A5011043460- Liver Disease Diagnosis and Treatment
- Adipose Tissue and Metabolism
- Gut microbiota and health
- Diet and metabolism studies
- Drug Transport and Resistance Mechanisms
- Lipid metabolism and biosynthesis
- Adipokines, Inflammation, and Metabolic Diseases
- Genetics, Aging, and Longevity in Model Organisms
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- Lipid metabolism and disorders
- Regulation of Appetite and Obesity
- Birth, Development, and Health
- Clostridium difficile and Clostridium perfringens research
- Sphingolipid Metabolism and Signaling
- Phagocytosis and Immune Regulation
- Immune Response and Inflammation
- Botanical Research and Chemistry
- Lipoproteins and Cardiovascular Health
- interferon and immune responses
- Drug-Induced Hepatotoxicity and Protection
- Alzheimer's disease research and treatments
- Pancreatitis Pathology and Treatment
- Plant Toxicity and Pharmacological Properties
- Ion Transport and Channel Regulation
University of Gothenburg
2020-2025
Sahlgrenska University Hospital
2021-2025
AstraZeneca (Sweden)
2021-2024
AstraZeneca (Brazil)
2023
Wallenberg Wood Science Center
2020-2021
Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in MetaCardis cohort three European countries have elevated serum imidazole levels. Furthermore, levels were increased low bacterial gene richness Bacteroides 2 enterotype, previously been associated obesity. The enterotype was also...
Objective Dietary fibres are essential for maintaining microbial diversity and the gut microbiota can modulate host physiology by metabolising fibres. Here, we investigated whether soluble dietary fibre oligofructose improves metabolism modulating bacterial transformation of secondary bile acids in mice fed western-style diet. Design To assess impact supplementation on acid bacteria, conventional wild-type TGR5 knockout diet enriched or not with cellulose oligofructose. In addition, used...
Over the past years, it has become clear that microbial ecosystem in gut a profound capacity to interact with host through production of wide range bioactive metabolites. The microbially produced metabolite imidazole propionate (ImP) is clinically and mechanistically linked insulin resistance type 2 diabetes, but unclear how ImP associated heart failure. authors aimed explore whether failure mortality. serum measurements large independent clinical cohorts patients (European [n = 1,985] North...
Abstract Alterations in gut microbiota composition are suggested to contribute cardiometabolic diseases, part by producing bioactive molecules. Some of the metabolites produced very low abundant bacterial taxa, which largely have been neglected due limits detection. However, concentration microbially from these taxa can still reach high levels and substantial impact on host physiology. To explore this concept, we focused generation secondary bile acids 7α-dehydroxylating bacteria...
Immunological control of viral infections in the brain exerts immediate protection and also long-term maintenance integrity. Microglia are important for antiviral defense brain. Here, we report that herpes simplex virus type 1 (HSV1) infection human induced pluripotent stem cell (hiPSC)–derived microglia down-regulates expression genes TREM2 pathway. was found to be virus-induced IFNB induction through DNA-sensing cGAS-STING pathway phagocytosis HSV1-infected neurons. Consequently, depletion...
Insulin-PI3K signaling controls insulin secretion. Understanding this feedback mechanism is crucial for comprehending how functions. However, the role of adipocyte insulin-PI3K in controlling secretion vivo remains unclear. Using adipocyte-specific PI3Kα knockout mice (PI3Kα
The intestinal mucus layer is a physical barrier separating the tremendous number of gut bacteria from host epithelium. Defects in have been linked to metabolic diseases, but previous studies predominantly investigated function during high-caloric/low-fiber dietary interventions, thus making it difficult separate effects mediated directly through diet quality potential obesity-dependent effects. As such, we decided examine mouse models with disease distinguish these factors. Here show that,...
Objective Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode action specific microbes in health remain elusive. Previously, we identified commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity subjects MetS. In this proof-of-concept study, investigated potential therapeutic effects A. L2-7 on systemic responses duodenal transcriptome profiles individuals Design...
Abstract The cellular membrane in male meiotic germ cells contains a unique class of phospholipids and sphingolipids that is required for reproduction. Here, we show conserved fluidity sensor, AdipoR2, regulates the meiosis-specific lipidome mouse testes by promoting synthesis containing very-long-chain polyunsaturated fatty acids (VLC-PUFAs). AdipoR2 upregulates expression acid elongase, ELOVL2, both transcriptionally post-transcriptionally, to synthesize VLC-PUFA. depletion VLC-PUFAs...
Abstract Cells and organisms require proper membrane composition to function develop. Phospholipids are the major component of membranes primarily acquired through diet. Given great variability in diet composition, cells must be able deploy mechanisms that correct deviations from optimal properties. Here, using lipidomics unbiased proteomics, we found embryonic lethality mice lacking fluidity regulators Adiponectin Receptors 1 2 (AdipoR1/2) is associated with aberrant high saturation...
The human AdipoR2 and its Caenorhabditis elegans homolog PAQR-2 are multipass plasma membrane proteins that protect cells against rigidification. However, how promotes fluidity mechanistically is not clear. Using 13C-labeled fatty acids, we show can promote the elongation incorporation of membrane-fluidizing polyunsaturated acids into phospholipids. To elucidate molecular basis these activities, performed immunoprecipitations tagged expressed in HEK293 or whole C. elegans, respectively,...
Bariatric surgery is an effective treatment option for obesity and provides long-term weight loss positive effects on metabolism, but the underlying mechanisms are poorly understood. Alterations in bile acid metabolism have been suggested as a potential contributing factor, comprehensive studies humans lacking.
Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids membrane lipids that important for cellular structure function, dysfunction is a characteristic rare monogenic diseases defects in glycosphingolipid synthesis turnover. However, it not known how glycosphingolipids regulate processes heart. The aim this study to determine role heart function.
BackgroundApolipoprotein C-III (apoC-III) is a regulator of triglyceride (TG) metabolism, and due to its association with risk cardiovascular disease, an emergent target for pharmacological intervention. The impact substantially lowering apoC-III on lipoprotein metabolism not clear.MethodsWe investigated the kinetics apolipoproteins B48 B100 (apoB48 apoB100) in chylomicrons, VLDL1, VLDL2, IDL, LDL patients heterozygous loss-of-function (LOF) mutation APOC3 gene. Studies were conducted...
Dietary antioxidants and supplements are widely used to protect against cancer, even though it is now clear that can promote tumor progression by helping cancer cells overcome barriers of oxidative stress. Although recent studies have, in great detail, explored the role lung skin tumors driven RAS RAF mutations, little known about impact antioxidant supplementation on other cancers, including Wnt-driven originating from gut. Here, we show with N-acetylcysteine (NAC) vitamin E promotes...
Abstract Communicating editor: B. Grant The composition and biophysical properties of cellular membranes must be tightly regulated to maintain the proper functions myriad processes within cells. To better understand importance membrane homeostasis, we assembled a panel five Caenorhabditis elegans strains that show wide span properties, ranging from excessively rich in saturated fatty acids (SFAs) rigid polyunsaturated (PUFAs) fluid. genotypes strain are, most fluid: paqr-1(tm3262);...
BACKGROUND: The microbially produced amino acid–derived metabolite imidazole propionate (ImP) contributes to the pathogenesis of type 2 diabetes. However, effects ImP on endothelial cell (EC) physiology and its role in atherosclerotic coronary artery disease are unknown. Using both human animal model studies, we investigated potential contributory development atherosclerosis. METHODS: Plasma levels were measured patients undergoing elective cardiac angiography (n=831) by ultra-high...
Sucrose-rich diets promote hepatic de novo lipogenesis (DNL) and steatosis through interactions with the gut microbiota. However, role of sugar-microbiota dynamics in absence dietary fat remains unclear. This study aimed to investigate effects a high-sucrose, zero-fat diet (ZFD) on host metabolism conventionally raised (CONVR) germ-free (GF) mice. CONVR GF mice were fed ZFD, lipid accumulation, gene expression, metabolite levels analyzed. DNL activity was assessed by measuring malonyl-CoA...
How cells maintain vital membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remains largely unknown. Here, we report the first whole-organism (Caenorhabditis elegans) forward genetic screen to identify genes essential for tolerance dietary saturated (SFAs). We found that only PAQR-2/IGLR-2 pathway, homologous human adiponectin receptor 2 (AdipoR2) is uniquely prevent SFA-mediated toxicity. When provided SFA-rich diet, worms lacking either...
How cells maintain vital membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remains largely unknown. Here, we used transcriptomics, lipidomics, growth and respiration assays, property analyses in human HEK293 or umbilical vein endothelial (HUVEC) to show that the function AdipoR2 is respond rigidification by regulating many metabolism genes. We also AdipoR2-dependent critical for challenged with saturated acids. Additionally, found deficiency...
Cancer cells produce high levels of mitochondria-associated reactive oxygen species (ROS) that can damage macromolecules, but also promote cell signaling and proliferation. Therefore, mitochondria-targeted antioxidants have been suggested to be useful in anti-cancer therapy, no studies convincingly addressed this question. Here, we administered the MitoQ MitoTEMPO mice with BRAF-induced malignant melanoma KRAS-induced lung cancer, found these compounds had impact on number primary tumors...
Abstract Background Patients with familial hypercholesterolemia (FH) display high levels of low‐density lipoprotein cholesterol (LDL‐c), endothelial dysfunction, and increased risk premature atherosclerosis. We have previously shown that red blood cells (RBCs) from patients type 2 diabetes induce dysfunction through arginase 1 reactive oxygen species (ROS). Objective To test the hypothesis RBCs FH (FH‐RBCs) elevated LDL‐c dysfunction. Methods results FH‐RBCs >5.0 mM induced following 18‐h...