A5055031885- Diabetes Treatment and Management
- Regulation of Appetite and Obesity
- Pancreatic function and diabetes
- Neuropeptides and Animal Physiology
- Diet and metabolism studies
- Bariatric Surgery and Outcomes
- Pharmacology and Obesity Treatment
- Metabolism, Diabetes, and Cancer
- Biochemical Analysis and Sensing Techniques
- Autophagy in Disease and Therapy
- Diet, Metabolism, and Disease
- interferon and immune responses
- Cannabis and Cannabinoid Research
- Chemical Synthesis and Analysis
- Hormonal Regulation and Hypertension
- Adipokines, Inflammation, and Metabolic Diseases
- Immune cells in cancer
- NF-κB Signaling Pathways
- Cancer, Hypoxia, and Metabolism
- Retinal Development and Disorders
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
- Hemodynamic Monitoring and Therapy
- Adenosine and Purinergic Signaling
- Nitric Oxide and Endothelin Effects
Novo Nordisk Foundation
2024-2025
University of Copenhagen
2024-2025
Imperial College London
2014-2023
Inserm
2021-2022
Université Paris Cité
2022
Institut Necker Enfants Malades
2022
Centre National de la Recherche Scientifique
2022
Sorbonne Université
2022
Centre de Recherche des Cordeliers
2022
American Society for Investigative Pathology
2020
Obesity is a growing epidemic, and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs that aim to cause effective weight loss with minimal side effects. Both glucagon GLP-1 reduce appetite loss. Additionally, increases energy expenditure. We hypothesized combination both peptides, administered at doses are individually subanorectic, would appetite, while protect against hyperglycemic effect glucagon. In this...
OBJECTIVE Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and YY (PYY). Subcutaneous infusion these hormones (“GOP”), mimicking levels, reduces energy intake. Our objective was to study the effects GOP on glycemia body weight when given for 4 weeks patients with diabetes obesity. RESEARCH DESIGN AND METHODS In this single-blinded mechanistic study, obese prediabetes/diabetes were randomized (n = 15) or saline 11) weeks....
Mitophagy degrades damaged mitochondria, but we show here that it can also target functional mitochondria. This latter scenario occurs during programmed mitophagy and involves the receptors NIX BNIP3. Although AMP-activated protein kinase (AMPK), energy-sensing kinase, influence damaged-induced mitophagy, its role in is unclear. We found AMPK directly inhibits NIX-dependent by triggering 14-3-3-mediated sequestration of ULK1, via ULK1 phosphorylation at two sites: Ser556 an additional...
Nutrient deprivation is a major trigger of autophagy, conserved quality control and recycling process essential for cellular tissue homeostasis. In high-content image-based screen the human ubiquitome, we here identify E3 ligase Pellino 3 (PELI3) as crucial regulator starvation-induced autophagy. Mechanistically, PELI3 localizes to autophagic membranes, where it interacts with ATG8 proteins through an LC3-interacting region (LIR). This facilitates PELI3-mediated ubiquitination ULK1, driving...
Inhibition of AMP-activated protein kinase (AMPK) is under increasing investigation for its therapeutic potential in many diseases, including certain cancers. However, existing AMPK-inhibitors available as tool compounds are largely limited to compound C/dorsomorphin and SBI-0206965, both which suffer from poor selectivity off-target effects. Here we describe the structure-based molecular insights cellular actions a recently identified potent AMPK inhibitor, BAY-3827. Kinase profiling...
Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous antagonist and inverse agonist of the ghrelin receptor, countering ghrelin's effects on cell signaling feeding. However, despite emerging interest in LEAP2's physiology pharmacology, its endocrine regulation remains unclear. Here, we report that plasma LEAP2 levels decrease significantly upon glucagon infusions during somatostatin clamps humans. This effect preserved patients with obesity type diabetes while diminished...
Abstract The purpose of this study was to determine whether an age‐related increase in photoreactivity human retinal melanosomes (MS) can cause phototoxicity pigment epithelium (RPE) cells. MS were isolated post mortem from young (20–30 years, [YHMs]) and old (60–90 [OHMs]) eyes bovine (bovine [BMs]). Confluent cultured ARPE‐19 cells fed equivalent numbers OHMs or BMs accumulated similar amounts melanin as determined by electron paramagnetic resonance assay. Cells with without either...
Hyperglucagonemia is a key pathophysiological driver of type 2 diabetes. Although Roux-en-Y gastric bypass (RYGB) highly effective treatment for diabetes, it presently unclear how surgery alters glucagon physiology. The aim this study was to characterize the behavior proglucagon-derived peptide (glucagon, glucagon-like peptide-1 (GLP-1), oxyntomodulin, glicentin) secretion after RYGB surgery.Prospective 19 patients with obesity and pre-diabetes/diabetes undergoing RYGB. We assessed glucose,...
Adipose tissue macrophages (ATM) adapt to changes in their energetic microenvironment. Caloric excess, a range from transient diet-induced obesity, could result the transition of ATMs highly oxidative and protective inflammatory metabolically deleterious. Here, we demonstrate that Interferon Regulatory Factor 5 (IRF5) is key regulator macrophage capacity response caloric excess. mice with genetic-deficiency Irf5 are characterised by increased respiration mitochondrial membrane potential....
Pancreatic polypeptide (PP) is a gut hormone that acts on Y4 receptors to reduce appetite. Obese humans display reduced postprandial increase in PP and remain fully sensitive the anorectic effects of exogenous PP. The utility as an anti-obesity treatment limited by its short circulating half-life. Insight into mechanisms which degraded could aid design long-acting analogs. We investigated role peptidases degradation determine whether inhibition these enzymes enhanced plasma levels...
Abstract Background Constitutional thinness (CT), a non‐malnourished underweight state with no eating disorders, is characterized by weight gain resistance to high fat diet. Data issued from muscle biopsies suggested blunted anabolic mechanisms in free‐living state. Weight and metabolic responses protein caloric supplementation has not been yet explored CT. Methods A 2 week overfeeding (additional 600 kcal, 30 g protein, 72 carbohydrate, 21 fat) was performed compare two groups of CTs (12...
Summary Methionine-1 (M1)-linked ubiquitin chains, assembled by the ligase LUBAC and cleaved deubiquitinase OTULIN, are critical regulators of inflammation immune homeostasis. Genetic loss either or OTULIN causes autoinflammatory syndromes, which associated with defects in glycogen lipid metabolism. However, how regulate metabolic signalling remains unknown. Here, we demonstrate that promotes, while restricts, activation key regulator AMP-activated protein kinase (AMPK) cells, mice, human...
Oral CDCA and UDCA have different effects on gut pancreatic hormone secretion. A single dose of increased fasting secretion the hormones GLP-1 OXM with an accompanying increase in insulin also reduced postprandial GIP secretion, which was associated insulin. In contrast, did not change or postprandially. could be beneficial to patients obesity diabetes.
Abstract Objectives Peptide tyrosine (PYY) exists as two species, PYY 1‐36 and 3‐36 , with distinct effects on insulin secretion appetite regulation. The detailed of bariatric surgery are not known previous studies have used nonspecific immunoassays to measure total PYY. Our objective was characterize the effect sleeve gastrectomy (SG) Roux‐en‐Y gastric bypass (RYGB) fasting postprandial using a newly developed liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) assay. Design Subjects...
Glucokinase (GK) is highly expressed in the hypothalamic paraventricular nucleus (PVN); however, its role currently unknown. We found that GK PVN acts as part of a glucose-sensing mechanism within regulates glucose homeostasis by controlling glucagon-like peptide 1 (GLP-1) release. GLP-1 released from enteroendocrine L cells response to oral glucose. Here we identify brain critical release show increasing expression or injection into increases On contrary, decreasing nonmetabolizable...
Activation of ghrelin is controlled by the enzyme ghrelin- O-acyl transferase (GOAT). In humans, localization this acylation poorly understood. The aim study to explore GOAT and activation in human liver evaluating both bioactive non-bioactive bloodstream entering leaving simultaneously evaluate mRNA expression liver. A healthy part oncologic hepatic tissue collected from nine patients undergoing hepatectomy was used quantitative real-time polymerase chain reaction (RT-qPCR). Simultaneously,...
Abstract Transcription Factor EB (TFEB) is a critical regulator of lysosomal biogenesis, autophagy and energy homeostasis through controlling expression genes belonging to the coordinated regulation network. AMP-activated protein kinase (AMPK) has been reported phosphorylate TFEB at three conserved C-terminal serine residues (S466, S467, S469) these phosphorylation events were essential for transcriptional activation TFEB. In sharp contrast this proposition, here we demonstrate that AMPK...
Purpose/aim of the study: The pharmacokinetic (PK) parameters in animal models can help optimize novel candidate drugs prior to human trials. However, due complexity experiments, their use is limited academia. We present a surgical rat model for investigation and its an anti-obesity drug development program. Materials methods: uses anesthetized male Wistar rats, jugular, femoral catheter, insulin pump peptide infusion. following were measured: metabolic clearance rate (MCR), half-life,...
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)
We note that Maurer et al., in their correspondence,1 have raised some concerns about the preanalytical and analytical validation of peptide YY (PYY) assay described our paper ‘The postprandial secretion YY1–36 3–36 obesity is differentially increased after gastric bypass versus sleeve gastrectomy’.2 The characteristics were not primary objectives paper. focussed on physiology PYY healthy volunteers patients pre- post-gastric gastrectomy. Therefore, we did include a full description details...