Search bioRxiv⌕ Search

Biology subjects

Tong, Q.

Publications and source records attributed to Tong, Q..

17 recordsLinked to original sources

A genetic tool targeting brain GPR75

G-protein-coupled receptor 75 (GPR75) has emerged as an important mediator in diet-induced obesity (DIO) and a promising therapeutic target for anti-obesity drugs. However, the anatomical location of GPR75 in the brain remains unclear, hindering the understanding of GPR75 biology in DIO. Here, we generated a new GPR75-GFP-Ires-Cre knockin mouse strain, in which the Cre expression is driven by the endogenous GPR75 promoter and the GFP is fused with the C-terminal of the GPR75 protein. Both Cre and GFP were confirmed to be colocalized with the endogenous GPR75 expression. In addition, the GPR75-GFP fusion protein remains functionally normal with unaltered susceptibility to DIO. Moreover, using this mouse strain, we found that GPR75 is broadly expressed throughout the brain and mainly localized to the cytoplasm of brain neurons. This new genetic tool can therefore be used to study the neural basis for GPR75 in mediating DIO.

neuroscience↗

An obligatory role for AgRP neurons in maintaining body temperature during time-restricted feeding

Homeotherms maintain a steady body temperature through thermoregulation, a process critical for survival during fasting, in which the brain has to defend energy-costly body temperature while reducing energy expenditure to conserve energy reserve; however, the neural basis for defending body temperature remains unclear. Here, we demonstrated that AgRP neuron lesion led to lethality during time-restricted feeding but no obvious impact on HFD-induced obesity or obesity-reducing responses to glucagon-like peptide-1 receptor agonism. The lesion disrupted adaptive feeding behaviors during time-restricted feeding and reduced motivational feeding. Notably, the lethality was caused by hypothermia instead of reduced food intake. The lesion also caused failure in body temperature maintenance during acute fasting in cold. Fasting-induced activation in AgRP neurons was abrogated when mice were placed in a warm environment. Our results identify the physiological role for AgRP neurons in defending body temperature during restricted feeding but dispensable for body weight regulation with food ad libitum.

neuroscience↗

Non-planar perylene diimides dual-targeting mitochondrial membrane potential and mitochondrial DNA transcription for an-titumor Therapy

Mitochondrial DNA (mtDNA) transcription is an emerging target in cancer therapy. While enzyme-targeted inhibitors such as IMT1B block POLRMT, their organelle specificity remains unclear. Here, we report a distinct strategy using non-planar perylene diimide derivatives (PDIs). The fluorescent lead compound PDIC-BL combines mitochondrial membrane potential ({Delta}{Psi}m) dependent accumulation (validated in cells and isolated mitochondria), and with direct intercalation into mtDNA (Kd = 32 M), as demonstrated by single-molecule stretching assays. This dual-targeting mechanism leads to selective inhibition of mitochondrial transcription, ROS generation and triggers apoptosis. PDIC-BL exhibits superior antitumor efficacy in breast cancer cell lines (MCF-7, MDA-MB-231) and significantly supresses tumor growth in vivo, with good tolerability in cancer xenograft model in nude mice. This work not only elucidates the structure-activity relationship of non-planar PDIs, but also offers a generalizable strategy for developing organelle-selective DNA binding therapeutics.

cancer biology↗

Cytochrome b5 reductase 4 efficiently reduces Neuroglobin and Cytoglobin

Cytoglobin and Neuroglobin are heme-containing proteins expressed in most vertebrates, including mammals, with still not completely defined physiological roles. Most of the putative functions of cytoglobin/neuroglobin, such as oxygen binding or nitric oxide dioxygenation, rely on the heme iron being in the ferrous (Fe2+) oxidation state. Therefore, it is very possible that reducing systems are active in the cell to maintain both proteins in the ferrous state. We have previously shown that the cytochrome b5 reductase isoform 3/ cytochrome b5 system, the canonical reductase of hemoglobin and myoglobin, can reduce cytoglobin at very fast rates, consistent with a possible physiological role. However this reducing system is unable to reduce neuroglobin, which to date lacks a validated, physiologically feasible reducing system. Here we have studied the interaction of cytochrome b5 reductase isoform 4 with cytoglobin and neuroglobin and found that cytochrome b5 reductase 4 can reduce cytoglobin at rates comparable to those observed with cytochrome b5 reductase 3/ cytochrome b5. Remarkably, it can also reduce neuroglobin efficiently. Studying different surface mutations of cytoglobin and neuroglobin we note that some cytoglobin mutations, in particular R84E and K116E decrease reduction rates by more than 10-fold, whereas surface mutations in neuroglobin that were shown to impair the interaction of neuroglobin with cytochrome c (E60K/D73K/E87K) show little effect on the reduction rates. We conclude that cytochrome b5 reductase 4 can supplement cytochrome b5 reductase 3/ cytochrome b5 roles for cytoglobin reduction in vivo and is a strong candidate for a physiological role as neuroglobin reductase.

biochemistry↗

Epistasis and cryptic QTL identified using modified bulk segregant analysis of copper resistance in budding yeast

The contributions of genetic interactions to natural trait variation are challenging to estimate experimentally, as current approaches for detecting epistasis are often underpowered. Powerful mapping approaches such as bulk segregant analysis, wherein individuals with extreme phenotypes are pooled for genotyping, obscure epistasis by averaging over genotype combinations. To accurately characterize and quantify epistasis underlying natural trait variation, we have engineered strains of the budding yeast Saccharomyces cerevisiae to enable crosses where one parents chromosome is fixed while the rest of the chromosomes segregate. These crosses allow us to use bulk segregant analysis to identify quantitative trait loci (QTL) whose effects depend on alleles on the fixed parental chromosome, indicating a genetic interaction with that chromosome. Our method, which we term epic-QTL (for epistatic-with-chromosome QTL) analysis, can thus identify interaction loci with high statistical power. Here we perform epic-QTL analysis of copper resistance with chromosome I or VIII fixed in a cross between divergent naturally derived strains. We find seven loci that interact significantly with chromosome VIII and none that interact with chromosome I, the smallest of the 16 budding yeast chromosomes. Each of the seven interactions alters the magnitude, rather than the direction, of an additive QTL effect. We also show that fixation of one source of variation -- in this case chromosome VIII, which contains the large-effect QTL mapping to CUP1 -- increases power to detect the contributions of other loci to trait differences. Author SummaryMost traits of interest that vary in populations are determined by multiple genetic factors, as well as by environmental variation and random chance. These influences may combine in complicated ways, for example when the effect of one genetic variant depends on genetic variants elsewhere in the genome. Such dependencies are difficult to identify and characterize because testing many possible combinations of influences reduces statistical power. We address this challenge by combining bulk segregant analysis, a robust method for detecting effects of individual genetic variants averaged across genetic backgrounds, with chromosome fixation in budding yeast. This approach allows us to detect gene-variant effects that depend on the fixed chromosome with statistical power comparable to that achieved when detecting background-independent effects. Applying the approach to copper sulfate resistance, we identify and characterize interaction effects and, by removing one source of variation (a single yeast chromosome), improve detection of background-independent effects as well.

genomics↗

CD4+ tissue resident memory Th17 cells drive IL-17A-mediated joint pathology in Spondyloarthritis

ObjectivesInterleukin (IL)-17A is a key driver of Spondyloarthritis (SpA) joint pathology. We aimed to identify its cellular source in synovial tissue from patients with two forms of SpA namely Axial SpA (AxSpA) and Psoriatic arthritis (PsA). MethodsSynovial tissue from patients with SpA was profiled using single-cell RNA sequencing (scRNA-seq: AxSpA, n=5 and PsA, n=6) or spatial RNA profiling (PsA, n=4). CellPhoneDB was used to infer cell-cell communication. Tissue resident memory Th17 (TRM17)-like cells were generated in vitro using blood memory CD4+ T cells from SpA patients. An epigenetic inhibitor library, siRNA and clustered regularly interspaced short palindromic repeats (CRISPR) were used to identify epigenetic regulator(s) for TRM17. ResultsscRNA-seq showed that CD4+CXCR6+ TRM17 cells are the predominant spontaneous IL17A producers in SpA synovium. Cell-cell communication and single-cell spatial analysis support the interaction between TRM17 and CLEC10A+ dendritic cells, which were activated in SpA. Both sublining and lining fibroblasts in SpA synovium showed evidence of IL-17A activation. In vitro-generated CD4+ TRM17-like cells phenocopied joint tissue TRM17, producing IL-17A/F upon T cell receptor (TCR) stimulation, which was further enhanced by cytokines. Perturbation of BRD1 inhibited the generation of TRM17-like cells. ConclusionsCD4+ TRM17 cells are the predominant source of IL-17A in SpA synovial tissue. TCR stimulation is essential for the secretion of IL-17A by CD4+TRM17-like cells. The epigenetic regulator BRD1 contributes to the generation of CD4+TRM17. Depleting CD4+TRM17 cells in SpA is thus a therapeutic strategy with potential to induce long-term remission. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSInterleukin (IL)-17A plays a key role in the immunopathogenesis of Spondyloarthritis (SpA), but its cellular source in joint tissue has not been determined previously. The induction and accumulation of CD4+ tissue resident memory Th17 (TRM17) cells following the clearance of pathogens has been described in skin, lung and kidney. Whether CD4+ TRM17 cells also accumulate in the joint and contribute to the pathology of SpA is not clear. What this study addsO_LICD4+ TRM17 cells are present in SpA synovial tissue and are the predominant source of IL17A C_LIO_LICD4+ TRM17 cells in SpA joints express IL17A without any in vitro exogenous stimulation C_LIO_LIT cell receptor (TCR) rather than cytokine stimulation is essential for IL-17A production by CD4+ TRM17-like cells C_LIO_LIThe epigenetic regulator BRD1 contributes to the generation of CD4+ TRM17-like cells. C_LI How this study might affect research, practice or policyOur findings identify CD4+ TRM17 cells as the primary source of IL-17A in SpA synovium, a previously unrecognized role for these cells. Key questions remain: How do CD4+ TRM17 cells relate to IL-17A producers in synovial fluid? What mechanisms induce and maintain them in the joint? How do they interact with other cells to promote arthritis? These questions warrant further investigation. In addition, our data suggest that targeting CD4+ TRM17 cells, the "factory" of IL-17A in SpA synovial tissue, has the potential to induce long-term remission, encouraging future efforts to develop new therapies to deplete CD4+ TRM17 cells in SpA.

immunology↗

AxSpA joint tissue is characterised by HLA-DR+ tissue resident memory (TRM) and killer cell immunoglobulin-like receptor (KIR)+ CD8+ T cell subsets

ObjectiveAxial Spondyloarthritis (AxSpA) is a common inflammatory arthritis with HLA-B*27 as the major genetic risk. Recent discoveries of AxSpA-specific T cell receptor (TCR) motifs and the self and bacterial peptides that they recognize support a pathogenic role of CD8+ T cells. Despite of previous work on synovial fluid, the characteristics of CD8 cells in joint tissue are currently unknown. MethodSynovial tissues from 5 AxSpA patients were used for single cell RNA sequencing (scRNA-seq). Paired TCR sequencing was carried out for 2. The abundance of KIR+CD8+ T cells in the blood from 9 AxSpA patients and 10 healthy controls was measured using flow cytometry. The expression of naive and memory T cell markers (CCR7, CD45RA and CD45RO) were compared between KIR+ and KIR- CD8 cells. ResultsWe observed conventional, TRAV1-2+ mucosal-associated invariant T (MAIT) cell and MKI67+ proliferating cell populations in synovium. Following sub-clustering of conventional CD8+ T cells, HLA-DR+ tissue resident memory (TRM), circulating, KIR+ and FCGR3A+ (encoding CD16) cell subsets were observed. HLA-DR+ TRM and KIR+ cells were clonally expanded and exhibited distinct transcriptional features, enriched for T cell activation pathways and natural killer (NK) cell-mediated cytotoxicity pathway respectively. Lastly, KIR+CD8+ T cells were increased in AxSpA blood and enriched for CD45RA+CCR7- TEMRA cells. ConclusionHere we present the very first transcriptomic profiling of CD8+ T cells in synovium tissue and highlight potential roles of HLA-DR+ TRM and KIR+ cells in AxSpA pathology. This study adds novel insights to the disease mechanisms and offers new therapeutic opportunities.

immunology↗

RecombiCraft Library construction: A novel method for DNA Library cloning and expansion using non-enzymatic single-step DNA recombination and liquid culture

In this study, we introduce RecombiCraft, an innovative, rapid, and cost-efficient method for constructing DNA libraries in E. coli. This method uses seamless ligation cloning extract (SLiCE) coupled with liquid culture amplification to effectively minimize sequence biases. The technique capitalizes on the natural homologous recombination capabilities of E. coli cell lysates, eliminating the need for multiple purified enzymes and reducing costs. We first synthesized the library backbone and inserts via PCR, employing high-fidelity polymerase to minimize sequence bias. The SLiCE technique was then used to assemble the DNA fragments introduced into E. coli through electroporation. To ensure the integrity of the library, we optimized culture times based on next-generation sequencing analysis which confirmed the minimal sequence bias. The RecombiCraft method demonstrates that this approach is economical and maintains the librarys uniformity. It is a promising tool for genetic research and biotechnological applications with a significantly shorter library generation period.

molecular biology↗

5-HT Neurons Integrate GABA and Dopamine Inputs to Regulate Meal Initiation

Obesity is a growing global health epidemic with limited effective therapeutics. Serotonin (5-HT) is one major neurotransmitter which remains an excellent target for new weight-loss therapies, but there remains a gap in knowledge on the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using a closed-loop optogenetic feeding paradigm, we showed that the 5-HTDRN{lozenge}arcuate nucleus (ARH) circuit plays an important role in regulating meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response to GABAergic inputs can be enhanced by hunger. Additionally, deletion of the GABAA receptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process. Finally, we identified the instrumental role of dopaminergic inputs via dopamine receptor D2 in 5-HTDRN neurons in enhancing the response to GABA-induced feeding. Thus, our results indicate that 5-HTDRN neurons are inhibited by synergistic inhibitory actions of GABA and dopamine, which allows for the initiation of a meal.

neuroscience↗

Tuning Collective Behaviour in Zebrafish with Genetic Modification

Zebrafish collective behaviour is widely used to assess their physical and mental state, serving as a valuable tool to assess the impact of ageing, disease genetics, and the effect of drugs. The essence of these macroscopic phenomena can be represented by active matter models, where the individuals are abstracted as interactive self-propelling agents. The behaviour of these agents depends on a set of parameters in a manner reminiscent of those between the constituents of physical systems. In a few cases, the system may be controlled at the level of the individual constituents such as the interactions between colloidal particles, or the enzymatic behaviour of de novo proteins. Usually, however, while the collective behaviour may be influenced by environmental factors, it typically cannot be changed at will. Here, we challenge this scenario in a biological context by genetically modifying zebrafish. We thus demonstrate the potential of genetic modification in the context of controlling the collective behaviour of biological active matter systems at the level of the constituents, rather than externally. In particular, we probe the effect of the lack of col11a2 gene in zebrafish, which causes the early onset of osteoarthritis. The resulting col11a2 -/- zebrafish exhibited compromised vertebral column properties, bent their body less while swimming, and took longer to change their orientations. Surprisingly, a group of 25 mutant fish exhibited more orderly collective motion than the wildtype. We show that the collective behaviour of wildtype and col11a2 -/- zebrafish are captured with a simple active matter model, in which the mutant fish are modelled by self-propelling agents with a higher orientational noise on average. In this way, we demonstrate the possibility of tuning a biological system, changing the state space it occupies when interpreted with a simple active matter model.

animal behavior and cognition↗

SACNet: A Multiscale Diffeomorphic Convolutional Registration Network with Prior Neuroanatomical Constraints for Flexible Susceptibility Artifact Correction in Echo Planar Imaging

Susceptibility artifacts (SAs), inevitable in brain diffusion MR (dMRI) scans acquired using single-shot echo planar imaging (EPI), severely compromise the accurate detection of human brain structure. Existing SA correction (SAC) methods offer inadequate correction quality and limited applicability across diverse datasets with varied acquisition protocols. To address these challenges, we proposed SACNet, a SAC framework based on unsupervised registration convolutional networks, featuring: i) a novel diffeomorphism regularization function to avoid unnatural SAC warps, modified from a potential well function; ii) an integration with prior neuroanatomical constraints and coarse-to-fine processing strategy to enables multi-scale geometric and intensity recoveries in severe distorted areas; iii) a unified registration framework that incorporates multiple phase-encoding (PE) EPI images and structural images, ensuring compatibility with both single- and inverse-PE protocols, with or without field maps. Utilizing simulated dMRI images and over 2000 brain scans from neonatal, child, adult and traveling participants, our method consistently demonstrates state-of-the-art correction performance. Notably, SACNet effectively reduces SAs-related multicenter effects compared to existing methods. We have developed user-friendly tools using containerization techniques, hope to facilitate SAC correction quality across extensive neuroimaging studies.

neuroscience↗

An Excitatory Projection from the Basal Forebrain to the Ventral Tegmental Area Underlying Anorexia-like Phenotypes

Adaptation to potential threat cues in feeding regulation is key for animal survival. Maladaptation in balancing internal energy needs and external threat cues may result in eating disorders. However, brain mechanisms underlying such maladaptation remain elusive. Here, we identified that the basal forebrain (BF) sends glutamatergic projections to glutamatergic neurons in the ventral tegmental area (VTA). Glutamatergic neurons in both the BF and the VTA displayed correlated responses to various external stressors. Notably, in vivo manipulation of BF terminals in the VTA revealed that the glutamatergic BFVTA circuit reduces appetite, increases locomotion, and elicits avoidance. In consistence, activation of VTA glutamatergic neurons reduced body weight, blunted food motivation, and caused hyperactivity with behavioral signs of anxiety, all hallmarks of typical anorexia phenotypes. Importantly, activation of BF glutamatergic terminals in the VTA reduced dopamine release in the nucleus accumbens (NAc). Collectively, our results point to overactivation of the glutamatergic BFVTA circuit as a potential cause of anorexia-like phenotypes involving reduced dopamine release.

neuroscience↗

Increased public health threat of avian-origin H3N2 influenza virus during evolution in dogs

Influenza A viruses in animal reservoirs repeatedly cross species barrier to infect humans. Once an animal-borne virus with novel antigenicity acquired the efficient human to human transmissibility, it will become epidemic in the population. Dogs are the closest animal companions to humans and canine respiratory tract expresses both SA2,3-(avian type) and 2,6-Gal (human type) receptors. However, the role of dogs in the ecology of influenza viruses is unclear. H3N2 avian influenza viruses transmitted to dogs around 2006 and have formed stable lineages. The long-term epidemic of avian-origin H3N2 virus in canine offers the best models to investigate the effect of dogs on the evolution of influenza viruses. Here, we carried out a systematic and comparative identification of the biological characteristics of H3N2 canine influenza viruses (CIVs) isolated in the worldwide over 10 years. We found that during the adaptation of H3N2 CIVs to dogs, H3N2 CIVs became to recognize the human-like SA2,6-Gal receptor, gradually increased HA acid stability and replication ability in human airway epithelial cells, and acquired a 100% transmission rate via respiratory droplet in ferret model, which were essential hallmarks of being adapted to humans. We also identified that the frequency of substitutions related to human adaptation has gradually increased in H3N2 CIVs, and determined four cumulative molecular changes responsible for the increased airborne transmission ability in ferrets. Our results suggested that canine may serve as an intermediate for the adaptation of avian influenza virus to human. Continuous surveillance coordinated with risk assessment for CIVs is necessary.

microbiology↗

A deep learning-based multisite neuroimage harmonization framework established with traveling-subject dataset

The accumulation of multisite large-sample MRI datasets collected by large brain research projects in the last decade has provided a critical resource for understanding the neurobiological mechanisms underlying cognitive functions and brain disorders. However, the significant site effects, observed in the imaging data and their derived structural and functional features, has prevented the derivation of consistent findings across different studies. The development of harmonization methods that can effectively eliminate complex site effects while maintaining biological characteristics in neuroimaging data has become a vital and urgent requirement for multisite imaging studies. Here, we proposed a deep learning-based framework to harmonize imaging data from pairs of sites, in which site factors and brain features can be disentangled and encoded. We trained the proposed framework with a publicly available traveling-subject dataset from SRPBS and harmonized the gray matter volume maps from eight source sites to a target site. The proposed framework significantly eliminated inter-site differences in gray matter volume. The embedded encoders successfully captured both the abstract texture of site factors and the concrete brain features. Moreover, the proposed framework exhibited outstanding performance relative to conventional statistical harmonization methods in site effect removal, data distribution homogenization, and intra-subject similarity improvement. Together, the proposed method offers a powerful and interpretable deep learning-based harmonization framework for multisite neuroimaging data that could enhance reliability and reproducibility in multisite studies for brain development and brain disorders.

neuroscience↗

Adipocyte-Specific Ablation Of PU.1 Promotes Energy Expenditure and Ameliorates Metabolic Syndrome In Aging Mice

ObjectiveAlthough PU.1/Spi1 is known as a master regulator for macrophage development and function, we have reported previously that it is also expressed in adipocytes and is transcriptionally induced in obesity. Here, we investigated the role of adipocyte PU.1 in the development of age-associated metabolic syndrome. MethodsWe generated mice with adipocyte specific PU.1 knockout, assessed metabolic changes in young and aged PU.1fl/fl (control) and AdipoqCre PU.1fl/fl(aPU.1KO) mice, including body weight, body composition, energy expenditure and glucose homeostasis. We also performed transcriptional analyses using RNA-Sequencing of adipocytes from these mice. ResultsaPU.1KO mice have elevated energy expenditure at a young age and decreased adiposity and increased insulin sensitivity in later life. Corroborating these observations, transcriptional network analysis indicated the existence of validated, aPU.1-modulated regulatory hubs that direct inflammatory and thermogenic gene expression programs. ConclusionsOur data provide evidence for a previously uncharacterized role of PU.1 in the development of age-associated obesity and insulin resistance.

cell biology↗

The transcriptome of regenerating zebrafish scales identifies genes involved in human bone disease

Zebrafish scales are mineralised plates that can regenerate involving de novo bone formation. This presents an opportunity to uncover genes and pathways relevant to human musculoskeletal disease relevant to impaired bone formation. To investigate this hypothesis, we defined transcriptomic profiles of ontogenetic and regenerating scales, and identified 604 differentially expressed genes (DEGs) that were enriched for extracellular matrix, ossification, and cell adhesion pathways. Next, we showed that human orthologues of DEGs were 2.8 times more likely to cause human monogenic skeletal diseases (P<8x10-11), and they showed enrichment for human orthologues associated with polygenetic disease traits including stature, bone density and osteoarthritis (P<0.005). Finally, zebrafish mutants of two human orthologues that were robustly associated with height and osteoarthritis (COL11A2) or bone density only (SPP1) developed skeletal abnormalities consistent with our genetic association studies. Col11a2Y228X/Y228X mutants showed endoskeletal features consistent with abnormal growth and osteoarthritis, whereas spp1P160X/P160X mutants had elevated bone density (P<0.05). In summary, we show that transcriptomic studies of regenerating zebrafish scales have potential to identify new genes and pathways relevant to human skeletal disease.

genetics↗

Transient Overexpression of VEGF-A in Adipose Tissue Promotes Energy Expenditure via Activation of the Sympathetic Nervous System

Adipose-derived VEGF-A stimulates functional blood vessel formation in obese fat pads which in turn facilitates healthy expansion of the adipose tissue. However, the detailed mechanism(s) governing the process remains largely unknown. Here, we investigated the role of sympathetic nervous system activation in the process. To this end, we induced overexpression of VEGF-A in an adipose-specific doxycycline (Dox)-inducible transgenic mouse model for a short period of time during high fat-diet (HFD) feeding. We found that local overexpression of VEGF-A in adipose tissue stimulated lipolysis and browning rapidly after Dox induction. Immunofluorescent staining against tyrosine hydroxylase (TH) indicated higher levels of sympathetic innervation in adipose tissue of transgenic mice. In response to the increased norepinephrine (NE) level, expression of {beta}3-andrenoceptor was significantly upregulated and the downstream protein kinase A (PKA) pathway was activated, as indicated by the enhanced phosphorylation of the whole PKA substrates, in particular the hormone sensitive lipase (HSL) in adipocytes. As the result, the adipose tissue exhibited increased lipolysis, browning, and energy expenditure. Importantly, all these effects were abolished upon the treatment with {beta}3-adrenoceptor antagonist SR59230A. Collectively, these results demonstrate that transient overexpressed VEGF-A activates sympathetic nervous system which hence promotes lipolysis and browning in adipose tissue.

physiology↗