Rowett Institute of Nutrition and Health

Bucksburn, United Kingdom

Rowett Institute of Nutrition and Health

Bucksburn, United Kingdom
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Xu P.,Baylor College of Medicine | He Y.,Baylor College of Medicine | Cao X.,Baylor College of Medicine | Valencia-Torres L.,Rowett Institute of Nutrition and Health | And 13 more authors.
Biological Psychiatry | Year: 2017

Background Neural networks that regulate binge eating remain to be identified, and effective treatments for binge eating are limited. Methods We combined neuroanatomic, pharmacologic, electrophysiological, Cre-lox, and chemogenetic approaches to investigate the functions of 5-hydroxytryptamine (5-HT) 2C receptor (5-HT2CR) expressed by dopamine (DA) neurons in the regulation of binge-like eating behavior in mice. Results We showed that 5-HT stimulates DA neural activity through a 5-HT2CR-mediated mechanism, and activation of this midbrain 5-HT→DA neural circuit effectively inhibits binge-like eating behavior in mice. Notably, 5-HT medications, including fluoxetine, d-fenfluramine, and lorcaserin (a selective 5-HT2CR agonist), act on 5-HT2CRs expressed by DA neurons to inhibit binge-like eating in mice. Conclusions We identified the 5-HT2CR population in DA neurons as one potential target for antibinge therapies, and provided preclinical evidence that 5-HT2CR agonists could be used to treat binge eating. © 2016 Society of Biological Psychiatry

Anderson R.L.,University of Nottingham | Anderson R.L.,Rowett Institute of Nutrition and Health | Randall M.D.,University of Nottingham | Chan S.L.F.,University of Nottingham
European Journal of Pharmacology | Year: 2013

Recent interest in the endocrine pancreas has revealed the presence of a functional endocannabinoid system in pancreatic islets, however, the effects of endocannabinoids and cannabinoid CB receptor activation on downstream signalling and on insulin release still remains unclear. In the current study, a variety of purported cannabinoid CB receptor agonists and antagonists were evaluated for their effects on insulin secretion. In fresh rat isolated islets, the endocannabinoid anandamide caused a glucose-dependent, concentration-dependent inhibition of insulin release, with two populations of islets being identified based on their sensitivity to anandamide. Methanandamide (a non-hydrolysable analogue of anandamide) elicited similar inhibition of insulin secretion, comparable to the responses obtained with anandamide-sensitive islets, suggesting that the islet responsiveness may be due to differences in local metabolism of anandamide. The antagonists O-2050 (CB1) and AM630 (CB2) failed to reveal the involvement of cannabinoid receptors in the inhibitory activity of anandamide on insulin release. Inhibition of fatty acid amide hydrolase (FAAH) with URB597 did not alter basal or glucose-induced insulin secretion, suggesting that endogenous islet endocannabinoids do not affect insulin release, or that islet FAAH content is low. URB597 also failed to affect the inhibitory actions of anandamide on insulin release in fresh isolated islets. However, in islets following overnight culture, anandamide caused augmentation of basal and glucose-mediated insulin release. The effects of cannabinoid agents on insulin secretion described in this study does not identify a precise mode of action but points to important modulation which may be dependent on local metabolism and prevailing cellular conditions. Copyright © 2013 Published by Elsevier B.V. All rights reserved.

Lawley T.D.,Wellcome Trust Sanger Institute | Clare S.,Wellcome Trust Sanger Institute | Walker A.W.,Wellcome Trust Sanger Institute | Stares M.D.,Wellcome Trust Sanger Institute | And 13 more authors.
PLoS Pathogens | Year: 2012

Relapsing C. difficile disease in humans is linked to a pathological imbalance within the intestinal microbiota, termed dysbiosis, which remains poorly understood. We show that mice infected with epidemic C. difficile (genotype 027/BI) develop highly contagious, chronic intestinal disease and persistent dysbiosis characterized by a distinct, simplified microbiota containing opportunistic pathogens and altered metabolite production. Chronic C. difficile 027/BI infection was refractory to vancomycin treatment leading to relapsing disease. In contrast, treatment of C. difficile 027/BI infected mice with feces from healthy mice rapidly restored a diverse, healthy microbiota and resolved C. difficile disease and contagiousness. We used this model to identify a simple mixture of six phylogenetically diverse intestinal bacteria, including novel species, which can re-establish a health-associated microbiota and clear C. difficile 027/BI infection from mice. Thus, targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. Further, we demonstrate a rational approach to harness the therapeutic potential of health-associated microbial communities to treat C. difficile disease and potentially other forms of intestinal dysbiosis. © 2012 Lawley et al.

Hanon E.A.,University of Aberdeen | Hanon E.A.,Rowett Institute of Nutrition and Health | Hanon E.A.,University of Strasbourg | Routledge K.,University of Aberdeen | And 4 more authors.
Journal of Neuroendocrinology | Year: 2010

Recent studies have characterised a retrograde mechanism whereby the pineal hormone melatonin acts in the pars tuberalis (PT) of the pituitary gland to control thyroid hormone action in the hypothalamus, leading to changes in seasonal reproductive function. This involves the release of thyroid-stimulating hormone (TSH) from PT that activates type II deiodinase (DIO2) gene expression in hypothalamic ependymal cells, locally generating biologically active T3, and thus triggering a neuroendocrine cascade. In the present study, we investigated whether a similar regulatory mechanism operates in the European hamster. This species utilises both melatonin signalling and a circannual timer to time the seasonal reproductive cycle. We found that expression of βTSH RNA in the PT was markedly increased under long compared to short photoperiod, whereas TSH receptor expression was localised in the ependymal cells lining the third ventricle, and in the PT, where its expression varied with time and photoperiod. In the ependymal cells at the base of the third ventricle, DIO2 and type III deiodinase (DIO3) expression was reciprocally regulated, with DIO2 activated under long and repressed under short photoperiod, and the reverse case for DIO3. These data are consistent with recent observations in sheep, and suggest that the PT TSH third ventricle-ependymal cell relay plays a conserved role in initiating the photoperiodic response in both long- and short-day breeding mammals. © 2009 The Authors. Journal Compilation © 2009 Blackwell Publishing Ltd.

Louis P.,University of Aberdeen | Young P.,University of Aberdeen | Holtrop G.,Rowett Institute of Nutrition and Health | Flint H.J.,University of Aberdeen
Environmental Microbiology | Year: 2010

Butyrate-producing bacteria play an important role in the human colon, supplying energy to the gut epithelium and regulating host cell responses. In order to explore the diversity and culturability of this functional group, we designed degenerate primers to amplify butyryl-CoA:acetate CoA-transferase sequences from faecal samples provided by 10 healthy volunteers. Eighty-eight per cent of amplified sequences showed > 98% DNA sequence identity to CoA-transferases from cultured butyrate-producing bacteria, and these fell into 12 operational taxonomic units (OTUs). The four most prevalent OTUs corresponded to Eubacterium rectale, Roseburia faecis, Eubacterium hallii and an unnamed cultured species SS2/1. The remaining 12% of sequences, however, belonged to 20 OTUs that are assumed to come from uncultured butyrate-producing strains. Samples taken after ingestion of inulin showed significant (P = 0.019) increases in Faecalibacterium prausnitzii. Because several of the dominant butyrate producers differ in their DNA % G+C content, analysis of thermal melt curves obtained for PCR amplicons of the butyryl-CoA:acetate CoA-transferase gene provides a convenient and rapid qualitative assessment of the major butyrate producing groups present in a given sample. This type of analysis therefore provides an excellent source of information on functionally important groups within the colonic microbial community. © 2009 Society for Applied Microbiology and Blackwell Publishing Ltd.

Johnstone A.M.,University of Aberdeen | Lobley G.E.,University of Aberdeen | Horgan G.W.,Rowett Institute of Nutrition and Health | Bremner D.M.,University of Aberdeen | And 3 more authors.
British Journal of Nutrition | Year: 2011

There are concerns that weight-loss (WL) diets based on very low carbohydrate (LC) intake have a negative impact on antioxidant status and biomarkers of cardiovascular and metabolic health. Obese men (n 16) participated in a randomised, cross-over design diet trial, with food provided daily, at approximately 8•3 MJ/d (approximately 70 % of energy maintenance requirements). They were provided with two high-protein diets (30 % of energy), each for a 4-week period, involving a LC (4 % carbohydrate) and a moderate carbohydrate (MC, 35 % carbohydrate) content. Body weight was measured daily, and weekly blood samples were collected. On average, subjects lost 6•75 and 4•32 kg of weight on the LC and MC diets, respectively (P < 0•001, sed 0•350). Although the LC and MC diets were associated with a small reduction in plasma concentrations of retinol, vitamin E (α- tocopherol) and β-cryptoxanthin (P < 0•005), these were still above the values indicative of deficiency. Interestingly, plasma vitamin C concentrations increased on consumption of the LC diet (P < 0•05). Plasma markers of insulin resistance (P < 0•001), lipaemia and inflammation (P < 0•05, TNF-α and IL-10) improved similarly on both diets. There was no change in other cardiovascular markers with WL. The present data suggest that a LC WL diet does not impair plasma indices of cardiometabolic health, at least within 4 weeks, in otherwise healthy obese subjects. In general, improvements in metabolic health associated with WL were similar between the LC and MC diets. Antioxidant supplements may be warranted if LC WL diets are consumed for a prolonged period. © 2011 The Authors.

Stubbs R.J.,Rowett Institute of Nutrition and Health | Stubbs R.J.,University of Derby | O'Reilly L.M.,Rowett Institute of Nutrition and Health | Whybrow S.,University of Aberdeen | And 5 more authors.
British Journal of Nutrition | Year: 2014

To date, no study has directly and simultaneously measured the discrepancy between what people actually eat and what they report eating under observation in the context of energy balance (EB). The present study aimed to objectively measure the 'extent' and 'nature' of misreporting of dietary intakes under conditions in which EB and feeding behaviour were continuously monitored. For this purpose, a total of fifty-nine adults were recruited for 12 d, involving two 3 d overt phases and two 3 d covert phases of food intake measurement in a randomised cross-over design. Subjects had ad libitum access to a variety of familiar foods. Food intake was covertly measured using a feeding behaviour suite to establish actual energy and nutrient intakes. During the overt phases, subjects were instructed to self-report food intake using widely accepted methods. Misreporting comprised two separate and synchronous phenomena. Subjects decreased energy intake (EI) when asked to record their food intake (observation effect). The effect was significant in women ( - 8 %, P< 0·001) but not in men ( - 3 %, P< 0·277). The reported EI was 5 to 21 % lower (reporting effect) than the actual intake, depending on the reporting method used. Semi-quantitative techniques gave larger discrepancies. These discrepancies were identical in men and women and non-macronutrient specific. The 'observation' and 'reporting' effects combined to constitute total misreporting, which ranged from 10 to 25 %, depending on the intake measurement assessed. When studied in a laboratory environment and EB was closely monitored, subjects under-reported their food intake and decreased the actual intake when they were aware that their intake was being monitored. © The Authors 2014.

Baines D.L.,St George's, University of London | Albert A.P.,St George's, University of London | Hazeli M.J.,St Helier Hospital | Gambling L.,Rowett Institute of Nutrition and Health | And 2 more authors.
Pflugers Archiv European Journal of Physiology | Year: 2010

Bacterial lipopolysaccharides (LPS) are potent inducers of proinflammatory signaling pathways via the activation of nuclear factor-kappa B (NF-KB) and mitogenactivated protein kinase (MAPK), causing changes in the processes that control lung fluid homeostasis and contributing to the pathogenesis of lung disease. In human H441 airway epithelial cells, incubation of cells with 15 ng ml-1 LPS caused a significant reduction in amiloride-sensitive / sc from 15±2 to 8±2 uA cm-2 (p=0.01, n=13) and a shift in IC50 amiloride of currents from 6.8 × 10 -7 to 6.4×10-6 M. This effect was associated with a decrease in the activity of 5 pS, highly Na+ selective, amiloride-sensitive <1 u.M. channels (HSC) and an increase in the activity of ∼18 pS, nonselective, amiloride-sensitive >10 uM cation channels (NSC) in the apical membrane. LPS decreased aENaC mRNA and protein abundance, inferring that LPS inhibited aENaC gene expression. This correlated with the decrease in HSC activity, indicating that these channels, but not NSCs, were comprised of at least aENaC protein. LPS increased NF- KB DNA binding activity and phosphorylation of extracellular signal-related kinase (ERK) 1/2, but decreased phosphorylation of ERKS in H.441 cells. Pretreatment of monolayers with PD98059 (20 uM) inhibited ERK1/2 phosphorylation, promoted phosphorylation of ERK5, increased aENaC protein abundance, and reversed the effect of LPS on I80 and the shift in amiloride sensitivity. Inhibitors of NF-KB activation were without effect. Taken together, our data indicate that LPS acts via ERK signaling pathways to decrease ccENaC transcription, reducing HSC/ ENaC channel abundance, activity, and transepithelial Na+ transport in H441 airway epithelial cells.

Reuter M.,University of Edinburgh | Reuter M.,Erasmus Medical Center | Hayward N.J.,University of Aberdeen | Hayward N.J.,Rowett Institute of Nutrition and Health | And 4 more authors.
Journal of the Royal Society Interface | Year: 2014

Mechanogated channels are fundamental components of bacterial cells that enable retention of physical integrity during extreme increases in cell turgor. Optical tweezers combined with microfluidics have been used to study the fate of individual Escherichia coli cells lacking such channels when subjected to a bursting stress caused by increased turgor. Fluorescence-activated cell sorting and electron microscopy complement these studies. These analyses show that lysis occurs with a high probability, but the precise path differs between individual cells. By monitoring the loss of cytoplasmic green fluorescent protein, we have determined that some cells release this protein but remain phase dark (granular) consistent with the retention of the majority of large proteins. By contrast, most cells suffer cataclysmic wall failure leading to loss of granularity but with the retention of DNA and overall cell shape (protein-depleted ghosts). The time span of these events induced by hypo-osmotic shock varies but is of the order of milliseconds. The data are interpreted in terms of the timing of mechanosensitive channel gating relative to osmotically induced water influx. © 2013 The Authors. Published by the Royal Society.

Ostertag L.M.,University of Aberdeen | O'Kennedy N.,Provexis plc | Horgan G.W.,Rowett Institute of Nutrition and Health | Kroon P.A.,UK Institute of Food Research | And 2 more authors.
Molecular Nutrition and Food Research | Year: 2011

Scope: Bioactive polyphenols from fruits, vegetables, and beverages have anti-platelet effects and may thus affect the development of cardiovascular disease. We screened the effects of 26 low molecular weight phenolic compounds on two in vitro measures of human platelet function. Methods and results: After platelets had been incubated with one of 26 low molecular weight phenolic compounds in vitro, collagen-induced human platelet aggregation and in vitro TRAP-induced P-selectin expression (as marker of platelet activation) were assessed. Incubation of platelet-rich plasma from healthy volunteers with 100μmol/L hippuric acid, pyrogallol, catechol, or resorcinol significantly inhibited collagen-induced platelet aggregation (all p<0.05; n≥15). Incubation of whole blood with concentrations of 100μmol/L salicylic acid, p-coumaric acid, caffeic acid, ferulic acid, 4-hydroxyphenylpropionyl glycine, 5-methoxysalicylic acid, and catechol significantly inhibited TRAP-induced surface P-selectin expression (all p<0.05; n=10). Incubation with lower concentrations of phenolics affected neither platelet aggregation nor activation. Conclusion: As concentrations of 100μmol/L are unlikely to be reached in the circulation, it is doubtful whether consumption of dietary phenolics in nutritionally attainable amounts plays a major role in inhibition of platelet activation and aggregation in humans. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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