Obesity is currently epidemic in many countries worldwide and is strongly related to diabetes and cardiovascular disease. This study investigated the differences in metabolomic profiling between overweight/obese and normal-weight men. Overweight/obese (n=30) and age-matched, normal-weight men (n=30) were included. Anthropometric parameters, conventional metabolites, and biomarkers were measured. Metabolomic profiling was analyzed with UPLC-Q-TOF MS. Overweight/obese men showed higher levels of HOMA-IR, triglycerides, total cholesterol, and LDL-cholesterol, and lower levels of HDL-cholesterol and adiponectin than lean men. Overweight/obese men showed higher proportion of stearic acid and lower proportion of oleic acid in serum phospholipids. Additionally, overweight/obese individuals showed higher fat intake and lower ratio of polyunsaturated fatty acids to saturated fatty acids. We identified three lyso-phosphatidylcholine (lysoPC) as potential plasma markers and confirmed eight known metabolites for overweight/obesity men. Especially, overweight/obese subjects showed higher levels of lysoPC C14:0 and lysoPC C18:0 and lower levels of lysoPC C18:1 than lean subjects. Results confirmed abnormal metabolism of two branched-chain amino acids, two aromatic amino acids, and fatty acid synthesis and oxidation in overweight/obese men. Additionally, the amount of dietary saturated fat may influence the proportion of saturated fatty acids in serum phospholipids and the degree of saturation of the constituent acyl group of plasma lysoPC.

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Abstract-Our objective was to evaluate whether isocaloric replacement of refined rice with whole grains and other plant products as a form of powder reduces coronary artery disease (CAD) risk factors, such as insulin demand and lipid peroxidation in CAD patients. Seventy-six male patients with CAD were randomly assigned to either a group ingesting a whole-grain meal daily or a control group for 16 weeks. In the whole-grain group, serum concentrations of glucose and insulin decreased by 24% and 14%, respectively, without altering body weight and energy intake, whereas daily intakes of fiber and vitamin E increased by 25% and 41%, respectively. Consumption of whole grains and legume powder in CAD patients without diabetes decreased fasting levels of glucose and insulin. The areas under the curve for insulin and glucose during the oral glucose tolerance test were also decreased. CAD patients with diabetes in the whole-grain group also showed reductions in fasting glucose and in the area under the curve for glucose. In the whole-grain group, plasma malondialdehyde and homocysteine and urinary 8-epi-prostaglandin F 2␣ concentrations decreased by Ϸ28%. Also, lipid-corrected concentrations of ␣-carotene, retinol, tocopherols, and lycopene increased by 11% to 40%, and the percentage composition of n-6 fatty acids of serum phospholipid increased by 14% in the whole-grain group. The replacement of refined rice with whole grain and legume powder as a source of carbohydrate in a meal showed significant beneficial effects on glucose, insulin, and homocysteine concentrations and lipid peroxidation in CAD patients. These effects are likely to substantially reduce the risk factors for CAD and diabetes.

BackgroundInvasive aspergillosis (IA) is a major cause of infectious morbidity and mortality in immune compromised patients. Studies on the pathogenesis of IA have been limited by the difficulty to monitor disease progression in real-time. For real-time monitoring of the infection, we recently engineered a bioluminescent A. fumigatus strain.ResultsIn this study, we demonstrate that bioluminescence imaging can track the progression of IA at different anatomic locations in a murine model of disease that recapitulates the natural route of infection. To define the temporal and functional requirements of distinct innate immune cellular subsets in host defense against respiratory A. fumigatus infection, we examined the development and progression of IA using bioluminescence imaging and histopathologic analysis in mice with four different types of pharmacologic or numeric defects in innate immune function that target resident and recruited phagocyte subsets. While bioluminescence imaging can track the progression and location of invasive disease in vivo, signals can be attenuated by severe inflammation and associated tissue hypoxia. However, especially under non-inflammatory conditions, such as cyclophosphamide treatment, an increasing bioluminescence signal reflects the increasing biomass of alive fungal cells.ConclusionsImaging studies allowed an in vivo correlation between the onset, peak, and kinetics of hyphal tissue invasion from the lung under conditions of functional or numeric inactivation of phagocytes and sheds light on the germination speed of conidia under the different immunosuppression regimens. Conditions of high inflammation -either mediated by neutrophil influx under corticosteroid treatment or by monocytes recruited during antibody-mediated depletion of neutrophils- were associated with rapid conidial germination and caused an early rise in bioluminescence post-infection. In contrast, 80% alveolar macrophage depletion failed to trigger a bioluminescent signal, consistent with the notion that neutrophil recruitment is essential for early host defense, while alveolar macrophage depletion can be functionally compensated.

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SummaryObjective To determine whether circulating metabolic intermediates are associated with inflammation, oxidative stress and arterial stiffness in men with newly diagnosed type 2 diabetes and investigate the circulating metabolic intermediates that may predict the risk of developing diabetes. Research design and methods Men with newly diagnosed type 2 diabetes (n = 26) and age-and body mass index-matched nondiabetic men (n = 27) were included. We measured inflammatory and oxidative markers and arterial stiffness by brachial-ankle pulse wave velocity (ba-PWV). Metabolomic profiling was analysed with ultra performance liquid chromatography and quadrupole timeof-flight mass spectrometry. Results Diabetic men showed higher circulating levels of glucose, triglyceride, oxidized low-density lipoprotein (LDL), high-sensitivity C-reactive protein, interleukin (IL)-6, tumour necrosis factoralpha (TNF-a), homeostasis model assessment-insulin resistance, urinary 8-epi-prostaglandin F 2a (8-epi-PGF 2a ) and ba-PWV than nondiabetic men. In plasma, 19 metabolites including three amino acids, eight acylcarnitines, six lysophosphatidylcholines (lysoPCs), and two lysophosphatidylethanolamines (lysoPEs; C18:2 and C22:6) significantly increased in diabetes men, whereas serine and lysoPE (C18:1) decreased. Decanoyl carnitine, lysoPCs (C14:0, C16:1, C18:1 and C22:6) and lysoPE (C18:1) with variable importance in the projection values >1AE0 were major plasma metabolites that distinguished nondiabetic and diabetic men. Decanoyl carnitine positively correlated with oxidized LDL, 8-epi-PGF 2a , IL-6, TNF-a and ba-PWV. ba-PWV correlated positively with lysoPCs C14:0 and C16:1, and negatively with lysoPE C18:1. 8-epi-PGF 2a correlated positively with lipoprotein-associated phospholipase A 2 , ba-PWV and lysoPCs (C14:0 and C16:1). The receiver operating characteristic curve estimation suggested that decanoyl carnitine and lysoPC (C14:0) are the best metabolites for predicting the risk of developing diabetes. Conclusions Circulating lipid-related intermediate metabolites can be closely associated with inflammation, oxidative stress and arterial stiffness in early diabetes.