| 1. |
- Shen, Xiaoli, et al.
(författare)
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Composition and origin of PM2.5 aerosol particles in the upper Rhine valley in summer
- 2019
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 19:20, s. 13189-13208
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a 6-week measurement campaign in summer 2016 at a rural site about 11 km north of the city of Karlsruhe in southwest Germany in order to study the chemical composition and origin of aerosols in the upper Rhine valley. In particular, we deployed a single-particle mass spectrometer (LAAPTOF) and an aerosol mass spectrometer (AMS) to provide complementary chemical information on aerosol particles smaller than 2.5 mu m. For the entire measurement period, the total aerosol particle mass was dominated by sodium salts, contributing on average (36 +/- 27) % to the total single particles measured by the LAAPTOF. The total particulate organic compounds, sulfate, nitrate, and ammonium contributed on average (58 +/- 12) %, (22 +/- 7) %, (10 +/- 1) %, and (9 +/- 3) % to the total non-refractory particle mass measured by the AMS. Positive matrix factorization (PMF) analysis for the AMS data suggests that the total organic aerosol (OA) consisted of five components, including (9 +/- 7) % hydrocarbon-like OA (HOA), (16 +/- 11) % semi-volatile oxygenated OA (SV-OOA), and (75 +/- 15) % low-volatility oxygenated OA (LV-OOA). The regional transport model COSMO-ART was applied for source apportionment and to achieve a better understanding of the impact of complex transport patterns on the field observations. Combining field observations and model simulations, we attributed high particle numbers and SO2 concentrations observed at this rural site to industrial emissions from power plants and a refinery in Karlsruhe. In addition, two characteristic episodes with aerosol particle mass dominated by sodium salts particles comprising (70 +/- 24) % of the total single particles and organic compounds accounting for (77 +/- 6) % of total non-refractory species, respectively, were investigated in detail. For the first episode, we identified relatively fresh and aged sea salt particles originating from the Atlantic Ocean more than 800 km away. These particles showed markers like m/z 129 C5H7NO3+, indicating the influence of anthropogenic emissions modifying their composition, e.g. from chloride to nitrate salts during the long-range transport. For a 3 d episode including high organic mass concentrations, model simulations show that on average (74 +/- 7) % of the particulate organics at this site were of biogenic origin. Detailed model analysis allowed us to find out that three subsequent peaks of high organic mass concentrations originated from different sources, including local emissions from the city and industrial area of Karlsruhe, regional transport from the city of Stuttgart (similar to 64 km away), and potential local night-time formation and growth. Biogenic (forest) and anthropogenic (urban) emissions were mixed during transport and contributed to the formation of organic particles. In addition, topography, temperature inversion, and stagnant meteorological conditions also played a role in the build-up of higher organic particle mass concentrations. Furthermore, the model was evaluated using field observations and corresponding sensitivity tests. The model results show good agreement with trends and concentrations observed for several trace gases (e.g. O-3, NO2, and SO2) and aerosol particle compounds (e.g. ammonium and nitrate). However, the model underestimates the number of particles by an order of magnitude and underestimates the mass of organic particles by a factor of 2.3. The discrepancy was expected for particle number since the model does not include all nucleation processes. The missing organic mass indicates either an underestimated regional background or missing sources and/or mechanisms in the model, like night-time chemistry. This study demonstrates the potential of combining comprehensive field observations with dedicated transport modelling to understand the chemical composition and complex origin of aerosols.
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| 2. |
- Bake, Tina, et al.
(författare)
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Ghrelin Receptor Stimulation of the Lateral Parabrachial Nucleus in Rats Increases Food Intake but not Food Motivation
- 2020
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 28:8, s. 1503-1511
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Tidskriftsartikel (refereegranskat)abstract
- Objective The lateral parabrachial nucleus (lPBN) in the brainstem has emerged as a key area involved in feeding control that is targeted by several circulating anorexigenic hormones. Here, the objective was to determine whether the lPBN is also a relevant site for the orexigenic hormone ghrelin, inspired by studies in mice and rats showing that there is an abundance of ghrelin receptors in this area. Methods This study first explored whether iPBN cells respond to ghrelin involving Fos mapping and electrophysiological studies in rats. Next, rats were injected acutely with ghrelin, a ghrelin receptor antagonist, or vehicle into the lPBN to investigate feeding-linked behaviors. Results Curiously, ghrelin injection (intracerebroventricular or intravenous) increased Fos protein expression in the lPBN yet the predominant electrophysiological response was inhibitory. Intra-lPBN ghrelin injection increased chow or high-fat diet intake, whereas the antagonist decreased chow intake only. In a choice paradigm, intra-lPBN ghrelin increased intake of chow but not lard or sucrose. Intra-lPBN ghrelin did not alter progressive ratio lever pressing for sucrose or conditioned place preference for chocolate. Conclusions The lPBN is a novel locus from which ghrelin can alter consummatory behaviors (food intake and choice) but not appetitive behaviors (food reward and motivation).
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| 3. |
- Benedict, Christian, et al.
(författare)
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Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals
- 2016
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Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 5:12, s. 1175-1186
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Changes to the microbial community in the human gut have been proposed to promote metabolic disturbances that also occur after short periods of sleep loss (including insulin resistance). However, whether sleep loss affects the gut microbiota remains unknown. Methods: In a randomized within-subject crossover study utilizing a standardized in-lab protocol (with fixed meal times and exercise schedules), we studied nine normal-weight men at two occasions: after two nights of partial sleep deprivation (PSD; sleep opportunity 02: 45-07: 00 h), and after two nights of normal sleep (NS; sleep opportunity 22: 30-07: 00 h). Fecal samples were collected within 24 h before, and after two in-lab nights, of either NS or PSD. In addition, participants underwent an oral glucose tolerance test following each sleep intervention. Results: Microbiota composition analysis (V4 16S rRNA gene sequencing) revealed that after two days of PSD vs. after two days of NS, individuals exhibited an increased Firmicutes: Bacteroidetes ratio, higher abundances of the families Coriobacteriaceae and Erysipelotrichaceae, and lower abundance of Tenericutes (all P < 0.05) - previously all associated with metabolic perturbations in animal or human models. However, no PSD vs. NS effect on beta diversity or on fecal short-chain fatty acid concentrations was found. Fasting and postprandial insulin sensitivity decreased after PSD vs. NS (all P < 0.05). Discussion: Our findings demonstrate that short-term sleep loss induces subtle effects on human microbiota. To what extent the observed changes to the microbial community contribute to metabolic consequences of sleep loss warrants further investigations in larger and more prolonged sleep studies, to also assess how sleep loss impacts the microbiota in individuals who already are metabolically compromised. (C) 2016 The Author(s). Published by Elsevier GmbH.
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| 4. |
- Biermann, Frank, et al.
(författare)
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Transforming governance and institutions for global sustainability : key insights from the Earth System Governance Project
- 2012
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 4:1, s. 51-60
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Tidskriftsartikel (refereegranskat)abstract
- The current institutional framework for sustainable development is by far not strong enough to bring about the swift transformative progress that is needed. This article contends that incrementalism-the main approach since the 1972 Stockholm Conference-will not suffice to bring about societal change at the level and speed needed to mitigate and adapt to earth system transformation. Instead, the article argues that transformative structural change in global governance is needed, and that the 2012 United Nations Conference on Sustainable Development in Rio de Janeiro must turn into a major stepping stone for a much stronger institutional framework for sustainable development. The article details core areas where urgent action is required. The article is based on an extensive social science assessment conducted by 32 members of the lead faculty, scientific steering committee, and other affiliates of the Earth System Governance Project. This Project is a ten-year research initiative under the auspices of the International Human Dimensions Programme on Global Environmental Change (IHDP), which is sponsored by the International Council for Science (ICSU), the International Social Science Council (ISSC), and the United Nations University (UNU).
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| 5. |
- Brehony, Carina, et al.
(författare)
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Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development
- 2014
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Ingår i: Clinical and Vaccine Immunology. - : American Society for Microbiology. - 1556-6811 .- 1556-679X. ; 21:6, s. 847-853
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Tidskriftsartikel (refereegranskat)abstract
- New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and >= 25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.
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| 6. |
- Cedernaes, Jonathan, et al.
(författare)
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Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans
- 2018
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- Curtailed sleep promotes weight gain and loss of lean mass in humans, although the underlying molecular mechanisms are poorly understood. We investigated the genomic and physiological impact of acute sleep loss in peripheral tissues by obtaining adipose tissue and skeletal muscle after one night of sleep loss and after one full night of sleep. We find that acute sleep loss alters genome-wide DNA methylation in adipose tissue, and unbiased transcriptome-, protein-, and metabolite-level analyses also reveal highly tissue-specific changes that are partially reflected by altered metabolite levels in blood. We observe transcriptomic signatures of inflammation in both tissues following acute sleep loss, but changes involving the circadian clock are evident only in skeletal muscle, and we uncover molecular signatures suggestive of muscle breakdown that contrast with an anabolic adipose tissue signature. Our findings provide insight into how disruption of sleep and circadian rhythms may promote weight gain and sarcopenia.
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| 7. |
- Cedernaes, Jonathan, et al.
(författare)
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Short Sleep Makes Declarative Memories Vulnerable to Stress in Humans
- 2015
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 38:12, s. 1861-1868
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Tidskriftsartikel (refereegranskat)abstract
- Study Objective: This study sought to investigate the role of nocturnal sleep duration for the retrieval of oversleep consolidated memories, both prior to and after being cognitively stressed for similar to 30 minutes the next morning. Design: Participants learned object locations (declarative memory task comprising 15 card pairs) and a finger tapping sequence (procedural memory task comprising 5 digits) in the evening. After learning, participants either had a sleep opportunity of 8 hours (between similar to 23:00 and similar to 07:00, full sleep condition) or they could sleep between similar to 03:00 and similar to 07:00 (short sleep condition). Retrieval of both memory tasks was tested in the morning after each sleep condition, both before (similar to 08:30) and after being stressed (similar to 09:50). Setting: Sleep laboratory. Participants: 15 healthy young men. Results: The analyses demonstrated that oversleep memory changes did not differ between sleep conditions. However, in their short sleep condition, following stress hallmarked by increased subjective stress feelings, the men were unable to maintain their pre-stress performance on the declarative memory task, whereas their performance on the procedural memory task remained unchanged. While men felt comparably subjectively stressed by the stress intervention, overall no differences between pre- and post-stress recalls were observed following a full night of sleep. Conclusions: The findings suggest that 8-h sleep duration, within the range recommended by the US National Sleep Foundation, may not only help consolidate newly learned procedural and declarative memories, but also ensure full access to both during periods of subjective stress.
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| 8. |
- Chapman, Colin D., et al.
(författare)
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Acute sleep deprivation increases food purchasing in men
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 21:12
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate if acute sleep deprivation affects food purchasing choices in a mock supermarket. Design and Methods On the morning after one night of total sleep deprivation (TSD) or after one night of sleep, 14 normal-weight men were given a fixed budget (300 SEKapproximately 50 USD). They were instructed to purchase as much as they could out of a possible 40 items, including 20 high-caloric foods (>2 kcal/g) and 20 low-caloric foods (<2 kcal/g). The prices of the high-caloric foods were then varied (75%, 100% (reference price), and 125%) to determine if TSD affects the flexibility of food purchasing. Before the task, participants received a standardized breakfast, thereby minimizing the potential confound produced by hunger. In addition, morning plasma concentrations of the orexigenic hormone ghrelin were measured under fasting conditions. Results Independent of both type of food offered and price condition, sleep-deprived men purchased significantly more calories (+9%) and grams (+18%) of food than they did after one night of sleep (both P<0.05). Morning plasma ghrelin concentrations were also higher after TSD (P<0.05). However, this increase did not correlate with the effects of TSD on food purchasing. Conclusions This experiment demonstrates that acute sleep loss alters food purchasing behavior in men.
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| 9. |
- Fruhwürth, Stefanie, et al.
(författare)
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Novel Insights into How Overnutrition Disrupts the Hypothalamic Actions of Leptin.
- 2018
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Ingår i: Frontiers in endocrinology. - 1664-2392. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Obesity has become a worldwide health problem, but we still do not understand the molecular mechanisms that contribute to overeating and low expenditure of energy. Leptin has emerged as a major regulator of energy balance through its actions in the hypothalamus. Importantly, obese people exhibit high circulating levels of leptin, yet the hypothalamus no longer responds normally to this hormone to suppress appetite or to increase energy expenditure. Several well-known hypotheses have been proposed to explain impaired central responsiveness to the effects of leptin in obesity, including defective transit across the blood-brain barrier at the arcuate nucleus, hypothalamic endoplasmic reticulum stress, maladaptive sterile inflammation in the hypothalamus, and overexpression of molecules that may inhibit leptin signaling. We also discuss a new explanation that is based on our group's recent discovery of a signaling pathway that we named "NSAPP" after its five main protein components. The NSAPP pathway consists of an oxide transport chain that causes a transient, targeted burst in intracellular hydrogen peroxide (H2O2) to inactivate redox-sensitive members of the protein tyrosine phosphatase gene family. The NSAPP oxide transport chain is required for full activation of canonical leptin signaling in neurons but fails to function normally in states of overnutrition. Remarkably, leptin and insulin both require the NSAPP oxide transport chain, suggesting that a defect in this pathway could explain simultaneous resistance to the appetite-suppressing effects of both hormones in obesity.
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| 10. |
- Hansson, Caroline, 1981, et al.
(författare)
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Ghrelin Influences Novelty Seeking Behavior in Rodents and Men
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- Recent discoveries indicate an important role for ghrelin in drug and alcohol reward and an ability of ghrelin to regulate mesolimbic dopamine activity. The role of dopamine in novelty seeking, and the association between this trait and drug and alcohol abuse, led us to hypothesize that ghrelin may influence novelty seeking behavior. To test this possibility we applied several complementary rodent models of novelty seeking behavior, i.e. inescapable novelty-induced locomotor activity (NILA), novelty-induced place preference and novel object exploration, in rats subjected to acute ghrelin receptor (growth hormone secretagogue receptor; GHSR) stimulation or blockade. Furthermore we assessed the possible association between polymorphisms in the genes encoding ghrelin and GHSR and novelty seeking behavior in humans. The rodent studies indicate an important role for ghrelin in a wide range of novelty seeking behaviors. Ghrelin-injected rats exhibited a higher preference for a novel environment and increased novel object exploration. Conversely, those with GHSR blockade drastically reduced their preference for a novel environment and displayed decreased NILA. Importantly, the mesolimbic ventral tegmental area selective GHSR blockade was sufficient to reduce the NILA response indicating that the mesolimbic GHSRs might play an important role in the observed novelty responses. Moreover, in untreated animals, a striking positive correlation between NILA and sucrose reward behavior was detected. Two GHSR single nucleotide polymorphisms (SNPs), rs2948694 and rs495225, were significantly associated with the personality trait novelty seeking, as assessed using the Temperament and Character Inventory (TCI), in human subjects. This study provides the first evidence for a role of ghrelin in novelty seeking behavior in animals and humans, and also points to an association between food reward and novelty seeking in rodents. Citation: Hansson C, Shirazi RH, Naslund J, Vogel H, Neuber C, et al. (2012) Ghrelin Influences Novelty Seeking Behavior in Rodents and Men. PLoS ONE 7(12): e50409. doi:10.1371/journal.pone.0050409
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| 11. |
- Hogenkamp, Pleunie, et al.
(författare)
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Calorie anticipation alters food intake after low-caloric but not high-caloric preloads
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 21:8, s. 1548-1553
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Cognitive factors and anticipation are known to influence food intake. The current study examined the effect of anticipation and actual consumption of food on hormone (ghrelin, cortisol, insulin) and glucose levels, appetite and ad libitum intake, to assess whether changes in hormone levels might explain the predicted differences in subsequent food intake. Design and Methods: During four breakfast sessions, participants consumed a yogurt preload that was either low-caloric (LC; 180 kcal/300 g) or high-caloric (HC; 530 kcal/300 g), and were provided with either consistent or inconsistent calorie information (i.e. stating the caloric content of the preload was low or high). Appetite ratings and hormone and glucose levels were measured at baseline (t=0), after providing the calorie information about the preload (t=20), after consumption of the preload (t=40) and just before ad libitum intake (t=60). Results: Ad libitum intake was lower after HC preloads (as compared to LC preloads; p<0.01). Intake after LC preloads was higher when provided with (consistent) LC-information (467±254 kcal) as compared to (inconsistent) HC-information (346±210 kcal), but intake after the HC preloads did not depend on the information provided (LC-info: 290±178 kcal, HC-info: 333±179 kcal; caloric load*information p=0.03). Hormone levels did not respond in an anticipatory manner, and the post-prandial responses depended on actual calories consumed. Conclusions: These results suggest that both cognitive and physiological information determine food intake. When actual caloric intake was sufficient to produce physiological satiety, cognitive factors played no role; however, when physiological satiety was limited, cognitively-induced satiety reduced intake to comparable levels.
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| 12. |
- Hogenkamp, Pleunie S, et al.
(författare)
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Acute sleep deprivation increases portion size and affects food choice in young men.
- 2013
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 38:9, s. 1668-1674
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Tidskriftsartikel (refereegranskat)abstract
- Acute sleep loss increases food intake in adults. However, little is known about the influence of acute sleep loss on portion size choice, and whether this depends on both hunger state and the type of food (snack or meal item) offered to an individual. The aim of the current study was to compare portion size choice after a night of sleep and a period of nocturnal wakefulness (a condition experienced by night-shift workers, e.g. physicians and nurses). Sixteen men (age: 23±0.9 years, BMI: 23.6±0.6kg/m(2)) participated in a randomized within-subject design with two conditions, 8-h of sleep and total sleep deprivation (TSD). In the morning following sleep interventions, portion size, comprising meal and snack items, was measured using a computer-based task, in both fasted and sated state. In addition, hunger as well as plasma levels of ghrelin were measured. In the morning after TSD, subjects had increased plasma ghrelin levels (13%, p=0.04), and chose larger portions (14%, p=0.02), irrespective of the type of food, as compared to the sleep condition. Self-reported hunger was also enhanced (p<0.01). Following breakfast, sleep-deprived subjects chose larger portions of snacks (16%, p=0.02), whereas the selection of meal items did not differ between the sleep interventions (6%, p=0.13). Our results suggest that overeating in the morning after sleep loss is driven by both homeostatic and hedonic factors. Further, they show that portion size choice after sleep loss depend on both an individual's hunger status, and the type of food offered.
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| 13. |
- Hogenkamp, Pleunie S, et al.
(författare)
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Sweet taste perception not altered after acute sleep deprivation in healthy young men.
- 2013
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Ingår i: Somnologie : Schlafforschung und Schlafmedizin = Somnology : sleep research and sleep medicine. - : Springer Science and Business Media LLC. - 1432-9123 .- 1439-054X. ; 17:2, s. 111-114
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesized that acutely sleep-deprived participants would rate ascending concentrations of sucrose as more intense and pleasant, than they would do after one night of normal sleep. Such a finding would offer a potential mechanism through which acute sleep loss could promote overeating in humans.
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| 14. |
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| 15. |
- Ouni, Meriem, et al.
(författare)
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MiR-205 is up-regulated in islets of diabetes-susceptible mice and targets the diabetes gene Tcf7l2
- 2021
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 232:4
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Tidskriftsartikel (refereegranskat)abstract
- Aim: MicroRNAs play an important role in the maintenance of cellular functions by fine-tuning gene expression levels. The aim of the current study was to identify genetically caused changes in microRNA expression which associate with islet dysfunction in diabetic mice. Methods: To identify novel microRNAs involved in islet dysfunction, transcriptome and miRNome analyses were performed in islets of obese, diabetes-susceptible NZO and diabetes-resistant B6-ob/ob mice and results combined with quantitative trait loci (QTL) and functional in vitro analysis. Results: In islets of NZO and B6-ob/ob mice, 94 differentially expressed microRNAs were detected, of which 11 are located in diabetes QTL. Focusing on conserved microRNAs exhibiting the strongest expression difference and which have not been linked to islet function, miR-205-5p was selected for further analysis. According to transcriptome data and target prediction analyses, miR-205-5p affects genes involved in Wnt and calcium signalling as well as insulin secretion. Over-expression of miR-205-5p in the insulinoma cell line INS-1 increased insulin expression, left-shifted the glucose-dependence of insulin secretion and supressed the expression of the diabetes gene TCF7L2. The interaction between miR-205-5p and TCF7L2 was confirmed by luciferase reporter assay. Conclusion: MiR-205-5p was identified as relevant microRNA involved in islet dysfunction by interacting with TCF7L2.
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| 16. |
- Rabasa-Papio, Cristina, et al.
(författare)
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Behavioral consequences of exposure to a high fat diet during the post-weaning period in rats
- 2016
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Ingår i: Hormones and Behavior. - : Elsevier BV. - 0018-506X. ; 85, s. 56-66
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Tidskriftsartikel (refereegranskat)abstract
- We explored the impact of exposure to an obesogenic diet (High Fat-High Sucrose; HFS) during the post weaning period on sweet preference and behaviors linked to reward and anxiety. All rats were fed chow. In addition a HFS-transient group had access to this diet for 10 days from post-natal (PN) day 22 and a HFS-continuous group continued access until adult. Behavioral tests were conducted immediately after PN 32 (adolescence) or after PN 60 (adult) and included: the condition place preference (CPP) test for chocolate, sugar and saccharin preference (anhedonia), the elevated plus maze (anxiety-like behavior) and the locomotor response to quinpirole in the open field. Behavior was unaltered in adult rats in the HFS-transient group, suggesting that a short exposure to this obesogenic food does not induce long-term effects in food preferences, reward perception and value of palatable food, anxiety or locomotor activity. Nevertheless, rats that continued to have access to HFS ate less chocolate during CPP training and consumed less saccharin and sucrose when tested in adolescence, effects that were attenuated when these rats became adult. Moreover, behavioral effects linked to transient HFS exposure in adolescence were not sustained if the rats did not remain on that diet until adult. Collectively our data demonstrate that exposure to fat and sucrose in adolescence can induce immediate reward hypofunction after only 10 days on the diet. Moreover, this effect is attenuated when the diet is extended until the adult period, and completely reversed when the HFS diet is removed. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license.
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| 17. |
- Rabasa-Papio, Cristina, et al.
(författare)
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Divergent Metabolic Effects of Acute Versus Chronic Repeated Forced Swim Stress in the Rat
- 2019
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 27:3, s. 427-433
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study sought to examine divergence regarding the impact of acute versus chronic repeated stress on energy balance. Methods Rats were exposed to either chronic repeated forced swim (FS) stress for 7 days or an acute stress (a single FS). Body weight and food intake were measured daily. Metabolic parameters explored included brown adipose tissue (BAT) weight and activity. Results Chronic repeated FS stress decreased body weight and caloric efficiency. It also increased the relative weight of BAT. The same stressor delivered only once did not alter adrenal or BAT weight, but it did increase the metabolic activity of BAT. In stress-naive rats, acute FS stress induced an anorexigenic response during the first day after the stressor that caused a reduction in body weight (that persisted for 4 days). By contrast, the chronic FS rats did not show an anorexigenic response after the final stressor, and there was no change in body weight during the following 4 days. Conclusions Rats exposed to chronic repeated FS stress adapt to the stressor over time; they become less sensitive to its anorexigenic effects and its metabolic effects in BAT, adaptations that ultimately reduce sensitivity to the weight-lowering effects of an acute stressor.
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| 18. |
- Rask-Andersen, Mathias, et al.
(författare)
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Postprandial alterations in whole-blood DNA methylation are mediated by changes in white blood cell composition
- 2016
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 104:2, s. 518-525
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Tidskriftsartikel (refereegranskat)abstract
- Background: DNA methylation is an essential nuclear process associated with genomic functions such as transcription factor binding and the regulation of gene expression. DNA methylation patterns can also serve as potential biomarkers for disease progression and response to therapy. However, the full dynamics of DNA methylation across daily physiologic events have not been fully elucidated. Objective: We sought to study how ingesting a standardized meal acutely affects peripheral blood DNA methylation. Design: We performed an observational study in healthy men (n = 26) on DNA methylation and gene expression in whole blood before and 160 min after the ingestion of a standardized meal. Cytosine-phosphate-guanine (CpG) methylation was assayed on the HumanMethylation450k microarray, and gene expression was measured with the Human Gene 2.1 ST Array. Results: Differential methylation after food intake was detected in 13% of the analyzed probes (63,207 CpG probes) at a 5% false discovery rate (FDR). This effect was driven by changes in leukocyte fractions as estimated from comparisons against methylation datasets generated from sorted leukocytes. When methylation values were adjusted for estimated leukocyte fractions, 541 probes were observed to be altered in the postprandial state (5% FDR). Conclusions: Apparent alterations in DNA methylation 160 min after meal ingestion mainly reflect changes in the estimated leukocyte population in whole blood. These results have major methodologic implications for genome-wide methylation studies because they highlight the strong underlying effects of changes in leukocyte fractions on CpG methylation patterns as well as the potential importance of meal-standardized sampling procedures for future investigations when alterations in white blood cell fractions are unavailable.
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| 19. |
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| 20. |
- Shirazi, Rozita H., et al.
(författare)
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Glucagon-like peptide 1 receptor induced suppression of food intake, and body weight is mediated by central IL-1 and IL-6
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 110:40, s. 16199-16204
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide 1 (GLP-1), produced in the intestine and the brain, can stimulate insulin secretion from the pancreas and alleviate type 2 diabetes. The cytokine interleukin-6 (IL-6) may enhance insulin secretion from beta-cells by stimulating peripheral GLP-1 production. GLP-1 and its analogs also reduce food intake and body weight, clinically beneficial actions that are likely exerted at the level of the CNS, but otherwise are poorly understood. The cytokines IL-6 and interleukin 1 beta (IL-1 beta) may exert an anti-obesity effect in the CNS during health. Here we found that central injection of a clinically used GLP-1 receptor agonist, exendin-4, potently increased the expression of IL-6 in the hypothalamus (11-fold) and the hindbrain (4-fold) and of IL-1 beta in the hypothalamus, without changing the expression of other inflammation-associated genes. Furthermore, hypothalamic and hindbrain interleukin-associated intracellular signals [phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and suppressor of cytokine signaling-1 (SOCS1)] were also elevated by exendin-4. Pharmacologic disruption of CNS IL-1 receptor or IL-6 biological activity attenuated anorexia and body weight loss induced by central exendin-4 administration in a rat. Simultaneous blockade of IL-1 and IL-6 activity led to a more potent attenuation of exendin-4 effects on food intake. Mice with global IL-1 receptor gene knockout or central IL-6 receptor knockdown showed attenuated decrease in food intake and body weight in response to peripheral exendin-4 treatment. GLP-1 receptor activation in the mouse neuronal Neuro2A cell line also resulted in increased IL-6 expression. These data outline a previously unidentified role of the central IL-1 and IL-6 in mediating the anorexic and body weight loss effects of GLP-1 receptor activation.
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| 21. |
- Skibicka, Karolina P, et al.
(författare)
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Divergent circuitry underlying food reward and intake effects of ghrelin: Dopaminergic VTA-accumbens projection mediates ghrelin's effect on food reward but not food intake.
- 2013
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Ingår i: Neuropharmacology. - : Elsevier BV. - 1873-7064 .- 0028-3908. ; 73, s. 274-283
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Tidskriftsartikel (refereegranskat)abstract
- Obesity has reached global epidemic proportions and creating an urgent need to understand mechanisms underlying excessive and uncontrolled food intake. Ghrelin, the only known circulating orexigenic hormone, potently increases food reward behavior. The neurochemical circuitry that links ghrelin to the mesolimbic reward system and to the increased food reward behavior remains unclear. Here we examine whether VTA-NAc dopaminergic signaling is required for the effects of ghrelin on food reward and intake. In addition, we examine the possibility of endogenous ghrelin acting on the VTA-NAc dopamine neurons. A D1-like or a D2 receptor antagonist was injected into the NAc in combination with ghrelin microinjection into the VTA to investigate whether this blockade attenuates ghrelin-induced food reward behavior. VTA injections of ghrelin produced a significant increase in food motivation/reward behavior, as measured by sucrose-induced progressive ratio operant conditioning, and chow intake. Pretreatment with either a D1-like or D2 receptor antagonist into the NAc, completely blocked the reward effect of ghrelin, leaving chow intake intact. We also found that this circuit is potentially relevant for the effects of endogenously released ghrelin as both antagonists reduced fasting (a state of high circulating levels of ghrelin) elevated sucrose-motivated behavior but not chow hyperphagia. Taken together our data identify the VTA to NAc dopaminergic projections, along with D1-like and D2 receptors in the NAc, as essential elements of the ghrelin responsive circuits controlling food reward behavior. Interestingly results also suggest that food reward behavior and simple intake of chow are controlled by divergent circuitry, where NAc dopamine plays an important role in food reward but not in food intake.
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| 22. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 23. |
- Taha, Muhamed-Kheir, et al.
(författare)
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Defining the breakpoint for resistance to rifampicin in Neisseria meningitidis by rpoB sequencing
- 2009
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Clinical isolates of Neisseria meningitidis resistant to rifampicin are important to identify asthey lead to failure of chemoprophylaxis of meningococcal disease. However, theidentification of these isolates is hindered by the absence of a harmonized breakpoint despiteefforts of standardization. In the present study, a large number (n=352) of clinical N.meningitidis isolates from 12 mainly European countries and spanning over 25 years (1984 to2009) were examined. The collection comprised all clinical isolates with MIC 0.25 mg/lreceived by the national reference laboratories for meningococci in the participating countries(n=161). In addition, representative isolates displaying MIC of rifampicin <0.25 mg/l wereexamined (n=191). Phenotyping and genotyping of isolates were performed and a 660 bpDNA fragment of the rpoB gene was sequenced in all the included isolates. Sequencesdiffering by at least one nucleotide were defined as a unique rpoB allele (n=55). Geometricmeans of MIC were calculated for isolates displaying the same allele. All the clinical isolatesdisplaying MIC >1 mg/l of rifampicin possessed rpoB alleles with critical mutations (in total21 alleles), resulting in substitutions at the codon H552 and less frequently at nearby codons(S548 and S557). These alterations were absent in the alleles (n=34) found in all isolates withMIC 1 mg/l. Based on these findings, rifampicin susceptible isolates could be defined asthose with MIC 1 mg/l. A new web site was created based on the data from this work (http://neisseria.org/nm/typing/rpoB). The rifampicin resistant isolates belonged to diversegenetic lineages and provoked lower bacteremia levels in mice. This biological cost mayexplain the non-expansion of the rifampicin resistant isolates.
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| 24. |
- van Egmond, Lieve T, et al.
(författare)
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Effects of acute sleep loss on leptin, ghrelin, and adiponectin in adults with healthy weight and obesity : A laboratory study
- 2023
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Ingår i: Obesity. - : John Wiley & Sons. - 1930-7381 .- 1930-739X. ; 31:3, s. 635-641
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study investigated whether blood concentrations of leptin, ghrelin, and adiponectin are affected by acute total sleep deprivation in a sex- and weight-specific manner.METHODS: A total of 44 participants (mean age 24.9 years; 20 women; 19 with obesity) participated in a crossover design, including one night of sleep deprivation and one night of sleep in the laboratory. After each night, fasting blood was collected.RESULTS: After sleep deprivation, fasting levels of leptin were lower (mean [SE], vs. sleep: 17.3 [2.6] vs. 18.6 [2.8] ng/mL), whereas those of ghrelin and adiponectin were higher (839.4 [77.5] vs. 741.4 [63.2] pg/mL and 7.5 [0.6] vs. 6.8 [0.6] μg/mL, respectively; all p < 0.05). The changes in leptin and adiponectin following sleep loss were more pronounced among women. Furthermore, the ghrelin increase was stronger among those with obesity after sleep loss. Finally, the sleep loss-induced increase in adiponectin was more marked among normal-weight participants.CONCLUSIONS: Acute sleep deprivation reduces blood concentrations of the satiety hormone leptin. With increased blood concentrations of ghrelin and adiponectin, such endocrine changes may facilitate weight gain if persisting over extended periods of sleep loss. The observed sex- and weight-specific differences in leptin, ghrelin, and adiponectin call for further investigation.
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| 25. |
- Vogel, Heike, et al.
(författare)
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Genetic predisposition to obesity affects behavioural traits including food reward and anxiety-like behaviour in rats
- 2017
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328. ; 328, s. 95-104
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Tidskriftsartikel (refereegranskat)abstract
- Here we sought to define behavioural traits linked to anxiety, reward, and exploration in different strains of rats commonly used in obesity research. We hypothesized that genetic variance may contribute not only to their metabolic phenotype (that is well documented) but also to the expression of these behavioural traits. Rat strains that differ in their susceptibility to develop an obese phenotype (Sprague-Dawley, Obese Prone, Obese Resistant, and Zucker rats) were exposed to a number of behavioural tests starting at the age of 8 weeks. We found a similar phenotype in the obesity susceptible models, Obese Prone and Zucker rats, with a lower locomotor activity, exploratory activity, and higher level of anxiety like behaviour in comparison to the leaner Obese Resistant strain. We did not find evidence that rat strains with a genetic predisposition to obesity differed in their ability to experience reward from chocolate (in a condition place preference task). However, Zucker rats show higher motivated behaviour for sucrose compared to Obese Resistant rats when the effort required to obtain palatable food is relatively low. Together our data demonstrate that rat strains that differ in their genetic predisposition to develop obesity also differ in their performance in behavioural tests linked to anxiety, exploration, and reward and that these differences are independent of body weight. We conclude that genetic variations which determine body weight and the aforementioned behaviours co-exist but that future studies are required to identify whether (and which) common genes are involved. (C) 2017 The Authors. Published by Elsevier B.V.
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| 26. |
- Vogel, Heike, et al.
(författare)
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GLP-1 and estrogen conjugate acts in the supramammillary nucleus to reduce food-reward and body weight
- 2016
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Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 110, s. 396-406
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Tidskriftsartikel (refereegranskat)abstract
- The obesity epidemic continues unabated and currently available pharmacological treatments are not sufficiently effective. Combining gut/brain peptide, GLP-1, with estrogen into a conjugate may represent a novel, safe and potent, strategy to treat diabesity. Here we demonstrate that the central administration of GLP-1-estrogen conjugate reduced food reward, food intake, and body weight in rats. In order to determine the brain location of the interaction of GLP-1 with estrogen, we avail of single-photon emission computed tomography imaging of regional cerebral blood flow and pinpoint a brain site unexplored for its role in feeding and reward, the supramammillary nucleus (SUM) as a potential target of the conjugated GLP-1-estrogen. We confirm that conjugated GLP-1 and estrogen directly target the SUM with site-specific microinjections. Additional microinjections of GLP-1-estrogen into classic energy balance controlling nuclei, the lateral hypothalamus (LH) and the nucleus of the solitary tract (NTS) revealed that the metabolic benefits resulting from GLP-1-estrogen injections are mediated through the LH and to some extent by the NTS. In contrast, no additional benefit of the conjugate was noted on food reward when the compound was microinjected into the LH or the NTS, identifying the SUM as the only neural substrate identified here to underlie the reward reducing benefits of GLP-1 and estrogen conjugate. Collectively we discover a surprising neural substrate underlying food intake and reward effects of GLP-1 and estrogen and uncover a new brain area capable of regulating energy balance and reward. © 2016 The Author(s)
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| 27. |
- Willerton, Laura, et al.
(författare)
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Geographically widespread invasive meningococcal disease caused by a ciprofloxacin resistant non-groupable strain of the ST-175 clonal complex
- 2020
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Ingår i: Journal of Infection. - : W. B. Saunders Company. - 0163-4453 .- 1532-2742. ; 81:4, s. 575-584
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Invasive meningococcal disease (IMD) caused by non-serogroupable (NG) strains mainly affects immunocompromised individuals. Reduced susceptibility to penicillin in meningococci is increasing in Europe but ciprofloxacin resistance remains rare. In 2019, three travel-related meningococcal disease cases caused by a ciprofloxacin-resistant NG strain were identified in England, leading Germany to report four additional IMD cases (2016 to 2019). We describe these and newly identified cases and characterise the strain responsible.METHODS: Cases were identified as part of national surveillance and by analysing available genomes using PubMLST tools.RESULTS: Of the cases identified in England in 2019, two geographically distinct cases developed conjunctivitis after returning from Mecca (Kingdom of Saudi Arabia) and a third linked case presented with IMD. Of the four cases from Germany, three occurred in asylum seekers - two familial and a further geographically distinct case. Further IMD cases were identified in Italy (n=2; 2017-2018), Sweden (n=1; 2016) and England (n=1; 2015). A single ST-175 clonal complex (cc175) strain with genosubtype P1.22-11,15-25 was responsible. Decreased susceptibility to penicillin was widespread with three ciprofloxacin resistant subclusters. Constituent isolates were potentially covered by subcapsular vaccines.CONCLUSION: This disease associated NG cc175 strain exhibits resistance to antibiotics commonly used to prevent IMD but is potentially covered by subcapsular (meningococcal B) vaccines.
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