There is a growing need both clinically and experimentally to improve the characterization of blood lipids. A liquid chromatography-mass spectrometry (LC-MS) method, developed for qualitative semiquantitative detection lipids in biological samples previously validated mitochondrial samples, was now evaluated profiling serum Data were acquired using high-resolution, full scan MS high-energy, collisional dissociation (HCD), all ion fragmentation. The method designed efficient separation...

A liquid chromatography−mass spectrometry (LC−MS) method was used for separation of lipid classes as well both qualitative and semiquantitative detection individual lipids in biological samples. Data were acquired using high-resolution full-scan MS high-energy collisional dissociation (HCD) all ion fragmentation. The evaluated efficient positive negative ionization mode standards spanning six classes. Platform linearity robustness, related to the mitochondrial cardiolipin (CL), assessed...

Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can DNA, however the potential acute or chronic modulate cellular and/or organismal remains largely unexplored. We modeled genotoxic stress using a repair-deficient Csa-/-|Xpa-/- mouse model CS. Exogenous was in mice vivo primary cells vitro treated with different genotoxins giving rise diverse...

Lipidomics requires the accurate annotation of lipids in complex samples to enable determination their biological relevance. We demonstrate that unintentional in-source fragmentation (ISF, common lipidomics) generates ions have identical masses other lipids. Lysophosphatidylcholines (LPC), for example, generate fragments with same mass as free fatty acids and lysophosphatidylethanolamines (LPE). The misannotation true is particularly insidious matrixes since most are initially unannotated...

Robust methodologies for the analysis of fecal material will facilitate understanding gut (patho)physiology and its role in health disease help improve care individual patients, especially high-risk populations, such as premature infants. Because lipidomics offers a biologically analytically attractive approach, we developed simple, sensitive, quantitatively precise method profiling intact lipids material. The utilizes two separate, complementary extraction chemistries, dichloromethane (DCM)...

The increased presence of synthetic trans fatty acids into western diets has been shown to have deleterious effects on physiology and raising an individual's risk developing metabolic disease, cardiovascular stroke. importance these for health the diversity their (patho) physiological suggest that not only should free be studied but also monitoring fats side chains biological lipids, such as glycerophospholipids, is essential. We developed a high resolution LC-MS method quantitatively...

Abstract Aging alters the amplitude and phase of centrally regulated circadian rhythms. Here we evaluate whether peripheral rhythmicity in plasma lipidome is altered by aging through retrospective lipidomics analysis on samples collected 24 healthy individuals (9 females; mean ± SD age: 40.9 18.2 years) including 12 younger (4 females, 23.5 3.9 middle-aged older, (5 58.3 4.2 every 3 h throughout a 27-h constant routine (CR) protocol, which allows separating evoked changes from endogenously...

The interaction of dietary fats and carbohydrates on liver mitochondria were examined in male FBNF1 rats fed 20 different low-fat isocaloric diets. Animal growth rates mitochondrial respiratory parameters essentially unaffected, but mass spectrometry-based lipidomics profiling revealed increased levels cardiolipins (CLs), a family phospholipids essential for structure function, saturated or trans fat-based diets with high glycemic index. These showed elevated monolysocardiolipins (a CL...

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) block apoptotic neuronal cell death and are strongly neuroprotective in acute chronic neurodegeneration. Theoretical considerations, indirect data, consideration of parsimony lead to the hypothesis that modulation mitochondrial pathway(s) underlies at least some effects n-3 PUFAs. We therefore systematically tested this on healthy male FBFN1 rats fed for four weeks with isocaloric, 10% fat-containing diets supplemented 1, 3, or fish oil (FO)....

ABSTRACT Metabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this study, we employed an electrochemistry-based targeted metabolomics platform assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, Cognitive Behavior Therapy (CBT) 163 treatment-naïve outpatients with major depressive disorder. Serum samples from baseline 12 weeks post-treatment were analyzed using liquid...

Cardiolipins (CLs) are a family of phospholipids essential for mitochondrial structure and function. The defective remodeling the CL molecules (i.e., changing fatty acyl [FA] composition) has been linked to human pathology. We examined diet‐mediated changes in liver mitochondria from healthy male FBNF1 rats fed 24 different low‐fat, isocaloric diets. Growth rates respiratory parameters were essentially unaffected, but mass spectrometry‐based, lipidomics profiling revealed up‐regulation CLs...

Dietary or caloric restriction (DR) is the most potent and reproducible known means of reducing cancer risk in mammals. We have developed serum metabolomic profiles that can identify ad libitum fed caloric-restricted rats with a high degree accuracy. These are being adapted for use human epidemiology studies, given increased disease associated excess weight. Partial Least Squares Projection to Latent Structures Discriminant Analysis (PLS-DA), projection method optimized class separation...

Elevated circulating triglyceride (cTG) levels are an established risk factor for metabolic and cardiovascular disease. cTG populations respond to diet reflect physiological status, but specific linkages with many clinically‐relevant dietary factors remain unclear and/or controversial. We examined –and partially resolved ‐ several controversial links between fats/carbohydrates cTGs using a healthy, non‐obese rat model eliminate influence of Rats were fed one 20 isocaloric, low‐fat diets...

Weight loss is inherently linked to the utilization of stored fats and should be detectable as changes in blood lipidome. Such lipid may serve biomarkers reveal protective responses, eg, markers associated with insulin resistance or risk type II diabetes. Conversely, fat biased, at least initially, towards metabolism unsaturated vs saturated fats, which could have important public health consequences, acute weight‐loss might a period exposure conditions that favor atherosclerosis...

Methodologies for the analysis of intact lipids from fecal matter will facilitate understanding gut (patho)physiology, its role(s) in health and disease help improve patient care. Because are central to intestinal biology, more stable than many metabolites, conserved across microbiota proteins, they provide information relevant microbiome, host, environment. We developed a extraction method that utilizes two separate, complementary chemistries, dichloromethane methyl tert‐butyl...

High-content screening (HCS) has catalyzed drug development through enabling fast, large-scale, and reproducible testing of changes in cellular invitro models response to different types perturbations. One HCS approach, known as Cell Painting (CP), can conduct the morphological profiling images containing cells perturbed with treatments quantitatively assess complex biological changes. Profiling stages macrophage polarization, particular, enables new discovery disease-relevant conditions. To...

Caloric restriction (CR) robustly increases longevity/reduces morbidity in mammals, eg., breast cancer risk is generally decreased >90% CR rodents. usually dominant to other factors and are directly analogous human data linking obesity with poor health outcomes, including cancer. We tested if biomarkers of diet rats predicts future disease humans. Methods Metabolomics measurements sera/plasma were conducted w/HPLC/Coularray detectors (N~600 rats, ~1700 humans). Classification/predictive...

Suboptimal dietary macronutrient choices are arguably the major environmental stressor in individuals living Western societies. Trans and saturated fats contribute to cardio‐ cerebrovascular disease, as do diets high easily digested carbohydrates, which themselves may metabolic syndrome overt diabetes. A massive literature links diet both neoplastic non‐neoplastic diseases, a causal role for mitochondria this relationship is strongly supported by broad areas of inquiry represented...

Excessive caloric intake [CI] and suboptimal dietary macronutrient choices are arguably the major environmental stressor in individuals living Western societies. Unraveling specifics of this inter‐relationship is complicated by well‐known difficulty accurately assessing diet human populations. Our goal thus to discover confirm plasma metabolomic biomarkers for overall [CI]/expenditure, class‐specific fats (eg, saturated, trans), glycemic index, shifts between fats, protein, carbohydrate as...

Calorie Restriction (CR) is the most potent, robust, and reproducible known means of extending longevity decreasing morbidity in a vast range animal species short primates. Despite 80 years research, relevance this observation for humans remains unknown. Relevance supported by established link between obesity humans, health status individuals voluntarily participating caloric restricted lifestyle. Other potential linkages are being directly studied NIA/NIH‐sponsored CALERIE ( C omprehensive...