Project description:Chemoautotrophic bacteria from the SUP05 clade often dominate anoxic waters in marine oxygen minimum zones (OMZs) where reduced sulfur can fuel carbon fixation and denitrification. Some members of the SUP05 clade are facultative aerobes that thrive at the boundaries of OMZs where they experience fluctuations in dissolved oxygen (DO). The degree to which SUP05 contribute to nitrate reduction in these regions depends on their sensitivity to oxygen. We evaluated growth and quantified differences in gene expression in Ca. T. autotrophicus strain EF1 from the SUP05 clade under high DO (22 μM), anoxic, and low DO (3.8 μM) concentrations. We show that strain EF1 cells respire oxygen and nitrate and that cells have higher growth rates, express more genes, and fix more carbon when oxygen becomes available for aerobic respiration. Evidence that facultatively aerobic SUP05 are more active and respire nitrate when oxygen becomes available at low concentrations suggests that they are an important source of nitrite across marine OMZ boundary layers.
Project description:Neutrophils play a key role in the control of metastatic progression. Neutrophils are phenotypically heterogeneous and can exert either anti- or pro-metastatic functions. Here, we demonstrate that tumor cells capable of forming liver metastases induce an accumulation of neutrophils in the peripheral blood and liver parenchyma. Cancer cell-derived G-CSF, in concert with other factors, mobilizes immature low-density neutrophils that promote liver metastasis. In contrast, mature high-density neutrophils inhibit the formation of liver metastases. Transcriptomic and metabolomic analyses of high- and low- density neutrophils reveal engagement of numerous metabolic pathways specifically in low-density neutrophils. Low-density neutrophils exhibit enhanced global bioenergetic capacity, through their ability to engage mitochondrial-dependent ATP production, and remain capable of executing pro-metastatic neutrophil functions, including NETosis, under nutrient-deprived conditions. Together, these data reveal that distinct pro-metastatic neutrophil populations exhibit a high degree of metabolic flexibility, which facilitates metastatic progression and the formation of liver metastases.
Project description:This SuperSeries is composed of the following subset Series: GSE36716: Muscle Involvement in Preservation of Metabolic Flexibility by Treatment using n-3 PUFA or Rosiglitazone in Dietary-Obese Mice GSE36717: Muscle Involvement in Preservation of Metabolic Flexibility by a Combination Treatment using n-3 PUFA and Rosiglitazone in Dietary-Obese Mice Refer to individual Series
Project description:Bezafibrate (BEZ), a pan activator of peroxisome proliferator-activated receptors (PPARs), is generally used to treat hyperlipidemia. Clinical trials on patients suffering from type 2 diabetes indicated that BEZ also has beneficial effects on glucose metabolism, but the underlying mechanisms remain elusive. Much less is known about the function of BEZ in type 1 diabetes. Here, we show that BEZ treatment markedly improves hyperglycemia, glucose and insulin tolerance in streptozotocin (STZ)-treated mice, an insulin-deficient mouse model of type 1 diabetes presenting with very high blood glucose levels. Furthermore, BEZ-treated mice also exhibited improved metabolic flexibility as well as an enhanced mitochondrial mass and function in the liver. Our data demonstrate a beneficial effect of BEZ treatment on STZ mice reducing diabetes and suggest that BEZ ameliorates impaired glucose metabolism possibly via augmented hepatic mitochondrial performance, improved insulin sensitivity and metabolic flexibility. We performed gene expression microarray analysis on liver tissue derived from streptozotocin-treated mice treated with bezafibrate in addition.
Project description:Bezafibrate (BEZ), a pan activator of peroxisome proliferator-activated receptors (PPARs), is generally used to treat hyperlipidemia. Clinical trials on patients suffering from type 2 diabetes indicated that BEZ also has beneficial effects on glucose metabolism, but the underlying mechanisms remain elusive. Much less is known about the function of BEZ in type 1 diabetes. Here, we show that BEZ treatment markedly improves hyperglycemia, glucose and insulin tolerance in streptozotocin (STZ)-treated mice, an insulin-deficient mouse model of type 1 diabetes presenting with very high blood glucose levels. Furthermore, BEZ-treated mice also exhibited improved metabolic flexibility as well as an enhanced mitochondrial mass and function in the liver. Our data demonstrate a beneficial effect of BEZ treatment on STZ mice reducing diabetes and suggest that BEZ ameliorates impaired glucose metabolism possibly via augmented hepatic mitochondrial performance, improved insulin sensitivity and metabolic flexibility.
Project description:Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme regulating cellular energy metabolism across all species. Recent studies have shown the pleiotropic roles of adipose tissue NAD+ biology in adipose tissue and whole-body metabolism. The major purpose of the present study was to test the hypothesis that adipose tissue NAD+ biosynthesis, mediated by nicotinamide phosphoribosyltransferase (NAMPT), is a physiological regulator of whole-body metabolic flexibility. To this end, we analyzed adipocyte-specific Nampt knockout (ANKO) mice and subcutaneous white adipose tissue (WAT) biopsy samples obtained from human subjects. We found ANKO mice preferably utilized glucose substrate during the light period or after prolonged fasting. In contrast, ANKO mice had marked decreases in stimulation of glucose oxidation and suppression of fat oxidation during the postprandial status despite hyperinsulinemia. Data obtained from RNA-sequencing of WAT suggest that loss of NAMPT causes inflammation, oxidative stress, defective fatty acid oxidation, and mitochondrial dysfunction in WAT, key features of obesity and metabolic inflexibility. We also found WAT NAD+ concentration was decreased in people with obesity and insulin resistance compared with those who were non-obese and insulin-sensitive. In addition, bariatric surgery-induced 20% weight loss increased WAT NAD+ concentration in people with obesity. Taken together, our results reveal the importance of adipose tissue NAMPT-mediated NAD+ biosynthesis in regulating whole-body metabolic flexibility. Our results also provide translational and clinical insight into adipose tissue NAD+ biology in obesity and whole-body metabolic health.