A5075307766- Adipose Tissue and Metabolism
- Sirtuins and Resveratrol in Medicine
- Pancreatic function and diabetes
- Autophagy in Disease and Therapy
- Diet and metabolism studies
- PARP inhibition in cancer therapy
- Diet, Metabolism, and Disease
- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- Liver Disease Diagnosis and Treatment
- Celiac Disease Research and Management
- Diabetes and associated disorders
- Genetic Neurodegenerative Diseases
- Dietary Effects on Health
- Circadian rhythm and melatonin
- scientometrics and bibliometrics research
- Metabolism, Diabetes, and Cancer
- Health and Medical Research Impacts
- Neurobiology and Insect Physiology Research
- Allergic Rhinitis and Sensitization
- Congenital Diaphragmatic Hernia Studies
- Contact Dermatitis and Allergies
- Academic Publishing and Open Access
- MicroRNA in disease regulation
- FOXO transcription factor regulation
Novo Nordisk Foundation
2016-2025
Novo Nordisk Foundation Center for Basic Metabolic Research
2025
University of Copenhagen
2015-2024
Rigshospitalet
2013-2014
BioInnovation Institute
2014
The ribotoxic stress response (RSR) is a signaling pathway in which the p38- and c-Jun N-terminal kinase (JNK)-activating mitogen-activated protein (MAP3K) ZAKα senses stalling and/or collision of ribosomes. Here, we show that reactive oxygen species (ROS)-generating agents trigger ribosomal impairment activation. Conversely, zebrafish larvae deficient for are protected from ROS-induced pathology. Livers mice fed ROS-generating diet exhibit ZAKα-activating changes elongation dynamics....
Glucagon is well known to regulate blood glucose but may be equally important for amino acid metabolism. Plasma levels of acids are regulated by glucagon-dependent mechanism(s), while stimulate glucagon secretion from alpha cells, completing the recently described liver-alpha cell axis. The mechanisms underlying cycle and possible impact hepatic steatosis unclear. We assessed clearance in vivo mice treated with a receptor antagonist (GRA), transgenic 95% reduction steatosis. In addition, we...
The ability of adipose tissue to expand and contract in response fluctuations nutrient availability is essential for the maintenance whole-body metabolic homeostasis. Given scarcity that mammals faced millions years, programs involved this plasticity were likely evolved be highly efficient promoting lipid storage. Ironically, previously advantageous feature may now represent a liability given caloric excess modern society. We speculate nicotinamide adenine dinucleotide (NAD+) biosynthesis...
NAD+ is a co-factor and substrate for enzymes maintaining energy homeostasis. Nicotinamide phosphoribosyltransferase (NAMPT) controls synthesis, in skeletal muscle, essential muscle integrity. However, the underlying molecular mechanisms by which synthesis affects health remain poorly understood. Thus, objective of current study was to delineate role NAMPT-mediated biosynthesis development function. To determine Nampt function, we generated muscle-specific KO (SMNKO) mice. We performed...
Dietary restriction (DR) reduces adiposity and improves metabolism in patients with one or more symptoms of metabolic syndrome. Nonetheless, it remains elusive whether the benefits DR humans are mediated by calorie nutrient restriction. This study was conducted to determine isocaloric dietary protein is sufficient confer beneficial effects We performed a prospective, randomized controlled intervention under constant nutritional medical supervision. Twenty-one individuals diagnosed syndrome...
Except for latitudes close to the equator, seasonal variation in light hours can change dramatically between summer and winter. Yet investigations into interplay energy metabolism circadian rhythms typically use a 12 h light:12 dark photoperiod corresponding duration at equator. We hypothesized that altering affects both rhythmicity of peripheral tissue clocks homeostasis. Mice were housed photoperiods representing either summer, winter, or equinox. winter exhibited an increase amplitude...
Molecular clocks in the periphery coordinate tissue-specific daily biorhythms by integrating input from hypothalamic master clock and intracellular metabolic signals. One such key signal is cellular concentration of NAD + , which oscillates along with its biosynthetic enzyme, nicotinamide phosphoribosyltransferase (NAMPT). levels feed back into to influence rhythmicity biological functions, yet whether this fine-tuning occurs ubiquitously across cell types a core feature unknown. Here, we...
SBI-0206965, originally identified as an inhibitor of the autophagy initiator kinase ULK1, has recently been reported a more potent and selective AMP-activated protein (AMPK) relative to widely used, but promiscuous Compound C/Dorsomorphin. Here, we studied effects SBI-0206965 on AMPK signalling metabolic readouts in multiple cell types, including hepatocytes, skeletal muscle cells adipocytes. We observed dose dependently attenuated activator (991)-stimulated ACC phosphorylation inhibition...
Nicotinamide adenine dinucleotide (NAD + ) can be synthesized by nicotinamide phosphoribosyltransferase (NAMPT). We aimed to determine the role of NAMPT in maintaining NAD levels, mitochondrial function, and metabolic homeostasis skeletal muscle cells. generated stable Nampt knockdown (sh KD) C2C12 cells using a shRNA lentiviral approach. Moreover, we applied gene electrotransfer express Cre recombinase tibialis anterior floxed mice. In sh KD myoblasts, levels were reduced 70% 50%,...
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...
Dietary gluten influences the development of type 1 diabetes in nonobese diabetic (NOD) mice and biobreeding rats, has been shown to influence a wide range immunological factors pancreas gut. In present study, effects on NK cells were studied vitro vivo. We demonstrated that gliadin increased direct cytotoxicity IFN-γ secretion from murine splenocytes toward pancreatic beta-cell line MIN6 cells. Additionally, stimulation led significantly proportion degranulating C57BL/6 CD107a(+)...
Nicotinamide phosphoribosyltransferase (NAMPT) converts nicotinamide to NAD+. As low hepatic NAD+ levels have been linked the development of nonalcoholic fatty liver disease, we hypothesized that ablation Nampt would affect susceptibility injury in response diet-induced metabolic stress. Following 3 weeks on a low-methionine and choline-free 60% high-fat diet, hepatocyte-specific knockout (HNKO) mice accumulated less triglyceride than WT littermates but had increased histological scores for...
Blood glucose is one of the most essential parameters in metabolic research. Yet, accurate blood monitoring mouse models diabetes challenging due to significant stress associated with measurements and variability development among experimental models. This necessitates frequent measurements, which only provide intermittent data may not accurately reflect continuous changes. To address these issues, we have utilized Tecniplast DVC system monitor bedding moisture, enabling detection increased...
Abstract Cells change their metabolic profiles in response to underlying gene regulatory networks, but how can alterations metabolism encode specific transcriptional instructions? Here, we show that forcing a embryonic stem cells (ESCs) promotes developmental identity better approximates the inner cell mass (ICM) of early mammalian blastocyst cultures. This shift cellular depends on inhibition glycolysis and stimulation oxidative phosphorylation (OXPHOS) triggered by replacement d -glucose...
In non-obese diabetic (NOD) mice, diabetes incidence is reduced by a gluten-free diet. Gluten peptides, such as the compound gliadin, can cross intestinal barrier and may directly affect pancreatic beta cells. We investigated effects of enzymatically-digested gliadin in NOD INS-1E cells rat islets. Six injections digest 6-week-old mice did not development, but increased weight gain (20% increase day 100). cells, incubation with induced dose-dependent insulin secretion, up to 2.5-fold after...
Adipose tissue regulates whole-body energy balance and is crucial for metabolic health. With surplus, adipose expands, which may lead to local areas of hypoxia inflammation, consequently impair insulin sensitivity. We report that DICER, a key enzyme miRNA maturation, significantly lower in abdominal subcutaneous white men with obesity compared lean phenotype. Furthermore, DICER profoundly downregulated mouse liver within the first week on high-fat diet (HFD), remains low after prolonged HFD...
<h3>Background</h3> Sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase, with a key role in the regulation of numerous metabolic pathways. Of special relevance to Huntington’s disease (HD), SIRT1 deacetylates and activates peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Furthermore, acts as positive regulator brain-derived neurotrophic factor (BDNF) expression through stimulation CREB-TORC1 transcription complex. Both PGC-1α activity BDNF are reduced HD models,...