Propionate functions as a feeding state-dependent regulatory metabolite to counter proinflammatory signaling linked to nutrient load and obesity.

The authors thank Drs. Antonio Murgia and Ben McNally of the University of Cambridge Biochemistry Department for their contributions to metabolomics and lipidomic data processing. They thank and acknowledge the assistance of the National Heart, Lung, and Blood Institute DNA Sequencing and Genomics Core in performing the RNA library sequencing and the National Heart, Lung, and Blood Institute Flow Cytometry Core for performing the flow cytometry.Peer reviewe

Enhanced hepatic respiratory capacity and altered lipid metabolism support metabolic homeostasis during short-term hypoxic stress.

BACKGROUND: Tissue hypoxia is a key feature of several endemic hepatic diseases, including alcoholic and non-alcoholic fatty liver disease, and organ failure. Hypoxia imposes a severe metabolic challenge on the liver, potentially disrupting its capacity to carry out essential functions including fuel storage and the integration of lipid metabolism at the whole-body level. Mitochondrial respiratory function is understood to be critical in mediating the hepatic hypoxic response, yet the time-dependent nature of this response and the role of the respiratory chain in this remain unclear. RESULTS: Here, we report that hepatic respiratory capacity is enhanced following short-term exposure to hypoxia (2 days, 10% O2) and is associated with increased abundance of the respiratory chain supercomplex III2+IV and increased cardiolipin levels. Suppression of this enhanced respiratory capacity, achieved via mild inhibition of mitochondrial complex III, disrupted metabolic homeostasis. Hypoxic exposure for 2 days led to accumulation of plasma and hepatic long chain acyl-carnitines. This was observed alongside depletion of hepatic triacylglycerol species with total chain lengths of 39-53 carbons, containing palmitic, palmitoleic, stearic, and oleic acids, which are associated with de novo lipogenesis. The changes to hepatic respiratory capacity and lipid metabolism following 2 days hypoxic exposure were transient, becoming resolved after 14 days in line with systemic acclimation to hypoxia and elevated circulating haemoglobin concentrations. CONCLUSIONS: The liver maintains metabolic homeostasis in response to shorter term hypoxic exposure through transient enhancement of respiratory chain capacity and alterations to lipid metabolism. These findings may have implications in understanding and treating hepatic pathologies associated with hypoxia.GlaxoSmithKlin

The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination.

The microbiota is now recognized as a key influence on the host immune response in the central nervous system (CNS). As such, there has been some progress toward therapies that modulate the microbiota with the aim of limiting immune-mediated demyelination, as occurs in multiple sclerosis. However, remyelination-the regeneration of myelin sheaths-also depends upon an immune response, and the effects that such interventions might have on remyelination have not yet been explored. Here, we show that the inflammatory response during CNS remyelination in mice is modulated by antibiotic or probiotic treatment, as well as in germ-free mice. We also explore the effect of these changes on oligodendrocyte progenitor cell differentiation, which is inhibited by antibiotics but unaffected by our other interventions. These results reveal that high combined doses of oral antibiotics impair oligodendrocyte progenitor cell responses during remyelination and further our understanding of how mammalian regeneration relates to the microbiota.This work was supported by grants from UK Multiple Sclerosis Society, The British Trust for the Myelin Project, MedImmune, The Adelson Medical Research Foundation, Wellcome Trust, BBSRC, the Leverhulme Trust and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute. CEM was supported by grants from the Jean Shanks Foundation and the James Baird Fund, AGF was supported by an ECTRIMS fellowship and OBZ received a BIRAX fellowship

Ornamental plants: annual reports and research reviews

Ohio State University Extension Nursery, Landscape, and Turf Team Directory: 1998 / Jack Kerrigan -- Floriculture Industry Roundtable of Ohio: 1998 / Charles Behnke -- Ohio State University Extension Buckeye Yard and Garden Line / James A. Chatfield, Pamela J. Bennett, Joseph F. Boggs, Gary Y. Gao, Jane C. Martin, David J. Shetlar and Randall H. Zondag -- Environmental and cultural problems of ornamental plants in Ohio: 1997 / Pamela J. Bennett and Jane C. Martin -- Insect and mite activity noted in Ohio nurseries and landscapes: 1997 / Joseph F. Boggs, David J. Shetlar, Jane C. Martin, Pamela J. Bennett, James A. Chatfield, Gary Y. Gao and Chris Carlson -- Summary of ornamental diseases in Ohio: 1997 / James A. Chatfield, Nancy J. Taylor, Stephen N. Nameth, Chris Carlson, Joseph F. Boggs, Jane C. Martin, Dan Balser and David Madison -- Weed problems in Ohio landscapes and nurseries: 1997 / Gary Y. Gao, Joseph F. Boggs, Pamela J. Bennett, Jane C. Martin, Mary Ann Rose, Joseph W. Rimelspach, Randall H. Zondag and William E. Pound -- Wildlife problems in Ohio landscapes: 1997 / Gary Y. Gao, Joseph F. Boggs, Jane C. Martin, Charles T. Behnke and James A. Chatfield -- Summary of turf cultural and disease problems in 1997 / Gary Y. Gao, Joseph F. Boggs, Pamela J. Bennett, Jane C. Martin, Joseph W. Rimelspach and James A. Chatfield -- Master Gardeners serve Ohio / Marianne Riofrio -- The greening of Poland's nurseries / Kenneth D. Cochran and Wojtek Grabczewski -- The marketing potential of Ginkgo biloba in the United States / Kenneth D. Cochran -- Composts in the Landscape: Effects on Soil pH and plant growth / Mary Ann Rose and Hao Wang -- How to optimize disease control using composts / Harry A. J. Hoitink, Wei-Zheng Zhang, David Y. Han, Alexandra G. Stone, Matthew S. Krause and Warren A. Dick -- The flowering sequence of ornamental plants as a tool for predicting the phenology of insect pests / Daniel A. Herms -- Reducing maintenance costs may mean selecting plants with the fewest flaws / T. Davis Sydnor-- Comprehensive aesthetic evaluations of crabapples at Secrest Arboretum in Wooster: 1993-1997 / Erik A. Draper, James A. Chatfield, Kenneth D. Cochran, Peter W. Bristol and David E. Allen -- Precision control of microirrigation for container-grown mini-roses / Robert C. Hansen, Ted H. Short, C. C. Pasian and R. Peter Fynn -- Red thread (Laetisaria fuciformis) control study on perennial ryegrass / Joseph W. Rimelspach, Kerry Kline, Karl Danneberger and Michael Boehm-- Red thread (Laetisaria fuciformis) control study on Kentucky bluegrass / Joseph W. Rimelspach, Kerry Kline, Karl Danneberger and Michael Boehm -- Red thread - from novelty to nuisance / Joseph W. Rimelspach -- Chrysanthemum cultivars differ in response to photoperiod when grown under far-red absorbing filters / M. J. McMahon -- Improving fuchsia cutting performance by grafting / D. M. Napier and M. J. McMahon -- Paint/paclobutrazol mix on the inside surface of rooting wedge cells to control poinsettia cutting height / Claudio C. Pasian -- Response of poinsettias to paclobutrazol in paint applications / Claudio C. Pasian and Daniel K. Struve -- Dynamic transpiration of highly stressed container-grown Acer rubrum / Ted H. Short, Ahmet Irvem and Robert C. Hansen -- Effects of temperature on the development of Asiatic Lilies / J. Steininger and C. C. Pasian-- New publications for 1997-199

Multi-omics and imaging mass cytometry characterization of human kidneys to identify pathways and phenotypes associated with impaired kidney function.

We are grateful to the donors, donor families, and NHS Blood and Transplant service and the Cambridge Biorepository for Translational Medicine (CBTM) for access to human samples; Karolina Nilsson (Medicinal Chemistry, AstraZeneca) for providing the cytosolic phospholipase A2 inhibitor; and Julia Lindgren (Discovery Sciences, AstraZenca) for coordinating the RNA-sequencing workflow.Peer reviewe

Brown and beige adipose tissue regulate systemic metabolism through a metabolite interorgan signaling axis.

Brown and beige adipose tissue are emerging as distinct endocrine organs. These tissues are functionally associated with skeletal muscle, adipose tissue metabolism and systemic energy expenditure, suggesting an interorgan signaling network. Using metabolomics, we identify 3-methyl-2-oxovaleric acid, 5-oxoproline, and β-hydroxyisobutyric acid as small molecule metabokines synthesized in browning adipocytes and secreted via monocarboxylate transporters. 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid induce a brown adipocyte-specific phenotype in white adipocytes and mitochondrial oxidative energy metabolism in skeletal myocytes both in vitro and in vivo. 3-methyl-2-oxovaleric acid and 5-oxoproline signal through cAMP-PKA-p38 MAPK and β-hydroxyisobutyric acid via mTOR. In humans, plasma and adipose tissue 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid concentrations correlate with markers of adipose browning and inversely associate with body mass index. These metabolites reduce adiposity, increase energy expenditure and improve glucose and insulin homeostasis in mouse models of obesity and diabetes. Our findings identify beige adipose-brown adipose-muscle physiological metabokine crosstalk.Diabetes UK RD Lawrence Fellowship (16/0005382

Brown and beige adipose tissue regulate systemic metabolism through a metabolite interorgan signaling axis.

Brown and beige adipose tissue are emerging as distinct endocrine organs. These tissues are functionally associated with skeletal muscle, adipose tissue metabolism and systemic energy expenditure, suggesting an interorgan signaling network. Using metabolomics, we identify 3-methyl-2-oxovaleric acid, 5-oxoproline, and β-hydroxyisobutyric acid as small molecule metabokines synthesized in browning adipocytes and secreted via monocarboxylate transporters. 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid induce a brown adipocyte-specific phenotype in white adipocytes and mitochondrial oxidative energy metabolism in skeletal myocytes both in vitro and in vivo. 3-methyl-2-oxovaleric acid and 5-oxoproline signal through cAMP-PKA-p38 MAPK and β-hydroxyisobutyric acid via mTOR. In humans, plasma and adipose tissue 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid concentrations correlate with markers of adipose browning and inversely associate with body mass index. These metabolites reduce adiposity, increase energy expenditure and improve glucose and insulin homeostasis in mouse models of obesity and diabetes. Our findings identify beige adipose-brown adipose-muscle physiological metabokine crosstalk.Diabetes UK RD Lawrence Fellowship (16/0005382