A5084927745- Fibroblast Growth Factor Research
- Kruppel-like factors research
- Epigenetics and DNA Methylation
- Adipose Tissue and Metabolism
- Liver Disease Diagnosis and Treatment
- Diet, Metabolism, and Disease
- Pancreatic function and diabetes
- Sirtuins and Resveratrol in Medicine
- Diet and metabolism studies
- Pancreatitis Pathology and Treatment
- Fatty Acid Research and Health
- Regulation of Appetite and Obesity
- Diabetes Treatment and Management
- Alcohol Consumption and Health Effects
- Bariatric Surgery and Outcomes
- Genetic Syndromes and Imprinting
- Curcumin's Biomedical Applications
- Digestive system and related health
- Adipokines, Inflammation, and Metabolic Diseases
- Cannabis and Cannabinoid Research
- Phagocytosis and Immune Regulation
- Autophagy in Disease and Therapy
- Lipid metabolism and biosynthesis
- Aldose Reductase and Taurine
- Cardiovascular Disease and Adiposity
Novo Nordisk (Denmark)
2023-2025
Novo Nordisk Foundation
2015-2024
University of Copenhagen
2015-2024
Novo Nordisk (Germany)
2024
Novo Nordisk Foundation Center for Basic Metabolic Research
2022
Foundation Center
2022
Gentofte Hospital
2018-2019
University of Iowa
2011-2015
Howard Hughes Medical Institute
2008-2012
Yale University
2006-2011
OBJECTIVE Macrophage recruitment to adipose tissue is a reproducible feature of obesity. However, the events that result in chemokine production and macrophage during states energetic excess are not clear. Sirtuin 1 (SirT1) an essential nutrient-sensing histone deacetylase, which increased by caloric restriction reduced overfeeding. We discovered SirT1 depletion causes anorexia stimulating inflammatory factors white thus posit decreases link overnutrition inflammation. RESEARCH DESIGN AND...
BackgroundAlcohol use disorder (AUD) is a chronic, relapsing brain that accounts for 5% of deaths annually, and there an urgent need to develop new targets therapeutic intervention. The glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduces alcohol consumption in rodents nonhuman primates, but its efficacy patients with AUD unknown.MethodsIn randomized, double-blinded, placebo-controlled clinical trial, treatment-seeking were assigned receive (2 mg subcutaneously) or placebo once...
Adiponectin has insulin-sensitizing, antiatherogenic, and anti-inflammatory properties, but little is known about factors that regulate its secretion. To examine the effect of fish oil on adiponectin secretion, mice were fed either a control diet or isocaloric diets containing 27% safflower 27, 13.5, 8% menhaden oil. Within 15 days, feeding raised plasma concentrations two- to threefold in dose-dependent manner, remained approximately twofold higher for 7 days when was replaced by diet. 24...
Hepatic gluconeogenesis is a major contributing factor to hyperglycemia in the fasting and postprandial states type 2 diabetes mellitus (T2DM). Because Sirtuin 1 (SirT1) induces hepatic during through induction of phosphoenolpyruvate carboxylase kinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), glucose-6-phosphatase (G6Pase) gene transcription, we hypothesized that reducing SirT1, by using an antisense oligonucleotide (ASO), would decrease rat model T2DM. SirT1 ASO lowered both glucose...
Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show synthesis mitochondrial phospholipid cardiolipin indispensable for stimulating and sustaining function. Cardiolipin biosynthesis robustly induced brown beige adipose upon cold exposure. Mimicking through overexpression synthase (Crls1) enhances consumption mouse human adipocytes. Crls1 deficiency...
To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis (NASH) obese mouse models biopsy-confirmed NASH.Male wild-type C57BL/6J mice (DIO-NASH) and Lep ob/ob (ob/ob-NASH) were fed a diet high trans-fat (40%), fructose (20%) cholesterol (2%) 30 21 wk, respectively. Prior to treatment, all underwent liver biopsy confirmation stratification steatosis fibrosis, using fatty disease activity score (NAS) fibrosis staging system. The kept on received...
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...
Exercise has profound pleiotropic health benefits, yet the underlying mechanisms remain incompletely understood. Endocrine FGF21, bile acids (BAs), and BA-induced FGF19 have emerged as metabolic signaling molecules. Here, we investigated if dissimilar modes of exercise, resistance exercise (RE) endurance (EE), regulate plasma BAs, FGF19, FGF21 in humans.Ten healthy, moderately trained males were enrolled a randomized crossover study 1 hour bicycling at 70% VO2peak (EE) high-volume RE....
Invariant natural killer T cells (iNKTs) are innate-like that highly concentrated in the liver and recognize lipids presented on MHC-like molecule CD1d. Although capable of a myriad responses, few essential functions have been described for iNKTs. Among many cell types immune system implicated metabolic control disease, iNKTs seem ideally poised such role, yet little has done to elucidate possible function. We hypothesized lipid presentation by CD1d could report status engage regulate...
The unfolded protein response (UPR), induced by endoplasmic reticulum (ER) stress, regulates the expression of factors that restore folding homeostasis. However, in liver and kidney, ER stress also leads to lipid accumulation, accompanied at least transcriptional suppression metabolic genes. mechanisms this including which pathways contribute phenotype each organ, are unclear. We combined gene profiling, biochemical assays, untargeted lipidomics understand basis stress-dependent taking...
By 2030, nearly half of Americans will have nonalcoholic fatty liver disease. In part, this epidemic is fueled by the increasing consumption caloric sweeteners coupled with an innate capacity to convert sugar into fat via hepatic de novo lipogenesis. addition serving as substrates, monosaccharides also increase expression key enzymes involved in lipogenesis carbohydrate response element-binding protein (ChREBP). To determine whether ChREBP a potential therapeutic target, we decreased...
Excessive alcohol consumption is a leading cause of global morbidity and mortality. However, knowledge the biological factors that influence ad libitum intake may be incomplete. Two large studies recently linked variants in KLB locus with levels humans. encodes β-klotho, co-receptor for liver-derived hormone fibroblast growth factor 21 (FGF21). In mice, FGF21 reduces intake, human Fgf21 are enriched among heavy drinkers. Thus, liver limit by secreting FGF21. whether full-length, active...
Augmenting nicotinamide adenine dinucleotide (NAD+) metabolism through dietary provision of NAD+ precursor vitamins translates to improved glucose handling in rodent models obesity and diabetes. Preclinical evidence suggests that the NAD+/SIRT1 axis may be implicated modulating important gut-related aspects regulation. We sought test whether supplementation with riboside (NR) affects β-cell function, α-cell incretin hormone secretion as well circulating bile acid levels humans.A 12-week...
Caspase-1 is a cysteine protease that can be activated by both endogenous and exogenous inflammatory stimuli has been shown to have important functions in processes as diverse proteolytic activation of cytokines, cell death, membrane repair. Caspase-1-dependent production the cytokines IL-1 IL-18 also implicated regulation appetite, body weight, glucose homeostasis, lipid metabolism. Consistent with emerging views caspase-1 metabolic regulation, we find caspase-1-deficient mice dramatically...
Defective melanocortin signaling causes hyperphagic obesity in humans and the melanocortin-4 receptor knockout mouse (MC4R−/−). The human disease most commonly presents, however, as haploinsufficiency of MC4R. This study validates MC4R+/− a model that, like MC4R−/−, also exhibits sustained response to dietary fat. Furthermore, both saturated monounsaturated fats elicit this response. N-acylphosphatidylethanolamine (NAPE) is lipid induced after several hours high-fat feeding, if dysregulated,...
A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 PYY release, since BAs spill over from ileum we decided investigate ability stimulate colonic secretion. Using isolated perfused rat/mouse colon as well stimulation rat vivo, demonstrate that significantly enhance secretion with average increases 3.5- 2.9-fold,...
Idiopathic intracranial hypertension (IIH) is a neurometabolic disease with an increasing incidence. The pathophysiology unknown, but improvement of diagnosis and management requires discovery novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, secondarily, test for associations between identified metabolites severity.
Inflammation accompanies obesity and its comorbidities-type 2 diabetes, non-alcoholic fatty liver disease atherosclerosis, among others-and may contribute to their pathogenesis. Yet the cellular machinery that links nutrient sensing inflammation remains incompletely characterized. The protein deacetylase sirtuin-1 (SirT1) is activated by energy depletion plays a critical role in mammalian response fasting. More recently it has been implicated repression of inflammation. SirT1 mRNA expression...