A5079001303- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Biochemical Analysis and Sensing Techniques
- Diet and metabolism studies
- Neuropeptides and Animal Physiology
- Neurotransmitter Receptor Influence on Behavior
- Forensic Toxicology and Drug Analysis
- Schizophrenia research and treatment
- Psychedelics and Drug Studies
- Diabetes Treatment and Management
- Photoreceptor and optogenetics research
- Light effects on plants
- Genetic Neurodegenerative Diseases
- Photochemistry and Electron Transfer Studies
- Sirtuins and Resveratrol in Medicine
- Protein Hydrolysis and Bioactive Peptides
- Electroconvulsive Therapy Studies
- Photochromic and Fluorescence Chemistry
- Receptor Mechanisms and Signaling
- Lipid metabolism and biosynthesis
- Neurobiology and Insect Physiology Research
- Eating Disorders and Behaviors
- Porphyrin and Phthalocyanine Chemistry
- Poisoning and overdose treatments
University of Copenhagen
2014-2024
Novo Nordisk Foundation
2015-2024
Laboratory of Molecular Genetics
2016
Novo Nordisk Foundation Center for Basic Metabolic Research
2015
Neurotensin (NT) is a peptide expressed in the brain and gastrointestinal tract. Brain NT inhibits food intake, but effects of peripheral are less investigated. In this study, decreased intake both mice rats, which was abolished by antagonist. Using c-Fos immunohistochemistry, we found that activated brainstem hypothalamic regions. The anorexigenic effect preserved vagotomized lasted shorter than sham-operated mice. This combination with strong increase activation area postrema after ip...
Background:Besides the well-known effects of ghrelin on adiposity and food intake regulation, system has been shown to regulate aspects behavior including anxiety stress. However, effect virus-mediated overexpression receptor in amygdala not previously addressed directly.
Significance Obesity is a major health threat of the twenty-first century, impacting individual patients and healthcare expenditure. Due to safety concerns, few antiobesity treatments with only moderate effect remain on market. The ghrelin receptor an attractive target for development novel drugs, since increases both fat accumulation food intake. However, also modulates variety additional physiological functions. Thus, drugs targeting may induce unacceptable side effects have limited...
Neurotensin (NT), a gut hormone and neuropeptide, increases in circulation after bariatric surgery rodents humans inhibits food intake mice. However, its potential to treat obesity the subsequent metabolic dysfunctions have been difficult assess owing short half-life vivo. Here, we demonstrate that long-acting, pegylated analog of NT peptide (P-NT) reduces intake, body weight, adiposity diet-induced obese mice when administered once daily for 6 days. Strikingly, P-NT was combined with...
Liver-expressed antimicrobial peptide-2 (LEAP2) is an endogenous ghrelin receptor antagonist, which upregulated in the fed state and downregulated during fasting. We hypothesized that ketone body beta-hydroxybutyrate (BHB) involved downregulation of LEAP2 conditions with high circulating levels BHB.Hepatic intestinal Leap2 expression were determined 3 groups mice increasing BHB: prolonged fasting, ketogenic diet, oral BHB treatment. measured lean obese individuals, human individuals...
Neurons in the arcuate nucleus of hypothalamus are involved regulation food intake and energy expenditure, dysregulation signalling these neurons promotes development obesity. The role rate-limiting enzyme NAD+ salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT), for homeostasis by has not been extensively studied.We determined whether Nampt mRNA or protein levels mice were affected diet-induced obesity, fasting re-feeding, leptin ghrelin treatment. Primary hypothalamic treated...
Brain tissue is a useful alternative to blood in postmortem forensic investigations, but scarcity of information on reference concentrations brain makes interpretation challenging. Here we present study 43 cases where the antipsychotic drug quetiapine was quantified and related blood. For cases, unrelated cause death (N = 36), 10-90 percentiles for were 0.030-1.54 mg/kg (median 0.48 mg/kg, mean 0.79 mg/kg). Corresponding percentile values 0.007-0.39 0.15 0.19 mg/kg), giving brain-blood ratio...
To characterize mechanisms responsible for fat accumulation we used a selectively bred obesity-prone (OP) and obesity-resistant (OR) rat model where the rats were fed Western diet 76 days. Body composition was assessed by magnetic resonance imaging scans, as expected, OP developed higher degree of compared with OR rats. Indirect calorimetry showed that had respiratory exchange ratio (RER) rats, indicating an impaired ability to oxidize fat. The lower expression carnitine palmitoyltransferase...
The goal of this study was to investigate the importance central hormone-sensitive lipase (HSL) expression in regulation food intake and body weight mice clarify whether intracellular lipolysis mammalian hypothalamus plays a role regulating appetite. Using pharmacological genetic approaches, we investigated HSL rodent brain feeding energy homeostasis under basal conditions during acute stress high-fat diet feeding. We found that HSL, key enzyme catabolism cellular lipid stores, is expressed...
Postmortem femoral blood concentrations of the antipsychotic drugs aripiprazole, chlorprothixene and its metabolite, quetiapine were determined by LC-MS-MS in 25 cases for aripiprazole 60 each quetiapine. For where cause death was not related to considered drugs, following concentration intervals (10-90 percentiles) observed: 0.049-0.69 mg/kg 0.006-0.24 chlorprothixene, 0.006-0.37 These ranges largely correspond therapeutic plasma levels observed vivo suggesting no or only limited postmortem...
Ghrelin receptor (Ghr-R) signaling in neurons of the ventral tegmental area (VTA) can modulate dopaminergic function and reward-related effects both palatable foods drugs abuse. In this study, we re-introduced Ghr-R VTA knockout mice (Ghr-RVTA mice) to specifically study importance constitutively active for neuronal signaling. Our results showed that re-introduction had no impact on body weight or food intake under basal conditions. However, during novel environment stress Ghr-RVTA increased...
Obesity is a complex disease associated with high risk of comorbidities. Gastric bypass surgery, an invasive procedure low patient eligibility, currently the most effective intervention that achieves sustained weight loss. This beneficial effect attributed to alterations in gut hormone signaling. An attractive alternative pharmacologically mimic effects bariatric surgery by targeting several hormonal axes. The G protein-coupled receptor 39 (GPR39) expressed gastrointestinal tract has been...
Abstract Huntington's disease ( HD ) is a heritable neurodegenerative disorder, characterised by metabolic disturbances, along with cognitive and psychiatric impairments. Targeting dysfunction via the maintenance of body weight fat mass restoration peripheral energy metabolism can improve progression neurological symptoms. In this respect, we focused on therapeutic potential orexigenic peptide hormone ghrelin, which plays an important role in promoting positive balance. present study, found...
Abstract Dopamine‐producing tyrosine hydroxylase ( TH ) neurones in the hypothalamic arcuate nucleus ARC have recently been shown to be involved ghrelin signalling and body weight homeostasis. In present study, we investigate role of intracellular regulator RhoA response peripheral hormones. Diet‐induced obesity was found associated with increased phosphorylation , indicating obesity‐associated activity neurones. Mice which specifically knocked out ‐RhoA −/− mice) were more sensitive...
A model system of the flavin chromophore was synthesized and investigated for its intrinsic optical properties by gas phase action spectroscopy using an ion storage ring. An ammonium group anchored to this allow transfer electrospray ionization studying influence hydrogen bonding a nearby positive charge. According calculations one atoms favorably forms intramolecular ionic bond oxygen chromophore, interaction found cause blueshift S0 → S1 transition redshift S2 transition. For comparison,...
A new procedure for functionalization of the dihydroazulene photoswitch on its seven-membered ring was developed, which has allowed isolation first with a phenyl substituent at position 5 from mixture regioisomers. Light-induced ring-opening to corresponding vinylheptafulvene and thermal back-reaction studied in detail.
Midbrain dopaminergic neurons (DANs) are subject to extensive metabotropic regulation, but the repertoire of G protein-coupled receptors (GPCRs) present in these has not been mapped. Here, we isolate DANs from Dat-eGFP mice generate a GPCR atlas by unbiased qPCR array expression analysis 377 GPCRs. Combined with data mining scRNA-seq databases, identify multiple DAN subpopulations 38 representing majority transcripts. We 41 expressed midbrain non-DAN cells, including free fatty acid receptor...