A5021672623- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Lipid metabolism and biosynthesis
- Metabolism, Diabetes, and Cancer
- Cellular Mechanics and Interactions
- Diet and metabolism studies
- Diet, Metabolism, and Disease
- Growth Hormone and Insulin-like Growth Factors
- Diabetes and associated disorders
- Muscle Physiology and Disorders
- Lipid metabolism and disorders
- Adrenal Hormones and Disorders
- Sirtuins and Resveratrol in Medicine
- Ubiquitin and proteasome pathways
- Muscle metabolism and nutrition
- Graphene and Nanomaterials Applications
- Gut microbiota and health
- Diabetes Management and Research
- Adipokines, Inflammation, and Metabolic Diseases
- Liver Disease Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Vitamin D Research Studies
- Cardiac Ischemia and Reperfusion
- Genetic Associations and Epidemiology
- Research in Cotton Cultivation
Novo Nordisk Foundation
2014-2024
University of Copenhagen
2014-2024
Aarhus University
2012-2021
University of Birmingham
2020
Aarhus University Hospital
2009-2016
Aging decreases skeletal muscle mass and strength, but aerobic resistance exercise training maintains function. NAD+ is a coenzyme for ATP production required substrate enzymes regulating cellular homeostasis. In muscle, mainly generated by the salvage pathway in which nicotinamide phosphoribosyltransferase (NAMPT) rate-limiting. NAMPT with age human increases levels young men. However, whether distinct modes of increase both old people unknown. We assessed effects 12 weeks on abundance...
The combination of decreasing food intake and increasing energy expenditure represents a powerful strategy for counteracting cardiometabolic diseases such as obesity type 2 diabetes1. Yet current pharmacological approaches require conjugation multiple receptor agonists to achieve both effects2–4, so far, no safe energy-expending option has reached the clinic. Here we show that activation neurokinin (NK2R) is sufficient suppress appetite centrally increase peripherally. We focused on NK2R...
Aims Subgroups of patients with type 2 diabetes mellitus demand large insulin doses to maintain euglycemia. These are characterized by severe skeletal muscle resistance and the underlying pathology remains unclear. The purpose this study was examine protein expression principal glucose transporter, GLUT4, associated proteins in from diabetic resistance. Methods Seven (mean dose 195 IU/day) were compared seven age matched who did not require treatment, an healthy control group. Protein GLUT4...
Given that cellular O-GlcNAcylation levels are thought to be real-time measures of nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role transferase (OGT), enzyme mediates O-GlcNAcylation, in skeletal muscle. We assessed muscle from obese, type 2 diabetic people, characterized muscle-specific OGT knockout (mKO) mice metabolic cages measured energy expenditure substrate utilization pattern using indirect calorimetry. Whole body...
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...
Fasting and exercise are characterized by increased lipolysis, but the underlying mechanisms not fully understood.The study was designed to test whether fasting affect mRNA protein levels of adipose triglyceride lipase (ATGL) G(0)/G(1) switch gene 2 (G0S2), a recently discovered ATGL inhibitor, in humans.We studied eight healthy men (age, 25.5 ± 4.3 yr) for 6 h (a 4-h basal 2-h clamp period) on three occasions randomized crossover design: 1) state after; 2) 72-h fasting; 3) 1-h (65%...
During fasting, human skeletal muscle depends on lipid oxidation for its energy substrate metabolism. This is associated with the development of insulin resistance and a subsequent reduction insulin-stimulated glucose uptake. The underlying mechanisms controlling action under these conditions are unresolved. In randomized design, we investigated eight healthy subjects after 72-h fast compared 10-h overnight fast. Insulin was assessed by hyperinsulinemic euglycemic clamp determining signaling...
Background Lipolysis is accelerated during the acute phase of inflammation, a process being regulated by pro-inflammatory cytokines (e.g. TNF-α), stress-hormones, and insulin. The intracellular mechanisms remain elusive we therefore measured pro- anti-lipolytic signaling pathways in adipocytes after vivo endotoxin exposure. Methods Eight healthy, lean, male subjects were investigated using randomized cross over trial with two interventions: i) bolus injection saline (Placebo) ii)...
The lipolytic effects of growth hormone (GH) have been known for half a century and play an important physiological role substrate metabolism during fasting. In addition, sustained GH-induced lipolysis is causally linked to insulin resistance. However, the underlying molecular mechanisms remain elusive. present study, we obtained experimental data in human subjects used adipose-derived stromal vascular cells (hADSCs) as model system elucidate GH-triggered signaling that stimulates adipose...
Insulin resistance induced by growth hormone (GH) is linked to promotion of lipolysis unknown mechanisms. We hypothesized that suppression the activity pyruvate dehydrogenase in active form (PDHa) underlies GH-induced insulin similar what observed during fasting.Eight healthy male subjects were studied four times a randomized, single-blinded parallel design: Control, GH, Fasting (36 h) and GH + Fasting. (30 ng × kg(-1) min(-1)) or saline was infused throughout metabolic study day. Substrate...
Increased availability of lipids may conserve muscle protein during catabolic stress. Our study was designed to define 1) intracellular mechanisms leading increased lipolysis and 2) whether this scenario is associated with decreased amino acid urea fluxes, release in obese subjects under basal fasting conditions. We therefore studied nine lean twice, after 12 72 h fasting, using measurements mRNA expression phosphorylation lipolytic metabolic signaling molecules fat together whole body...
Significance Aerobic exercise elicits an integrated metabolic response that involves multiple tissues and confers beneficial effects to health. Here we found this integrative energy-sensing pathways in muscle fat circulating factors lead the upregulation of type III endoribonuclease DICER adipose tissue consequent increase microRNAs. Upon upregulation, microRNA-203-3p inhibit glucose utilization by cells favor oxidative metabolism. In turn, supports exercised with adequate substrate...
Omega-3 fatty acids from fish oil reduce triglyceride levels in mammals, yet the mechanisms underlying this effect have not been fully clarified, despite clinical use of omega-3 ethyl esters to treat severe hypertriglyceridemia and cardiovascular disease risk humans. Here, we identified bile a class hypotriglyceridemic acid–derived N-acyl taurines (NATs) that, after dietary acid supplementation, increased concentrations similar those steroidal acids. The biliary docosahexaenoic...
Abstract The gut microbiota impacts systemic levels of multiple metabolites including NAD + precursors through diverse pathways. Nicotinamide riboside (NR) is an precursor capable regulating mammalian cellular metabolism. Some bacterial families express the NR-specific transporter, PnuC . We hypothesized that dietary NR supplementation would modify across intestinal sections. determined effects 12 weeks on composition segments high-fat diet-fed (HFD) rats. also explored in humans and mice....
Exercise/exercise training can enhance insulin sensitivity through adaptations in skeletal muscle, the primary site of insulin-mediated glucose disposal; however, humans range improvement vary substantially. The purpose this study was to determine if obesity influences magnitude exercise response relation improving human muscle. Electrical pulse stimulation (EPS; 24 h) muscle myotubes improved action tissue from both lean and severely obese individuals, but responses EPS were blunted with...
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...
Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in interorgan cross talk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin β4 (TMSB4X) as most upregulated secreted protein media of contracting C2C12 myotubes. TMSB4X was also acutely increased plasma exercising humans irrespective insulin resistance condition or exercise mode. Treatment mice with did not ameliorate metabolic...
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...
Increased lipolysis and free fatty acid (FFA) levels contribute significantly to the pathogenesis of chronic acute insulin resistance in type 2 diabetes, but underlying mechanisms are uncertain.Our objective was test whether increased FFA induced by withdrawal accompanied adipose tissue (AT) contents triglyceride lipase (ATGL) and/or altered intracellular ATGL regulation.Nine patients with diabetes were examined twice a randomized crossover design after 16 h 1) hyperglycemia/insulin 2)...
BackgroundThe obesogenic potential of high-fat diets (HFD) in rodents is attenuated when the protein:carbohydrate ratio increased. However, it not known if intake an HFD irrespective and absence weight gain, affects glucose homeostasis gut microbiota.MethodsWe fed C57BL6/J mice 3 different HFDs with decreasing ratios for 8 weeks compared results to a LFD reference group. We analyzed microbiota composition by 16S rDNA amplicon sequencing intestinal gene expression real-time PCR. Whole body...
In clinical trials, oral supplementation with nicotinamide riboside (NR) fails to increase muscle mitochondrial respiratory capacity and insulin sensitivity but also does not NAD+ levels. This study tests the feasibility of chronically elevating skeletal in mice investigates putative effects on capacity, sensitivity, gene expression. Accordingly, improve bioavailability muscle, we developed an experimental model for administering NR repeatedly through a jugular vein catheter. Mice Western...