and 24:1 decreased. In the rest of the lipid classes, but especially in cholesteryl esters and triacylglycerols, the proportion of linoleate (18:2) decreased while that of oleate (18:1) increased. In glycerophospholipids, polyunsaturated fatty acids such as 20:4n-6, 22:5n-6, and 22:6n-3 were reduced while their immediate precursors, 20:3n-6, 22:4n-6, and 22:5n-3, respectively, were relatively increased, suggesting a defect in fatty acid desaturation mechanisms. Although less pronounced, a similar trend of changes was seen in the patient's mother; in both, all alterations were more marked in serum than in blood cells.