Regulation of cardiolipin biosynthesis by fatty acid transport protein-1 IN HEK 293 cells

AbstractCardiolipin (CL) is a major phospholipid involved in energy metabolism mammalian mitochondria and fatty acid transport protein-1 (FATP-1) is a fatty acid transport protein that may regulate the intracellular level of fatty acyl-Coenzyme A's. Since fatty acids are required for oxidative phosphorylation via mitochondrial oxidation, we examined the effect of altering FATP-1 levels on CL biosynthesis. HEK-293 mock- and FATP-1 siRNA transfected cells or mock and FATP-1 expressing cells were incubated for 24 h with 0.1 mM oleic acid bound to albumin (1:1 molar ratio) then incubated for 24 h with 0.1 mM [1,3-3H]glycerol and radioactivity incorporated into CL determined. FATP-1 siRNA transfected cells exhibited reduced FATP-1 mRNA and increased incorporation of [1,3-3H]glycerol into CL (2-fold, p<0.05) compared to controls indicating elevation in de novo CL biosynthesis. The reason for this was an increase in [1,3-3H]glycerol uptake and increase in activity and mRNA expression of the CL biosynthetic enzymes. In contrast, expression of FATP-1 resulted a reduction in incorporation of [1,3-3H]glycerol into CL (65%, p<0.05) indicating reduced CL synthesis. [1,3-3H]Glycerol uptake was unaltered whereas activity of cytidine-5′-diphosphate-1,2-diacyl-sn-glycerol synthetase (CDS) and CDS-2 mRNA expression were reduced in FATP-1 expressing cells compared to control. In addition, in vitro CDS activity was reduced by exogenous addition of oleoyl-Coenzyme A. The data indicate that CL de novo biosynthesis may be regulated by FATP-1 through CDS-2 expression in HEK 293 cells

Fat in flames: Influence of cytokines and pattern recognition receptors on adipocyte lipolysis

© 2015 the American Physiological Society. Adipose tissue has the largest capacity to store energy in the body and provides energy through the release of free fatty acids during times of energy need. Different types of immune cells are recruited to adipose tissue under various physiological conditions, indicating that these cells contribute to the regulation of adipose tissue. One major pathway influenced by a number of immune cells is the release of free fatty acids through lipolysis during both physiological (e.g., cold stress) and pathophysiological processes (e.g., obesity, type 2 diabetes). Adipose tissue expansion during obesity leads to immune cell infiltration and adipose tissue remodeling, a homeostatic process that promotes inflammation in adipose tissue. The release of proinflammatory cytokines stimulates lipolysis and causes insulin resistance, leading to adipose tissue dysfunction and systemic disruptions of metabolism. This review focuses on the interactions of cytokines and other inflammatory molecules that regulate adipose tissue lipolysis during physiological and pathophysiological states

2-deoxyglucose inhibits induction of chemokine expression in 3T3-L1 adipocytes and adipose tissue explants

© 2016 The Obesity Society Objective: To determine the influence of glycolytic inhibition on the adipocyte inflammatory response. Methods: To determine the effect of 2-deoxyglucose (2-DOG) on the inflammatory response, mature 3T3-L1 adipocytes were co-treated with 2-DOG and LPS or TNF. To determine the effect of endoplasmic reticulum stress on TNF-induced induction of chemokines, adipocytes were pretreated with thapsigargin or salubrinal. Chemokine mRNA levels were determined using quantitative real-time PCR, and secretion of CCL2 was determined by Western blot. Results: 2-DOG treatment reduced the ability of LPS and TNF to induce CCL2 mRNA levels and reduced secreted CCL2 protein levels in a dose-dependent manner. A similar pattern of mRNA regulation was observed for other chemokines. The attenuation of TNF-induced CCL2 mRNA levels occurred regardless of whether glucose or pyruvate was present in the media, suggesting that mechanisms other than glycolysis might mediate the observed effects. Treatment with the endoplasmic reticulum stressor thapsigargin and the endoplasmic reticulum signaling activator salubrinal reduced chemokine mRNA levels similarly to 2-DOG. Conclusions: Collectively, our data indicate that 2-DOG suppresses inflammatory chemokine induction in adipocytes. The effects of 2-DOG do not seem to be linked to glycolysis but correlate with endoplasmic reticulum stress activation

Deaths from Norovirus among the Elderly, England and Wales

Norovirus may be associated with ≈80 deaths/year

On the Clustering of Sub-millimeter Galaxies

We measure the angular two-point correlation function of sub-millimeter galaxies (SMGs) from 1.1-millimeter imaging of the COSMOS field with the AzTEC camera and ASTE 10-meter telescope. These data yields one of the largest contiguous samples of SMGs to date, covering an area of 0.72 degrees^2 down to a 1.26 mJy/beam (1-sigma) limit, including 189 (328) sources with S/N greater than 3.5 (3). We can only set upper limits to the correlation length r_0, modeling the correlation function as a power-law with pre-assigned slope. Assuming existing redshift distributions, we derive 68.3% confidence level upper limits of r_0 < 6-8 h^-1 Mpc at 3.7 mJy, and r_0 < 11-12 h^-1 Mpc at 4.2 mJy. Although consistent with most previous estimates, these upper limits imply that the real r_0 is likely smaller. This casts doubts on the robustness of claims that SMGs are characterized by significantly stronger spatial clustering, (and thus larger mass), than differently selected galaxies at high-redshift. Using Monte Carlo simulations we show that even strongly clustered distributions of galaxies can appear unclustered when sampled with limited sensitivity and coarse angular resolution common to current sub-millimeter surveys. The simulations, however, also show that unclustered distributions can appear strongly clustered under these circumstances. From the simulations, we predict that at our survey depth, a mapped area of two degrees^2 is needed to reconstruct the correlation function, assuming smaller beam sizes of future surveys (e.g. the Large Millimeter Telescope's 6" beam size). At present, robust measures of the clustering strength of bright SMGs appear to be below the reach of most observations.Comment: 23 pages, 8 figures, accepted for publication in The Astrophysical Journa

SM-1 (APPR-1) RESEARCH AND DEVELOPMENT PROGRAM ACTIVITY BUILDUP PROGRAM. TASK I. Status Report for February to November 1958

Results are given of experimental work performed from February to November 1958 to determine the nature and extent of the build-up of radioactivity in the primary system of the SM-1 (APPR-1). The results of radiochemical and chemical analyses of primary water, circulating crud, and deposits removed from metal test specimens are presented. The relationships between build-up of activity and calendar hours, reactor operation, and crud levels are given. The methods and results of dose rate measurements made on the primary system components are reported. (auth