Niklas Mejhert
A5061540235- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Lipid metabolism and biosynthesis
- RNA Research and Splicing
- MicroRNA in disease regulation
- Cardiovascular Disease and Adiposity
- Endoplasmic Reticulum Stress and Disease
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Peroxisome Proliferator-Activated Receptors
- Microbial Metabolic Engineering and Bioproduction
- Metabolism, Diabetes, and Cancer
- Fibroblast Growth Factor Research
- Medical and Biological Sciences
- Cancer-related molecular mechanisms research
- Regulation of Appetite and Obesity
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Circadian rhythm and melatonin
- Muscle Physiology and Disorders
- Single-cell and spatial transcriptomics
- Metabolomics and Mass Spectrometry Studies
- Cell Image Analysis Techniques
- Genomics and Chromatin Dynamics
Karolinska University Hospital
2010-2024
Karolinska Institutet
2014-2024
Steno Diabetes Centers
2024
Harvard University
2017-2022
Broad Institute
2020
Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets genes has not been previously studied en masse. Exploiting the fact active are transcribed, we simultaneously measured their activity in 19 human 14 mouse time courses covering a wide range cell types biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated earliest responses....
In obesity, white adipose tissue (WAT) inflammation is linked to insulin resistance. Increased adipocyte chemokine (C-C motif) ligand 2 (CCL2) secretion may initiate by attracting the migration of inflammatory cells into tissue. Using an unbiased approach, we identified microRNAs (miRNAs) that are dysregulated in human obesity and assessed their possible role controlling CCL2 production. subcutaneous WAT obtained from 56 subjects, 11 miRNAs were present all subjects downregulated obesity. Of...
Abstract In the FANTOM5 project, transcription initiation events across human and mouse genomes were mapped at a single base-pair resolution their frequencies monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands samples, consisting variety primary cells, tissues, cell lines, time series samples during activation development, subjected to uniform pipeline data production. The analysis started measuring RNA extracts assess...
The contribution of cellular heterogeneity and architecture to white adipose tissue (WAT) function is poorly understood. Herein, we combined spatially resolved transcriptional profiling with single-cell RNA sequencing image analyses map human WAT composition structure. This identified 18 cell classes unique propensities form organized homo- heterotypic clusters. Of these, three constituted mature adipocytes that were similar in size, but distinct their spatial arrangements profiles. Based on...
Abstract Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity 1,2 . However, maintaining loss considerable challenge, especially as the seems retain an obesogenic memory that defends against changes 3,4 Overcoming this barrier for long-term treatment success difficult because molecular mechanisms underpinning phenomenon remain largely unknown. Here, by using single-nucleus RNA sequencing, we show both human mouse adipose tissues...
Partial inhibition of adipose tissue lipolysis does not increase fat mass but improves glucose metabolism and insulin sensitivity through modulation fatty acid turnover induction cell de novo lipogenesis.
Wnt signaling regulates adipogenesis and adipocyte function. Secreted frizzled-related proteins (SFRPs) are a family of secreted (SFRP1-5) that bind inhibit Wnts. Several members, including SFRP5, have recently been implicated in dysfunction obesity.Our objective was to characterize the expression, secretion, function SFRP human white adipose tissue (WAT) fat cells.SFRP1-5 mRNA expression measured sc visceral WAT from lean obese individuals correlated insulin sensitivity. secretion explants...
The regulatory gene pathways that accompany loss of adipose tissue in cancer cachexia are unknown and were explored using pangenomic transcriptome profiling. Global expression profiles abdominal subcutaneous studied gastrointestinal patients with (n=13) or without (n=14) cachexia. Cachexia was accompanied by preferential decreased fat cell volume, but not number. Adipose regulating energy turnover upregulated, whereas genes related to structure (cellular adhesion, extracellular matrix actin...
OBJECTIVE Large subcutaneous fat cells associate with insulin resistance and high risk of developing type 2 diabetes. We investigated if changes in cell volume mass correlate improvements the metabolic profile after bariatric surgery obese patients. RESEARCH DESIGN AND METHODS Fat number were measured abdominal adipose tissue 62 women before years Roux-en-Y gastric bypass (RYGB). Regional body by dual-energy X-ray absorptiometry; sensitivity hyperinsulinemic-euglycemic clamp; plasma glucose,...
Nonalcoholic fatty liver disease (NAFLD) is characterized by excess lipid accumulation in hepatocytes and represents a huge public health problem owing to its propensity progress nonalcoholic steatohepatitis, fibrosis, failure. The lipids stored hepatic steatosis (HS) are primarily triglycerides (TGs) synthesized two acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. Either DGAT1 or DGAT2 catalyzes this reaction, these enzymes have been suggested differentially utilize exogenous...
Obesity and type 2 diabetes are strongly associated with adipose tissue dysfunction impaired adipogenesis. Understanding the molecular underpinnings that control adipogenesis is thus of fundamental importance for development novel therapeutics against metabolic disorders. However, translational approaches hampered as current models do not accurately recapitulate Here, a scaffold-free versatile 3D adipocyte culture platform chemically defined conditions presented in which primary human...
Lipid droplets (LDs) are organelles of cellular lipid storage with fundamental roles in energy metabolism and cell membrane homeostasis. There has been an explosion research into the biology LDs, part due to their relevance diseases storage, such as atherosclerosis, obesity, type 2 diabetes, hepatic steatosis. Consequently, there is increasing need for a resource that combines datasets from systematic analyses LD biology. Here, we integrate high-confidence, systematically generated human,...
Abstract The mechanisms promoting disturbed white adipocyte function in obesity remain largely unclear. Herein, we integrate adipose tissue (WAT) metabolomic and transcriptomic data from clinical cohorts find that the WAT phosphocreatine/creatine ratio is increased creatine kinase-B expression activity decreased obese state. In human vitro murine vivo models, demonstrate phosphocreatine metabolism adipocytes alters adenosine monophosphate-activated protein kinase via effects on...
White adipocytes function as major energy reservoirs in humans by storing substantial amounts of triglycerides, and their dysfunction is associated with metabolic disorders; however, the mechanisms underlying cellular specialization during adipogenesis remain unknown. Here, we generate a spatiotemporal proteomic atlas human adipogenesis, which elucidates remodelling well spatial reorganization pathways to optimize cells for lipid accumulation highlights coordinated regulation protein...
Glutamine and glutamate are interconverted by several enzymes alterations in this metabolic cycle linked to cardiometabolic traits. Herein, we show that obesity-associated insulin resistance is characterized decreased plasma white adipose tissue glutamine-to-glutamate ratios. We couple these stoichiometric changes perturbed fat cell glutaminase glutamine synthase messenger RNA protein abundance, which together promote glutaminolysis. In human adipocytes, reductions activity aerobic...
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have multiple effects in various tissues including adipose inflammation, a condition characterized by increased local release of the pro-lipolytic cytokine tumor necrosis factor-alpha (TNF-α). Whether miRNAs adipocyte lipolysis is unknown. We set out to determine whether affect human fat cells. To this end, eleven known be present tissue were over-expressed vitro differentiated adipocytes followed assessments...
White adipose tissue (WAT) expands in part through adipogenesis, a process involving fat cell generation and fatty acid (FA) storage into triglycerides (TGs). Several findings suggest that inter-individual regional variations adipogenesis are linked to metabolic complications. We aimed identify cellular markers define human adipocyte progenitors (APs) with pronounced adipogenic/TG ability. Using an unbiased single screen of passaged adipose-derived stromal cells (hADSCs), we identified...