Regulation and Maintenance of Vascular Tone and Patency in Cardiovascular Health and Disease

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Despite numerous advances in health care practices, cardiovascular disease still remains the leading cause of morbidity and mortality worldwide. Perhaps the most important consequence of cardiovascular disease is the interruption of blood flow to organs such as the heart and brain, resulting in the clinical presentation of a heart attack or stroke. As such, the regulation of vascular tone and the maintenance of vascular patency are vital for the preservation of cardiovascular health. Central to this process is the vascular endothelium. The endothelium is vital for the regulation of vascular tone and the maintenance of vascular homeostasis, as it releases factors such as nitric oxide, hydrogen sulfide, endothelialdependent hyperpolarizing factor, and prostacyclin tha

Metabolic remodeling of white adipose tissue in obesity

Adipose tissue metabolism is a critical regulator of adiposity and whole body energy expenditure; however, metabolic changes that occur in white adipose tissue (WAT) with obesity remain unclear. The purpose of this study was to understand the metabolic and bioenergetic changes occurring in WAT with obesity. Wild-type (C57BL/6J) mice fed a high-fat diet (HFD) showed significant increases in whole body adiposity, had significantly lower V̇o2, V̇co2, and respiratory exchange ratios, and demonstrated worsened glucose and insulin tolerance compared with low-fat-fed mice. Metabolomic analysis of WAT showed marked changes in lipid, amino acid, carbohydrate, nucleotide, and energy metabolism. Tissue levels of succinate and malate were elevated, and metabolites that could enter the Krebs cycle via anaplerosis were mostly diminished in high-fat-fed mice, suggesting altered mitochondrial metabolism. Despite no change in basal oxygen consumption or mitochondrial DNA abundance, citrate synthase activity was decreased by more than 50%, and responses to FCCP were increased in WAT from mice fed a high-fat diet. Moreover, Pgc1a was downregulated and Cox7a1 upregulated after 6 wk of HFD. After 12 wk of high-fat diet, the abundance of several proteins in the mitochondrial respiratory chain or matrix was diminished. These changes were accompanied by increased Parkin and Pink1, decreased p62 and LC3-I, and ultrastructural changes suggestive of autophagy and mitochondrial remodeling. These studies demonstrate coordinated restructuring of metabolism and autophagy that could contribute to the hypertrophy and whitening of adipose tissue in obesity

Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis

National Institutes of Health grants GM-38765 and P50-DE016191 (C.N.S.), Welcome Trust Programme grant 086867/Z/08/Z (R.J.F. and M.P.) and Project grant 085903/Z/08 (R.J.F.) and Arthritis Research Campaign UK fellowships 18445 and 18103 (to L.V.N. and D.C., respectively). M.S. received a National Research Service Award from the NHLBI (HL087526)

12-Lipoxygenase regulates cold adaptation and glucose metabolism by producing the omega-3 lipid 12-HEPE from brown Fat

Distinct oxygenases and their oxylipin products have been shown to participate in thermogenesis by mediating physiological adaptations required to sustain body temperature. Since the role of the lipoxygenase (LOX) family in cold adaptation remains elusive, we aimed to investigate whether, and how, LOX activity is required for cold adaptation and to identify LOX-derived lipid mediators that could serve as putative cold mimetics with therapeutic potential to combat diabetes. By utilizing mass-spectrometry-based lipidomics in mice and humans, we demonstrated that cold and beta 3-adrenergic stimulation could promote the biosynthesis and release of 12-LOX metabolites from brown adipose tissue (BAT). Moreover, 12-LOX ablation in mouse brown adipocytes impaired glucose uptake and metabolism, resulting in blunted adaptation to the cold in vivo. The cold-induced 12-LOX product 12-HEPE was found to be a batokine that improves glucose metabolism by promoting glucose uptake into adipocytes and skeletal muscle through activation of an insulin-like intracellular signaling pathway304768783FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2017/02684This work was supported in part by US National Institutes of Health (NIH) grants R01DK077097 and R01DK102898 (to Y.-H.T.); R01HL106173 and P01GM095467 (to M.S.); R01DK099511 (to L.J.G.) and P30DK036836 (to Joslin Diabetes Center's Diabetes Research Center) from the National Institute of Diabetes and Digestive and Kidney Diseases; and by US Army Medical Research grant W81XWH-17-1-0428 (to Y.-H.T.). L.O.L. was supported by an American Diabetes Association post-doctoral fellowship (1-16-PDF-063) and by the São Paulo Research Foundation (FAPESP) grant 2017/02684. M.D.L. was supported by NIH grants T32DK007260, F32DK102320, and K01DK111714. K.v.L. was supported by the grant R21NS087165. A.B. was supported by a Deutsche Forschungsgemeinschaft research fellowship (BA 4925/1-1) and the Deutsches Zentrum für Herz-Kreislauf-Forschung. B.E.S. is supported by an NRSA from the NIH (HL136044). We thank A. Clermont, A. Dean, and K. Longval of the Joslin Diabetes Center Physiology core. We also would like to thank Dr. Fabio Tucci of Epigen Biosciences, San Diego, who synthesized LOXBlock-1. We apologize to colleagues whose work we could not cite due to space limitation