Biology subjects

Nielsen, J.

Publications and source records attributed to Nielsen, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Gene model for the ortholog of raptor in Drosophila eugracilis

Gene model for the ortholog of raptor in the D. eugracilis Apr. 2013 (BCM-HGSC/Deug_2.0) (DeugGB2) Genome Assembly (GenBank Accession: GCA_000236325.2) of Drosophila eugracilis. This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.

genomics↗

bioRxiv2026

Gene model for the ortholog of raptor in Drosophila erecta

Gene model for the ortholog of raptor in the May 2011 (Agencourt Dere_CAF1/DereCAF1) Genome Assembly (GenBank Accession: GCA_000005135.1) of Drosophila erecta. This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.

genomics↗

bioRxiv2026

Gene model for the ortholog of raptor in Drosophila grimshawi

Gene model for the ortholog of raptor in the D. grimshawi May 2011 (Agencourt dgri_caf1/DgriCAF1) Genome Assembly (GenBank Accession: GCA_000005155.1) of Drosophila grimshawi. This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.

genomics↗

bioRxiv2026

Rac1 deficiency reduces mitochondrial respiratory capacity, impairs fatty acid metabolism and causes muscle wasting

BackgroundThe age-related progressive decline in skeletal muscle function is characterised by declining mitochondrial quality control and perturbed fatty acid metabolism, contributing to frailty and increased mortality. The actin cytoskeleton, a key structural component of skeletal muscle, has recently been implicated in mitochondrial anchoring and dynamics. However, the role of actin-regulating proteins, including the Rho GTPase Rac1, in mitochondrial function and age-associated metabolic and functional muscle deterioration remains undefined. MethodsSkeletal muscle from mice with inducible muscle-specific deletion of Rac1 (Rac1 imKO) underwent unbiased mass spectrometry-based proteomic profiling. Mitochondrial morphology was assessed by transmission electron microscopy, and physiological parameters, including muscle mass and contraction-stimulated palmitate oxidation in isolated soleus muscle, were evaluated. Mitochondrial respiratory function was determined by high-resolution respirometry in permeabilised gastrocnemius skeletal muscle fibre bundles. Biochemically, muscular triacylglycerol (TG) content, mRNA (qPCR) and protein (immunoblotting) content were determined. In vastus lateralis muscle biopsies from healthy, untrained young (20-30 years) and old, sarcopenic (83-94 years) men, Rac1 and mitochondrial respiratory protein abundances were measured. A complementary human genetic association analysis was performed using the FinnGen dataset. ResultsRac1 deficiency triggered muscle wasting in middle-aged mice (Gastrocnemius: -10%; Quadriceps: -7%). Preceding muscle wasting, gene set enrichment analysis identified enrichment in fatty acid metabolism and oxidative phosphorylation pathways, consistent with increased mitochondrial volume density in Rac1 imKO muscle (subsarcolemmal: +467%; intermyofibrillar: +166%). Despite mitochondrial expansion at this stage, Rac1 deficiency attenuated the increase in palmitate oxidation in response to muscle contraction (-62%). At the muscle-wasting stage, Rac1 imKO muscle exhibited reduced mitochondrial respiratory capacity (-25-32%). Additionally, the mitochondrial dysfunction was associated with an accumulation of muscle TG (+78%, p = 0.096) and upregulation of fatty acid transporter, CD36 protein content (+25%), indicative of altered fatty acid handling. In humans, Rac1 muscle protein content was increased in old, sarcopenic subjects compared to young (+41%), and negatively correlated with quadriceps cross-sectional area (CSA) (r = -0.475) and type II fibre CSA (r = -0.466). In old, sarcopenic muscle, Rac1 protein content correlated negatively with protein content of multiple mitochondrial respiratory complexes (CI: r = -0.690, CIV: r = -0.938, CV: r = -0.704). GWAS further identified associations between Rac1 SNP variants and lipid metabolic and muscle-wasting diseases. ConclusionsMuscle Rac1 deficiency reduces mitochondrial respiratory capacity and metabolic flexibility through impaired fatty acid metabolism, leading to muscle wasting and highlighting a potential therapeutic target in age-related functional decline.

Molecular Biology↗

bioRxiv2026

Biosynthesis of bisbenzylisoquinoline alkaloids

Bisbenzylisoquinoline alkaloids (bisBIAs) are pharmacologically valuable plant metabolites with complex stereochemical architectures, yet the catalytic principles governing their assembly have remained largely unclear. Here, we elucidate the enzymatic pathway to cyclic bisBIAs and uncover a non-canonical redox-mediated mechanism for post-assembly stereochemical control. We identify cytochrome P450 enzymes that catalyze regioselective oxidative dimerization and macrocyclization of benzylisoquinoline monomers, establishing the macrocyclic scaffold. Subsequent stereochemical specification is achieved by a paired oxidase-reductase module that selectively epimerizes a single stereocenter through a transient imine formation, converting (R,S)-configured intermediates to (S,S)-products. Reconstitution of the pathway in yeast enabled production of both native bisBIAs and non-natural analogs, demonstrating pathway modularity and engineering potential. These results establish the biochemical principle underlying bisBIA biosynthesis and provide a framework for programmable biosynthesis of these complex natural products.

biochemistry↗

bioRxiv2026

Stable isotopes (δ13C, δ15N, δ34S) suggest eelgrass (Zostera sp.) foddering of Late Iron Age sheep (Ovis aries) in Denmark

Stable isotope analysis provides an important tool for reconstructing past livestock management practices and landscape use. However, isotopic data for sheep from Late Iron Age (AD 375/400-1050) Denmark remain limited. Here, we present bulk bone collagen {delta}{superscript 1}3C, {delta}{superscript 1}N, and {delta}3S isotope analyses of 27 sheep (Ovis aries) from six archaeological sites in Denmark, dated to the Germanic Iron Age (AD 375/400-750) and Viking Age (AD 750-1050). The analysed sheep exhibit a consistent pattern of enriched {delta}13C values relative to previously published isotopic datasets for Scandinavian livestock, while {delta}15N values display substantial inter-individual variability. Sulfur isotope values fall within moderate ranges consistent with mixed terrestrial and coastal environmental influences. The decoupling of {delta}13C enrichment from elevated {delta}15N values suggests that the observed carbon isotope signal does not reflect marine protein consumption but rather the incorporation of a 13C-enriched plant resource into sheep diets. We propose that eelgrass (Zostera sp.), either through direct grazing in coastal environments or supplementary foddering with harvested eelgrass, represents a plausible dietary source to explain this isotopic pattern. The results indicate that Late Iron Age sheep management strategies in Denmark incorporated coastal plant resources within flexible pastoral systems, potentially supporting intensified wool production associated with expanding textile economies. HighlightsO_LIStable isotope values of Late Iron Age sheep show some dietary marine input. C_LIO_LIEnriched {delta}13C values suggest eelgrass as supplementary fodder. C_LIO_LI{delta}34S values indicate adaptive grazing across coastal and inland landscapes. C_LI

zoology↗

bioRxiv2026

Investigation of Regulation and Binding Patterns of the Human Cathelicidin Peptide LL-37 in Complexation with Nucleic Acids, and its Impact on Neutrophil Extracellular Traps

The human cathelicidin host defense peptide LL-37 forms complexes with nucleic acids that can have either beneficial or detrimental health effects. We suggest that these differential impacts are directly connected to dsDNA binding by LL-37 and to complex formation between protomers. Here, we show using phage {lambda} DNA that LL-37 binds non-specifically to dsDNA, condensing it, followed by complex formation between LL-37 peptides. We find that complex formation is concentration-dependent, with low LL-37 amounts yielding loosely aggregated DNA structures, while higher LL-37 concentrations lead to well-defined, disc-like structures of about 150 nm in diameter. The condensation of the nucleic acids, which causes a loss of the characteristic B-DNA features, results from interactions of the phosphodiester backbone with protonated amino acid side chains of the peptide at physiological pH, predominantly in A-T rich sequences of the nucleic acid. However, in our studies, electrostatic interactions did not appear to be the driving force for complexation, but rather we found the -helical structure of the peptide with its amphipathic and hydrophobic surfaces to be essential. Further, we show that LL-37 also interacts with nucleic acids from neutrophil extracellular traps (NETs) in a concentration-dependent way, causing a reduction in NET aggregate area, which may offer new biophysical insights into diseases such as systemic lupus erythematosus (SLE), which involve slower-than-normal NET clearance. Our results indicate the key importance of LL-37 expression levels for regulation of the innate immune system for optimal human health, since the relative amounts of expressed LL-37 present to interact with extracellular DNA will determine the extent to which the DNA can be condensed, which in turn will affect the ability of the body to clear the NETs before they can cause inflammatory conditions.

biophysics↗

bioRxiv2026

A semantic segmentation model to predict subcellular glycogen localization using transmission electron microscopy images

Transmission electron microscopy (TEM) is the gold standard for assessing subcellular glycogen localization in skeletal muscle fibres, but conventional manual analysis is extremely time-consuming and limits large-scale studies. Here, we developed and validated a deep learning-based semantic segmentation approach to automate quantification of glycogen particles across defined subcellular compartments in human skeletal muscle. Skeletal muscle biopsies were obtained from seven healthy men under conditions of normal, depleted, and supercompensated glycogen content. TEM images were acquired from myofibrillar and subsarcolemmal regions and manually annotated to train two complementary attention U-Net models: a region model identifying subcellular structures (intermyofibrillar space, intramyofibrillar regions including A-band, I-band and Z-disc, and mitochondria) and a glycogen model detecting individual glycogen particles. Combining the two models enabled estimation of compartment-specific glycogen areal densities. Model performance was evaluated against manual point-counting. At the fibre level, estimates based on 10-12 images per region achieved biases below 15% and coefficient of variation below 26% for all compartments. Importantly, model-derived total glycogen volume density showed strong concordance with biochemically determined muscle glycogen content across biopsies. In conclusion, this validated semantic segmentation workflow provides a robust, objective, and highly time-efficient tool for quantifying subcellular glycogen distribution in skeletal muscle. The model substantially reduces analysis time and enables high-throughput investigations of compartmentalized glycogen metabolism, with model weights and code made openly available.

physiology↗

bioRxiv2025

Exercise training improves sarcopenic muscle function via restoration of mitochondrial quality control

Mitophagy is an essential component of the mitochondrial quality control program, maintaining mitochondrial homeostasis in metabolic tissues such as skeletal muscle. With age, it is thought that mitochondrial quality control becomes dysregulated, leading to the progression of age-associated diseases such as sarcopenia. Exercise is known to enhance skeletal muscle mitochondrial health and may be an effective intervention to prevent sarcopenia, however the role of mitophagy in this process is unknown. Utilising mitophagy reporter mice (mito-QC), we assessed adaptations in skeletal muscle mitophagy in response to increased age (3-26 months) and following an 8-week endurance exercise training period. Immunofluorescent imaging revealed that ageing led to an accumulation of mitolysosomes in sarcopenic old mice indicative of increased mitophagy, an adaptive response that was reversed by exercise training. In parallel to reducing age-associated mitophagy, exercise training increased mitochondrial respiratory capacity and improved muscle strength, suggesting that alterations in mitochondrial quality control led to improvements in skeletal muscle function. Exercise-mediated alterations in mitophagy were accompanied by increases in BNIP3, FUNDC1 and BCL2L13 protein content post training. Collectively our data suggests that sarcopenia leads to dysregulation of mitophagy in skeletal muscle. Restoring mitophagy balance with exercise training leads to improvements in mitochondrial respiration and skeletal muscle strength, identifying a novel cellular mechanism to explain the benefits of exercise training in old age.

cell biology↗

bioRxiv2025

Mitochondrial cristae density is increased following high-intensity interval training in patients with type 2 diabetes

Aims/hypothesisMitochondrial cristae architecture is a key determinant of oxidative capacity in skeletal muscle. While mitochondrial dysfunction is common in type 2 diabetes, it remains unclear whether cristae density is reduced and whether it can be improved by exercise training. We therefore investigated the mitochondrial cristae density in skeletal muscle of patients with type 2 diabetes compared with glucose-tolerant individuals with obesity and lean individuals, and examined the effect of high-intensity interval training (HIIT). MethodsIn a non-randomized intervention study, the effect of an 8-week supervised HIIT intervention combining rowing and cycling was examined in male participants (aged 40-65 years) with type 2 diabetes (n=15), glucose-tolerant individuals with obesity (n=15), and lean individuals (n=18). Muscle biopsies from the m. vastus lateralis were analyzed using transmission electron microscopy (TEM) to quantify mitochondrial cristae density (cristae surface area per mitochondrial volume) and to derive cristae surface area per muscle volume, integrating mitochondrial abundance and ultrastructure. To ensure high stereological precision, a minimum of 49 mitochondrial profiles per sample were analyzed. ResultsNo differences in mitochondrial cristae density were observed between groups at baseline. HIIT induced an [~]7% increase in cristae density across all groups, with the most pronounced adaptations in type 2 fibers and in the intermyofibrillar compartment. At baseline, patients with type 2 diabetes exhibited lower cristae surface area per muscle volume compared with lean individuals. Notably, cristae surface area per muscle volume increased more than mitochondrial volume density alone, reflecting combined structural and volumetric remodeling. Conclusions/interpretationSkeletal muscle mitochondrial cristae density is not different between patients with type 2 diabetes and glucose-tolerant individuals with obesity and lean individuals, and the capacity for cristae remodeling in response to exercise is not affected by type 2 diabetes. These findings highlight the plasticity of mitochondrial architecture and support HIIT as a potent stimulus for improving muscle oxidative and metabolic health, also in type 2 diabetes. Research in Context What is already known about this subject?O_LISkeletal muscle mitochondrial cristae architecture is critical for oxidative phosphorylation and metabolic health. C_LIO_LIType 2 diabetes is associated with altered mitochondrial structure, but whether cristae density is reduced remains unclear. C_LIO_LIPrevious short-term exercise interventions have shown limited or inconsistent effects on mitochondrial cristae density, possibly due to methodological constraints. C_LI What is the key question?O_LICan high-intensity interval training (HIIT) remodel skeletal muscle mitochondrial cristae in patients with type 2 diabetes, and is baseline cristae density altered in this condition? C_LI What are the new findings?O_LIBaseline mitochondrial cristae density does not differ between patients with type 2 diabetes and glucose-tolerant individuals with obesity and lean individuals, but cristae surface area per muscle volume is lower in type 2 diabetes. C_LIO_LIEight weeks of HIIT increased mitochondrial cristae density by [~]7% across all groups, with cristae surface area per muscle volume increasing more than mitochondrial volume density alone. C_LIO_LIExercise-induced cristae remodeling occurs in both muscle fiber types and subcellular compartments, demonstrating preserved structural plasticity in type 2 diabetes. C_LI How might this impact on clinical practice in the foreseeable future?O_LIHIIT represents a potent intervention to improve mitochondrial architecture and potentially enhance muscle oxidative capacity and metabolic health in individuals with type 2 diabetes. C_LI

cell biology↗

bioRxiv2025

Universal principles of protein resource allocation among cellular organelles revealed by yeast large-scale absolute quantitative proteomics

The presence of organelles is a hallmark distinguishing eukarya from bacteria and archaea, and this culminates in compartmentalization of cellular metabolism and subsequent metabolic specialization. Here we established a dataset encompassing over 300 absolute quantitative proteomes, the largest to date, across two yeast species under diverse experimental conditions. Leveraging big data analysis, formula fitting, and machine learning models, quantitative correlations among protein abundance, organelle-level resource distribution, and cellular phenotypes were elucidated at a system level. We found that protein resources always exhibit robust and precise distribution at the organelle level across distinct conditions. Specifically, at high specific growth rates, the protein mass fraction from some main organelles, i.e., peroxisome and nucleus, is consistently reduced to offset the increasing protein resource demand from the ribosome. Meanwhile, we found that the nutrition limitation could induce resource recycling by upregulating protein resources within the vacuole and lipid droplets to sustain stress adaptation. Importantly, our integrative analysis demonstrates that protein mass fraction from less than 4 organelles (e.g., nucleus and ribosomes) can accurately predict diverse yeast physiological parameters (e.g., specific growth rate, oxygen uptake rate), and a core set of 37 proteins could predict resource allocation among 24 main organelles and sub-organelles with high accuracy (average R^2 > 0.9). Finally, we found organelle resource allocation reflects the divergence of yeast species. For example, anaerobic conditions and respiratory suppression have less influence on Crabtree-positive yeast, i.e., Saccharomyces cerevisiae, with respect to organelle resource allocation but have a larger effect on the Crabtree-negative yeast Issatchenkia orientalis, thus suggesting that cellular resources have facilitated adaptive evolution. In summary, the high-quality, genome-scale quantitative proteomic dataset for yeast species offers an unprecedented opportunity for understanding the basic principles underlying resource allocation at the organelle level, laying theoretical foundations for precision engineering of cell factories in synthetic biology. The resource used in this study is available at https://yeast-proteome-database.streamlit.app/.

systems biology↗

bioRxiv2025

Chemogenetic Mitochondrial H2O2 Generation Triggers Dose-Dependent Skeletal Muscle Wasting Signatures

Mitochondrial hydrogen peroxide (mtH2O2) has long been implicated in skeletal muscle atrophy, yet its direct role in vivo has remained unresolved due to methodological constraints. Here, we aimed to establish a chemogenetic platform for precise, compartment-specific induction of mtH2O2 in adult skeletal muscle and to investigate how graded redox stress impacts on muscle proteostasis in vivo. Using mitochondria-targeted D-amino acid oxidase (mtDAAO), we show that prolonged and/or high mtH2O2 exposure progressively activates proteolytic and denervation-associated pathways, culminating in myofiber damage and regeneration. Remarkably, even low exposure to mtH2O2 is sufficient to acutely suppress protein synthesis and induce disuse-like atrophy, without structural damage or overt oxidative stress. This approach provides a powerful in vivo framework to dissect subcellular redox-controlled signaling in muscle and identifies mtH2O2 as a modulator of muscle proteostasis, with therapeutic relevance for muscle-wasting conditions.

molecular biology↗

bioRxiv2025

Metabolomics Ex/GWAS in the Amish reveals novel insights into cardiometabolic disease pathways

We conducted an exome and genome-wide association study (Ex/GWAS) of 1,015 metabolites in serum samples from 5,981 Amish adults. We identified 149 functional or likely functional genetic variants, based on CADD scores significantly associated (P < 5.8 x 10-8) with 519 metabolite levels, 69 of which were >10-fold enriched in the Amish versus Europeans in gnomAD. We discovered novel associations involving a PCK2 splice-donor variant (rs138881435) and metabolites important for energy metabolism and mitochondrial function. In UK Biobank participants, this variant was associated with increased longitudinal relaxation time (T1) values on liver MRI suggesting increased inflammation and fibrosis. Furthermore, we found novel associations involving ENPEP stop-gain variant (rs33966350) and peptide and amino acid metabolite levels, implicating ENPEPs roles in blood pressure regulation. Additional known and novel genetic variant-metabolite associations were identified including genes involved in Amish-enriched Mendelian diseases and cardiometabolic traits, providing insights into underlying mechanisms of these disorders.

genomics↗

bioRxiv2025

AlphaGEM Enables Precise Genome-Scale Metabolic Modelling by Integrating Protein Structure Alignment with deep-learning-based Dark Metabolism Mining

Constructing high-quality genome-scale metabolic models (GEMs) for less-studied species remains challenging. To address this, we developed AlphaGEM, a versatile toolbox leveraging proteome-scale structural alignment and deep-learning-based predictions for efficient genomic mining to generate GEMs ready for applications. Our findings show that the structural alignment or protein-language-model-based prediction (i.e., PLMSearch), could identify more homologous protein relationships than sequence-blast-based alignment, contributing to the accurate profiling of metabolism from target organisms. Additionally, AlphaGEM encompasses an ensemble procedure empowered by multiple deep learning toolboxes to effectively mine the dark metabolic functions encoded by nonhomologous proteins, significantly expanding species-specific metabolic networks. We demonstrate AlphaGEMs accuracy by building GEMs for eukaryotes (e.g., S. pombe, C. albicans) and prokaryotes (e.g., K. pneumoniae, B. subtilis), achieving predictions comparable to manually curated models while outperforming existing tools. AlphaGEM also successfully reconstructs GEMs for M. musculus and C. griseus, showcasing its great potential for uncovering dark metabolism in complex mammals. Lastly, we demonstrate that AlphaGEM could facilitate the automatic GEMs reconstruction for 332 distinct yeast species with high prediction fidelity. In conclusion, AlphaGEM provides unprecedented opportunities for the precise, rapid construction of GEMs across diverse domains, which sets a solid foundation for universal functional analysis of non-model organisms having genome sequences available.

bioinformatics↗

bioRxiv2025

Single-vesicle tracking of α-synuclein oligomers reveals pore formation by a three-stage model modulated by charge, curvature, lipids and ligands

Neurodegenerative disorders like Parkinsons disease (PD) pose significant health challenges. A major hallmark is the aggregation of -synuclein into toxic oligomers (SO) and fibrils. While many efforts focus on slowing disease progression, the molecular origins and mechanisms of SO toxicity remain poorly understood, particularly its proposed link to membrane disruption. To address this, we have developed a single-vesicle analysis platform for direct and real-time measurements of SO and membrane interaction. This allows us to show real-time translocation of dyes through SO pores with single-particle resolution and single-channel electrical recordings for analyzing pore formation in planar lipid bilayers. Across methods, our data reveal evidence for a three-stage model for SO and membrane interactions with initial membrane recruitment followed by partial pore insertion and subsequent full pore formation. Strikingly, while SO recruitment was found to favor curved membranes, pore formation occurred more efficiently in less curved membranes, hence recruitment is divorced from a membrane charge-promoted reorientation and pore integration. Single SO pore formations are undergoing multiple translocation steps hence pore formation is highly dynamic cycling back and forth from partial insertion to full pore formation. The dynamic nature of pore formation can be modulated by lipid charge, lipid headgroup class, and ligand binding. Our findings suggest that increased dynamic pore formation could implies increased membrane toxicity. Evidence for the three-stage model is important for future targeting strategies for blocking SO mitigated PD-related cellular dysfunction and we envision the single-vesicle assay enables screening for ligands modulating the pore formation.

biophysics↗

bioRxiv2025

Increased contact between lipid droplets and mitochondria in skeletal muscles of male elite endurance athletes

Endurance athletes exhibit higher skeletal muscle mitochondrial and lipid droplet (LD) content compared to recreationally active individuals, along with greater whole-body oxygen uptake and maximal fat oxidation rates. In this study, we investigated if these differences manifest in a greater LD-mitochondria contact and how this may relate to the organelles size, shape, and numerical densities. We obtained skeletal muscle biopsies from 17 male elite triathletes and road cyclists and 7 recreationally active men. Using quantitative transmission electron microscopy, we found that the endurance athletes had 2-3-fold greater LD-mitochondria contact length than the recreationally active individuals. This was related to higher numerical densities of both mitochondria and LDs in the intermyofibrillar space. Adding data from untrained individuals with equally high intermyofibrillar LD density as the endurance athletes revealed a 24% greater LD-mitochondria contact length in the endurance athletes. We observed small trivial differences in the shape of both organelles between populations. However, large mitochondrial profiles were more elongated and irregular in shape compared to small mitochondrial profiles, while large LD profiles were more circular and less irregular than small LD profiles. Within the group of athletes, large intermyofibrillar LD profiles correlated with a high fraction of PLIN5-positive LDs and their maximal fat oxidation rate was positively associated with an interaction between the profile size of both intermyofibrillar LDs and mitochondria. In conclusion, male endurance athletes have a greater LD-mitochondria contact than recreationally active and untrained individuals. This muscular phenotype is restricted to the intermyofibrillar space and to fibres rich in mitochondria.

physiology↗

bioRxiv2024

Brown Bears activates a Satiety Hormone Cholecystokinin (CCK) pathway in adipose tissue during hibernation

The brown bear (Ursus arctos) hibernates to survive cold winters without access to food. It builds enormous subcutaneous fat stores during summer and relies on it for energy during winter. Remarkably, the weight loss during winter occurs without muscle loss despite inactivity. Studying brown bear biology can therefore provide insights for improving human health in obesity and weight loss treatments. We here investigate subcutaneous adipose tissue biopsies obtained during summer and winter from free-living brown bears. During winter, a signature of genes involved in food intake and digestion is upregulated. Among these are several regulators of satiety, substrate transport and lipid metabolism. Interestingly, in humans these genes are enriched in distinct metabolic organs including, brain, intestine, stomach, liver and even salivary glands. We focused on the satiety brain/intestinal hormone cholecystokinin (CCK), which we demonstrate is produced in adipocytes, accompanied by an upregulation of the CCK receptor CCKBR. Importantly, CCK was undetectable in the circulation during winter and presence of sensory neurons suggest a neuronal feedback mechanism within the adipose tissue. Using RNA sequencing, we predict additionally 537 secreted proteins to be seasonally regulated, 37 of which could be confirmed with plasma proteomics. In conclusion, we propose that brown bears have developed a strategy of healthy fat burning and satiety regulation through an adipose tissue-contained mechanism which includes digestion factors and satiety mediators to provide safe energy turnover during hibernation-dependent weight loss.

molecular biology↗

bioRxiv2024

Bridging species boundaries: eDNA and genetic analysis reveal hybrid settlement at the very end of American eel distribution

Documenting species distributions and hybridization patterns is paramount for elucidating biogeography and understanding speciation processes. Here we combined genetic specimen analysis and environmental DNA (eDNA) to investigate the presence of American eel (Anguilla rotrata) and American x European eel (Anguilla anguilla) hybrids in Greenland freshwater. We further tested the use of eDNA to document hybridization by using European eel mtDNA as a proxy for hybrid occurrence. Overall, eDNA analysis detected mainly American eel but also European eel mtDNA. This finding was validated by DNA sequencing, which identified 3 out of 26 captured eels (14.3%) carrying European eel mtDNA. Five eels (19.2%), including all three with European mtDNA, were heterozygous for species-specific nuclear gene variants, supporting a hybrid ancestry. Further, eDNA successfully identified eels in lakes where they were caught by fyke net fishing, extending their confirmed northern range by 40 km, and indicated eel presence >200km further north. The study provides an empirical demonstration of the use of eDNA to document hybrid occurrence and extends the reported northern distribution of eels in Greenland significantly beyond previous observations. Further, the existence of hybrid eels in Greenland may be key for understanding the complex mechanisms of hybridization between American and European eels.

genetics↗