Lipid metabolism in dendritic cell biology.

Dendritic cells (DCs) are innate immune cells that detect and process environmental signals and communicate them with T cells to bridge innate and adaptive immunity. Immune signals and microenvironmental cues shape the function of DC subsets in different contexts, which is associated with reprogramming of cellular metabolic pathways. In addition to integrating these extracellular cues to meet bioenergetic and biosynthetic demands, cellular metabolism interplays with immune signaling to shape DC-dependent immune responses. Emerging evidence indicates that lipid metabolism serves as a key regulator of DC responses. Here, we summarize the roles of fatty acid and cholesterol metabolism, as well as selective metabolites, in orchestrating the functions of DCs. Specifically, we highlight how different lipid metabolic programs, including de novo fatty acid synthesis, fatty acid ß oxidation, lipid storage, and cholesterol efflux, influence DC function in different contexts. Further, we discuss how dysregulation of lipid metabolism shapes DC intracellular signaling and contributes to the impaired DC function in the tumor microenvironment. Finally, we conclude with a discussion on key future directions for the regulation of DC biology by lipid metabolism. Insights into the connections between lipid metabolism and DC functional specialization may facilitate the development of new therapeutic strategies for human diseases.

Mendelian randomization analysis reveals causal effects of blood lipidome on gestational diabetes mellitus.

BACKGROUND: Observational studies have revealed associations between maternal lipid metabolites and gestational diabetes mellitus (GDM). However, whether these associations are causal remain uncertain. OBJECTIVE: To evaluate the causal relationship between lipid metabolites and GDM. METHODS: A two-sample Mendelian randomization (MR) analysis was performed based on summary statistics. Sensitivity analyses, validation analyses and reverse MR analyses were conducted to assess the robustness of the MR results. Additionally, a phenome-wide MR (Phe-MR) analysis was performed to evaluate potential side effects of the targeted lipid metabolites. RESULTS: A total of 295 lipid metabolites were included in this study, 29 of them had three or more instrumental variables (IVs) suitable for sensitivity analyses. The ratio of triglycerides to phosphoglycerides (TG_by_PG) was identified as a potential causal biomarker for GDM (inverse variance weighted (IVW) estimate: odds ratio (OR) = 2.147, 95% confidential interval (95% CI) 1.415-3.257, P = 3.26e-4), which was confirmed by validation and reverse MR results. Two other lipid metabolites, palmitoyl sphingomyelin (d18:1/16:0) (PSM(d18:1/16:0)) (IVW estimate: OR = 0.747, 95% CI 0.583-0.956, P = 0.021) and triglycerides in very small very low-density lipoprotein (XS_VLDL_TG) (IVW estimate: OR = 2.948, 95% CI 1.197-5.215, P = 0.015), were identified as suggestive potential biomarkers for GDM using a conventional cut-off P-value of 0.05. Phe-MR results indicated that lowering TG_by_PG had detrimental effects on two diseases but advantageous effects on the other 13 diseases. CONCLUSION: Genetically predicted elevated TG_by_PG are causally associated with an increased risk of GDM. Side-effect profiles indicate that TG_by_PG might be a target for GDM prevention, though caution is advised due to potential adverse effects on other conditions.

Identification of three potential novel biomarkers for early diagnosis of acute ischemic stroke via plasma lipidomics.

INTRODUCTION: Acute ischemic stroke (AIS) accounts for the majority of all stroke, globally the second leading cause of death. Due to its rapid development after onset, its early diagnosis is crucial. OBJECTIVES: We aim to identify potential highly reliable blood-based biomarkers for early diagnosis of AIS using quantitative plasma lipid profiling via a machine learning approach. METHODS: Lipidomics was used for quantitative plasma lipid profiling, based on ultra-performance liquid chromatography tandem mass spectrometry. Our samples were divided into a discovery and a validation set, each containing 30 AIS patients and 30 health controls (HC). Differentially expressed lipid metabolites were screened based on the criteria VIP > 1, p < 0.05, and fold change > 1.5 or < 0.67. The least absolute shrinkage and selection operator (LASSO) and random forest algorithms in machine learning were used to select differential lipid metabolites as potential biomarkers. RESULTS: Three key differential lipid metabolites, CarnitineC10:1, CarnitineC10:1-OH and Cer(d18:0/16:0), were identified as potential biomarkers for early diagnosis of AIS. The former two, associated with thermogenesis, were down-regulated, whereas the latter, associated with necroptosis and sphingolipd metabolism, was upregulated. Univariate and multivariate logistic regressions showed that these three lipid metabolites and the resulting diagnostic model exhibited a strong ability in discriminating between AIS patients and HCs in both the discovery and validation sets, with an area under the curve above 0.9. CONCLUSIONS: Our work provides valuable information on the pathophysiology of AIS and constitutes an important step toward clinical application of blood-based biomarkers for diagnosing AIS.

Comprehensive analysis of lipid metabolism in influenza virus infection.

Influenza A virus (IAV) exploits host metabolic pathways to support its replication. To improve the understanding of lipid metabolic changes that could occur upon IAV infection, a comprehensive analysis of lipid metabolites in A549 cells infected with the avian H9N2 virus at the different time points was performed. It was found that H9N2 infection could largely promote the level of lipid metabolites. Further, these metabolites were mainly included in glycerophospholipids (GPs), sphingolipids (SPs), glycerolipids (GLs), fatty acids (FAs), sterollipids (STs), triglycerides (TGs), and prenol lipids (PRs). Specifically, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these metabolites were mainly associated with the glycerphospholipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, and autophagy. Furthermore, it is interesting to note that these metabolites, including FFA(19:1), PE(P-17:0_20:3), PE(P-18:1_20:2), LPC(14:0/0:0), PE(O-18:0_20:3), and MGDG(16:0_18:1), are upregulated and shared in the top 10 at 12 h, 24 h, 36 h, and 48 h after H9N2 infection, indicative of the possibility of acting as biomarkers for the diagnosis in the lung infected with influenza virus. These pathways and altered metabolites could provide new understandings about biological characteristics and pathogenicity of influenza virus and have the potential to serve as biomarkers for influenza.

Cadmium influence on lipid metabolism in Sprague-Dawley rats through linoleic acid and glycerophospholipid metabolism pathways.

Cadmium (Cd) is widely distributed in the environment and easy adsorbed by living organisms with adverse effects. Exposure to Cd-contaminated food may disrupt lipid metabolism and increase human health risk. To study the perturbation effect of Cd on lipid metabolism in vivo, 24 male Sprague-Dawley (SD) rats were randomly assigned four groups and treated by Cd chloride solution (0, 1.375 mg/kg, 5.5 mg/kg, 22 mg/kg) for 14 days. The characteristic indexes of serum lipid metabolism were analyzed. Afterwards, untargeted metabolomics analysis was applied to explore the adverse effects of Cd on rats by liquid chromatography coupled with mass spectrometry (LC-MS). The results revealed that Cd exposure obviously decreased the average serum of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and caused an imbalance of endogenous compounds in the 22 mg/kg Cd-exposed group. Compared with the control group, 30 metabolites with significant differences were identified in the serum. Our results indicated that Cd caused lipid metabolic disorders in rats by disrupting linoleic acid and glycerophospholipid metabolism pathways. Furthermore, there were three kinds of remarkable differential metabolites-9Z,12Z-octadecadienoic acid, PC(20:4(8Z,11Z,14Z,17Z)/0:0), and PC(15:0/18:2(9Z,12Z)), which enriched the two significant metabolism pathways and could be the potential biomarkers.

The Sizes and Composition of HDL-Cholesterol Are Significantly Associated with Inflammation in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA), a chronic inflammatory disease, carries a significant burden of atherosclerotic cardiovascular diseases (ASCVD). With their heterogeneous composition, high-density lipoprotein (HDL) particles have varied athero-protective properties, and some may even increase ASCVD risk. In this prospective and cross-sectional study, we aimed to examine the relationship between HDL sizes/metabolites and inflammation in RA. Using 1H-NMR-based lipid/metabolomics, differential HDL-related metabolites were identified between RA patients and healthy control (HC) subjects and between RA patients with and without anti-citrullinated peptide antibodies (ACPA). The correlation between the discriminative HDL-related metabolites and C-reactive protein (CRP) was evaluated in RA patients. RA patients demonstrated higher particle number, lipids, cholesterol, cholesterol ester, free cholesterol, and phospholipids in large/very large-sized HDLs. ACPA-positive patients had higher L-HDL-C and L-HDL-CE but lower small-/medium-sized HDL-TG levels than ACPA-negative patients. An inverse correlation was found between CRP levels and small-sized HDLs. Janus kinase inhibitor treatment was associated with increased serum small-sized HDL-related metabolites and decreased CRP levels. We are the first to reveal the significant associations between RA inflammation and HDL sizes/metabolites. A potential link between ACPA positivity and changes in serum levels of HDL-related metabolites was also observed in RA patients.

Acute Stress-Induced Changes in the Lipid Composition of Cow's Milk in Healthy and Pathological Animals.

Producers of milk and dairy products have been faced with the challenge of responding to European society's demand for guaranteed animal welfare production. In recent years, measures have been taken to improve animal welfare conditions on farms and evaluation systems have been developed to certify them, such as the Welfare Quality® protocol. Among the markers used for this purpose, acute phase proteins stand out, with haptoglobin being one of the most relevant. However, the diagnostic power of these tools is limited and more sensitive and specific technologies are required to monitor animal health status. Different factors such as diet, stress, and diseases modify the metabolism of the animals, altering the composition of the milk in terms of oligosaccharides, proteins, and lipids. Thus, in order to study oxidative-stress-associated lipids, a collection of well-characterized milk samples, both by veterinary diagnosis and by content of the acute stress biomarker haptoglobin, was analyzed by mass spectrometry and artificial intelligence. Two lipid species (sphingomyelin and phosphatidylcholine) were identified as potential biomarkers of health status in dairy cows. Both lipids allow for the discrimination of milk from sick animals and also milk from those with stress. Moreover, lipidomics revealed specific lipid profiles depending on the origin of the samples and the degree of freedom of the animals on the farm. These data provide evidence for specific lipid changes in stressed animals and open up the possibility that haptoglobin could also affect lipid metabolism in cow's milk.

Gut Microbiota Mediates Skin Ulceration Syndrome Outbreak by Readjusting Lipid Metabolism in Apostichopus japonicus.

The intestinal tract is the most important location for symbiotes and pathogens, and the microbiota plays a crucial role in affecting the health of the gut and other host organs. Dysbacteriosis in the intestinal system has been proven to be significant in skin ulceration syndrome (SUS) in sea cucumbers. This study investigates whether the gut microbiota and lipid metabolites are relevant to the initiation and progression of SUS in a Vibrio-splendidus-infected sea cucumber model. The tight junction genes were downregulated and the inflammatory factor gene transcriptions were upregulated after V. splendidus infection in the intestinal tissue of the sea cucumber. V. splendidus infection modulated the gut microbiota by interacting with Psychromonas macrocephali, Propionigenium maris, Bacillus cereus, Lutibacter flavus, and Hoeflea halophila. Meanwhile, the metabolites of the long-chain fatty acids in the intestinal tissue, including triglycerides (TG), phosphatidylethanolamines (PE), and phosphatidylglycerols (PG), were altered after V. splendidus infection. V. splendidus engaged in positive interactions with PG and PE and negative interactions with specific TG. These results related to gut microbiota and metabolites can offer practical assistance in the identification of the inflammatory mechanisms related to SUS, and this study may serve as a reference for predicting the disease.

Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes.

AIMS/HYPOTHESIS: Emerging evidence suggests that in addition to hyperglycaemia, dyslipidaemia could represent a contributing pathogenetic factor to diabetic neuropathy, while obesity and insulin resistance play a role in the development of diabetic cardiac autonomic neuropathy (CAN) characterised by reduced heart rate variability (HRV), particularly in type 2 diabetes. We hypothesised that distinct lipid metabolites are associated with diminished HRV in recent-onset type 2 diabetes rather than type 1 diabetes. METHODS: We analysed 127 plasma lipid metabolites (11 acylcarnitines, 39 NEFA, 12 sphingomyelins (SMs), 56 phosphatidylcholines and nine lysophosphatidylcholines) using MS in participants from the German Diabetes Study baseline cohort recently diagnosed with type 1 (n = 100) and type 2 diabetes (n = 206). Four time-domain HRV indices (number of normal-to-normal (NN) intervals >50 ms divided by the number of all NN intervals [pNN50]; root mean square of successive differences [RMSSD]; SD of NN intervals [SDNN]; and SD of differences between adjacent NN intervals) and three frequency-domain HRV indices (very-low-frequency [VLF], low-frequency [LF] and high-frequency [HF] power spectrum) were computed from NN intervals recorded during a 3 h hyperinsulinaemic-euglycaemic clamp at baseline and in subsets of participants with type 1 (n = 60) and type 2 diabetes (n = 95) after 5 years. RESULTS: In participants with type 2 diabetes, after Bonferroni correction and rigorous adjustment, SDNN was inversely associated with higher levels of diacyl-phosphatidylcholine (PCaa) C32:0, PCaa C34:1, acyl-alkyl-phosphatidylcholine (PCae) C36:0, SM C16:0 and SM C16:1. SD of differences between NN intervals was inversely associated with PCaa C32:0, PCaa C34:1, PCaa C34:2, PCae C36:0 and SM C16:1, and RMSSD with PCae C36:0. For VLF power, inverse associations were found with PCaa C30:0, PCaa C32:0, PCaa C32:1, PCaa C34:2 and SM C16:1, and for LF power inverse associations were found with PCaa C32:0 and SM C16:1 (r = -0.242 to r = -0.349; p ≤ 0.0005 for all correlations). In contrast, no associations of lipid metabolites with measures of cardiac autonomic function were noted in participants recently diagnosed with type 1 diabetes. After 5 years, HRV declined due to ageing rather than diabetes, whereby prediction analyses for lipid metabolites were hampered. CONCLUSIONS/INTERPRETATION: Higher plasma levels of specific lipid metabolites are closely linked to cardiac autonomic dysfunction in recent-onset type 2 diabetes but not type 1 diabetes, suggesting a role for perturbed lipid metabolism in the early development of CAN in type 2 diabetes. Graphical abstract.

Cardiac-specific VEGFB overexpression reduces lipoprotein lipase activity and improves insulin action in rat heart.

Cardiac muscle uses multiple sources of energy including glucose and fatty acid (FA). The heart cannot synthesize FA and relies on obtaining it from other sources, with lipoprotein lipase (LPL) breakdown of lipoproteins suggested to be a key source of FA for cardiac use. Recent work has indicated that cardiac vascular endothelial growth factor B (VEGFB) overexpression expands the coronary vasculature and facilitates metabolic reprogramming that favors glucose utilization. We wanted to explore whether this influence of VEGFB on cardiac metabolism involves regulation of LPL activity with consequent effects on lipotoxicity and insulin signaling. The transcriptomes of rats with and without cardiomyocyte-specific overexpression of human VEGFB were compared by using RNA sequencing. Isolated perfused hearts or cardiomyocytes incubated with heparin were used to enable measurement of LPL activity. Untargeted metabolomic analysis was performed for quantification of cardiac lipid metabolites. Cardiac insulin sensitivity was evaluated using fast-acting insulin. Isolated heart and cardiomyocytes were used to determine transgene-encoded VEGFB isoform secretion patterns and mitochondrial oxidative capacity using high-resolution respirometry and extracellular flux analysis. In vitro, transgenic cardiomyocytes incubated overnight and thus exposed to abundantly secreted VEGFB isoforms, in the absence of any in vivo confounding regulators of cardiac metabolism, demonstrated higher basal oxygen consumption. In the whole heart, VEGFB overexpression induced an angiogenic response that was accompanied by limited cardiac LPL activity through multiple mechanisms. This was associated with a lowered accumulation of lipid intermediates, diacylglycerols and lysophosphatidylcholine, that are known to influence insulin action. In response to exogenous insulin, transgenic hearts demonstrated increased insulin sensitivity. In conclusion, the interrogation of VEGFB function on cardiac metabolism uncovered an intriguing and previously unappreciated effect to lower LPL activity and prevent lipid metabolite accumulation to improve insulin action. VEGFB could be a potential cardioprotective therapy to treat metabolic disorders, for example, diabetes.NEW & NOTEWORTHY In hearts overexpressing vascular endothelial growth factor B (VEGFB), besides its known angiogenic response, multiple regulatory mechanisms lowered coronary LPL. This was accompanied by limited cardiac lipid metabolite accumulation with an augmentation of cardiac insulin action. Our data for the first time links VEGFB to coronary LPL in regulation of cardiac metabolism. VEGFB may be cardioprotective in metabolic disorders like diabetes.

Physiological markers suggest energetic and nutritional adjustments in male sharks linked to reproduction.

Energetic condition is one of the most important factors that influence fitness and reproductive performance in vertebrates. Yet, we lack evidence on how energetic states change in response to reproduction in large marine vertebrates. In the present study, we used a non-lethal approach to assess relationships among reproductive stage, circulating steroid hormones (testosterone and relative corticosteroid levels), plasma fatty acids, and the ketone body ß-hydroxybutyrate in male sharks of two species with divergent ecologies, the benthic nurse shark (Ginglymostoma cirratum) and the epipelagic blacktip shark (Carcharhinus limbatus). We found higher relative corticosteroid levels in adult nurse sharks during the pre-mating period and in blacktip sharks during the mating period. Higher levels of ß-hydroxybutyrate were found in adult nurse sharks during the mating period, but concentrations of this ketone body did not significantly vary across reproductive stages in blacktip sharks. We also detected reduced percentages of essential fatty acids during the mating period of both nurse and blacktip sharks. Taken together, our findings suggest that nurse and blacktip sharks differ in their energetic strategy to support reproduction, however, they likely rely on physiologically important fatty acids during mating, to support spermatogenesis.

Emerging roles of metabolites of ω3 and ω6 essential fatty acids in the control of intestinal inflammation.

The gastrointestinal tract is continuously exposed to the external environment, which contains numerous non-self antigens, including food materials and commensal micro-organisms. For the maintenance of mucosal homeostasis, the intestinal epithelial layer and mucosal immune system simultaneously provide the first line of defense against pathogens and are tightly regulated to prevent their induction of inflammatory responses to non-pathogenic antigens. Defects in mucosal homeostasis lead to the development of inflammatory and associated intestinal diseases, such as Crohn's disease, ulcerative colitis, food allergy and colorectal cancer. The recent discovery of novel dietary ω3 and ω6 lipid-derived metabolites-such as resolvin, protectin, maresin, 17,18-epoxy-eicosatetraenoic acid and microbe-dependent 10-hydroxy-cis-12-octadecenoic acid-and their potent biologic effects on the regulation of inflammation have initiated a new era of nutritional immunology. In this review, we update our understanding of the role of lipid metabolites in intestinal inflammation.

Nutritional Lipidomics in Alzheimer's Disease.

Lipids constitute almost 60% of the brain's dry weight, and they are thought to be involved in inflammation, neurotransmission and synaptic plasticity. The brain mostly contains sphingolipids, glycerophospholipids and cholesterol which are abundant in myelin and neuronal membranes. The recent rise of the promising area of lipidomic data can be used as a diagnosing tool at the early stages of Alzheimer's disease allowing novel therapeutic targets. In this review, altered lipid metabolites as well as the impact of diet in the progress of Alzheimer's disease (AD) are analyzed.

Adipocytes in the Tumour Microenvironment.

Adipose tissue contribution to body mass ranges from 6% in male athletes to over 25% in obese men and over 30% in obese women. Crosstalk between adipocytes and cancer cells that exist in close proximity can lead to changes in the function and phenotype of both cell types. These interactions actively alter the tumour microenvironment (TME). Obesity is one of the major risk factors for multiple types of cancer, including breast cancer. In obesity, the increase in both size and number of adipocytes leads to instability of the TME, as well as increased hypoxia within the TME, which further enhances tumour invasion and metastasis. In this chapter, we will discuss the diverse aspects of adipocytes and adipocyte-derived factors that affect the TME as well as tumour progression and metastasis. In addition, we discuss how obesity affects the TME. We focus primarily on breast cancer but discuss what is known in other cancer types when relevant. We finish by discussing the studies needed to further understand these complex interactions.

Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization.

Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A growing body of evidence supports a strong link between neovascular disease and inflammation. Metabolites of long-chain polyunsaturated fatty acids derived from the cytochrome P450 (CYP) monooxygenase pathway serve as vital second messengers that regulate a number of hormones and growth factors involved in inflammation and vascular function. Using transgenic mice with altered CYP lipid biosynthetic pathways in a mouse model of laser-induced CNV, we characterized the role of these lipid metabolites in regulating neovascular disease. We discovered that the CYP-derived lipid metabolites epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs) are vital in dampening CNV severity. Specifically, overexpression of the monooxygenase CYP2C8 or genetic ablation or inhibition of the soluble epoxide hydrolase (sEH) enzyme led to increased levels of EDP and EEQ with attenuated CNV development. In contrast, when we promoted the degradation of these CYP-derived metabolites by transgenic overexpression of sEH, the protective effect against CNV was lost. We found that these molecules work in part through their ability to regulate the expression of key leukocyte adhesion molecules, on both leukocytes and endothelial cells, thereby mediating leukocyte recruitment. These results suggest that CYP lipid signaling molecules and their regulators are potential therapeutic targets in neovascular diseases.

Are Alterations in Skeletal Muscle Mitochondria a Cause or Consequence of Insulin Resistance?

As a major site of glucose uptake following a meal, skeletal muscle has an important role in whole-body glucose metabolism. Evidence in humans and animal models of insulin resistance and type 2 diabetes suggests that alterations in mitochondrial characteristics accompany the development of skeletal muscle insulin resistance. However, it is unclear whether changes in mitochondrial content, respiratory function, or substrate oxidation are central to the development of insulin resistance or occur in response to insulin resistance. Thus, this review will aim to evaluate the apparent conflicting information placing mitochondria as a key organelle in the development of insulin resistance in skeletal muscle.

Identification of Plasma Lipid Metabolites Associated with Nut Consumption in US Men and Women.

BACKGROUND: Intake of nuts has been inversely associated with risk of type 2 diabetes and cardiovascular disease, partly through inducing a healthy lipid profile. How nut intake may affect lipid metabolites remains unclear. OBJECTIVE: The aim of this study was to identify the plasma lipid metabolites associated with habitual nut consumption in US men and women. METHODS: We analyzed cross-sectional data from 1099 participants in the Nurses' Health Study (NHS), NHS II, and Health Professionals Follow-up Study. Metabolic profiling was conducted on plasma by LC-mass spectrometry. Nut intake was estimated from food-frequency questionnaires. We included 144 known lipid metabolites that had CVs ≤25%. Multivariate linear regression was used to assess the associations of nut consumption with individual plasma lipid metabolites. RESULTS: We identified 17 lipid metabolites that were significantly associated with nut intake, based on a 1 serving (28 g)/d increment in multivariate models [false discovery rate (FDR) P value <0.05]. Among these species, 8 were positively associated with nut intake [C24:0 sphingomyelin (SM), C36:3 phosphatidylcholine (PC) plasmalogen-A, C36:2 PC plasmalogen, C24:0 ceramide, C36:1 PC plasmalogen, C22:0 SM, C34:1 PC plasmalogen, and C36:2 phosphatidylethanolamine plasmalogen], with changes in relative metabolite level (expressed in number of SDs on the log scale) ranging from 0.36 to 0.46 for 1 serving/d of nuts. The other 9 metabolites were inversely associated with nut intake with changes in relative metabolite level ranging from -0.34 to -0.44. In stratified analysis, 3 metabolites were positively associated with both peanuts and peanut butter (C24:0 SM, C24:0 ceramide, and C22:0 SM), whereas 6 metabolites were inversely associated with other nuts (FDR P value <0.05). CONCLUSIONS: A panel of lipid metabolites was associated with intake of nuts, which may provide insight into biological mechanisms underlying associations between nuts and cardiometabolic health. Metabolites that were positively associated with intake of nuts may be helpful in identifying potential biomarkers of nut intake.

Proton MR spectroscopy in the breast: Technical innovations and clinical applications.

Proton magnetic resonance spectroscopy (MRS) is a promising noninvasive diagnostic technique for investigation of breast cancer metabolism. Spectroscopic imaging data may be obtained following contrast-enhanced MRI by applying the point-resolved spectroscopy sequence (PRESS) or the stimulated echo acquisition mode (STEAM) sequence from the MR voxel encompassing the breast lesion. Total choline signal (tCho) measured in vivo using either a qualitative or quantitative approach has been used as a diagnostic test in the workup of malignant breast lesions. In addition to tCho metabolites, other relevant metabolites, including multiple lipids, can be detected and monitored. MRS has been heavily investigated as an adjunct to morphologic and dynamic MRI to improve diagnostic accuracy in breast cancer, obviating unnecessary benign biopsies. Besides its use in the staging of breast cancer, other promising applications have been recently investigated, including the assessment of treatment response and therapy monitoring. This review provides guidance on spectroscopic acquisition and quantification methods and highlights current and evolving clinical applications of proton MRS. Level of Evidence 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.

Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites.

AIMS: Epidemiological studies have correlated cardiovascular disease and atherosclerosis with lifestyle factors such as sedentary behaviour and a high-calorie diet. Recent studies of pathogenesis have highlighted the significance of the intestinal microbiota and chronic inflammation with respect to both the onset and development of atherosclerosis. This study examined the hypothesis that the oral administration of quercetin to low-density lipoprotein receptor-null (Ldlr-/- ) mice would improve gut health by altering the gut microbiota and controlling the levels of atherogenic lipid metabolites and proinflammatory mediators in the intestine and serum. METHODS AND RESULTS: Mice were maintained on a high-fat diet with or without oral quercetin administration for 12 weeks. Quercetin treatment suppressed body weight gains and reduced the extent of atherosclerotic lesions in the aortic sinus. Reduced malondialdehyde and increased interleukin 6 levels further indicated the protective effect of quercetin against immune/inflammatory responses and oxidative stress. Furthermore, quercetin led to decreased intestinal levels of cholesterol, lysophosphatidic acids and atherogenic lysophosphatidylcholine (LPC 18:1) and an increased level of coprostanol. A phylum-level microbial analysis revealed that quercetin treatment reduced the abundance of Verrocomicrobia and increased microbiome diversity and the abundances of Actinobacteria, Cyanobacteria and Firmicutes. A Spearman analysis revealed negative correlations of Actinobacteria with intestinal and plasma LPC 18:1 and caecal cholesterol levels and of Firmicutes and Cyanobacteria with the plasma LPC 18:1 level. CONCLUSIONS: This study demonstrated the ability of quercetin treatment to reduce lipid levels, as well as the areas of atherosclerotic lesions and sizes of plaques. This treatment also altered the composition of the gut microbiota and decreased the levels of atherogenic lipid metabolites. SIGNIFICANCE AND IMPACT OF THE STUDY: Oral quercetin treatment may represent a new approach to mitigating the onset and development of atherosclerosis.

Influence of feeding a fish oil-containing diet to mature, overweight dogs: Effects on lipid metabolites, postprandial glycaemia and body weight.

The objective of this study was to determine the effect of feeding a fish oil (FO)-containing diet on lipid and protein metabolism, postprandial glycaemia and body weight (BW) of mature, overweight dogs. Seven female dogs were randomly assigned to one of two isonitrogenous and isocaloric diets, control (CO) or FO (FO), in a crossover design. Experimental periods were 69 day, separated by a washout period of 30 day. At the beginning of the experiment, and at 30 and 60 day of feeding the experimental diets, the dogs were infused with D-glucose (2 g/kg BW) through an intravenous catheter. Blood samples were collected for 3 hr to perform a glucose tolerance test. Nitrogen balance measurements began at 06:30 on d 63 of each experimental period and ended at 06:30 on d 69. On d 66 of each period, a single dose (7.5 mg/kg) of 15 N-glycine was administered orally for determination of protein turnover. Incremental area under the curve and glucose concentration at peak did not differ between treatments or among sampling days within treatment. Glucose half-life tended to decrease (p < .10) in the FO treatment on day 30 when compared to baseline (day 0). ß-hydroxybutyrate, non-esterified fatty acid (NEFA) and triglycerides did not differ within or between treatments. Cholesterol decreased (p < .05) on the FO treatment on day 30, 60 and 69 when compared to day 0. High-density lipoprotein (HDL) decreased (p < .05) in the FO treatment on day 69 when compared to day 0. Body weight, food intake, faecal excretion, DM and N digestibilities, N balance and protein turnover were not different between diets. Overall, FO-containing diet decreases cholesterol in mature overweight dogs; however, further research is warranted to verify the effects of FO on glucose metabolism.