Biology subjects

Yang, Y.

Publications and source records attributed to Yang, Y..

At least 631 records · Page 35Linked to original sources

bioRxiv2024

Non-invasive and painless mid-infrared modulation increases collagen in human and mouse skin

Stimulating collagen production in skin helps to enhance vitality while decelerating aging- associated processes in skin tissue. However, current approaches to enhancing collagen production are commonly limited by accompanying pain and trauma. Here, we report that mid-infrared modulation (MIMO) at an intensity of 70 mW/cm2 promotes collagen production in human or mouse skin in vivo without generating excessive heat. We found that protein levels of the collagen- degrading endopeptidase, MMP-1, were decreased in the skin of mice following MIMO treatment, whereas the collagen synthesis-related factors, TGF-{beta}, HSP47, and HSP70, were all increased. In addition, MIMO stimulated collagen secretion in human dermal fibroblasts in vitro. This work demonstrates that MIMO is an effective, non-invasive, and painless intervention for in vivo enhancement of collagen production in the skin. One Sentence SummaryMid-infrared modulation promotes collagen production

molecular biology↗

bioRxiv2024

Indiscriminate activities of different Henipavirus polymerase complex proteins allow for efficient minigenome replication in hybrid systems

The henipaviruses, including Nipah virus (NiV) and Hendra virus (HeV), are biosafety level 4 (BSL-4) zoonotic pathogens that cause severe neurological and respiratory disease in humans. To study the replication machinery of these viruses we developed robust minigenome systems that can be safely used in BSL-2 conditions. The nucleocapsid (N), phosphoprotein (P), and large protein (L) of henipaviruses are critical elements of their replication machinery and thus essential support components of the minigenome systems. Here, we tested the effects of diverse combinations of the replication support proteins on the replication capacity of the NiV and HeV minigenomes by exchanging the helper plasmids coding for these proteins among the two viruses. We demonstrate that all combinations including one or more heterologous proteins were capable of replicating both the NiV and HeV minigenomes. Sequence alignment showed identities of 92% for the N protein, 67% for P, and 87% for L. Notably, variations in amino acid residues were not concentrated in the N-P and P-L interacting regions implying that dissimilarities in amino acid composition among NiV and HeV polymerase complex proteins may not impact their interactions. The observed indiscriminate activity of NiV and HeV polymerase complex proteins is different from related viruses, which can support replication of heterologous genomes only when the whole polymerase complex belongs to the same virus. This newly observed promiscuous property of the henipavirus polymerase complex proteins could potentially be harnessed to develop universal anti-henipavirus antivirals. IMPORTANCEGiven the severity of disease induced by Hendra and Nipah viruses in humans and the continuous emergence of new henipaviruses as well as henipa-like viruses, it is necessary to conduct more comprehensive investigation of the biology of henipaviruses and their interaction with the host. The replication of henipaviruses and the development of antiviral agents can be studied in systems that allow experiments to be performed under biosafety level 2 conditions. Here, we developed two robust minigenome systems for Nipah virus (NiV) and Hendra virus (HeV) that provide a convenient alternative system for studying NiV and HeV replication. Using these systems, we demonstrate that any combinations of the three polymerase complex proteins of NiV and HeV could effectively initiate the replication of both viral minigenomes, which suggest that the interaction regions of the polymerase complex proteins could be effective targets for universal and effective anti-henipavirus interventions.

microbiology↗

bioRxiv2024

CircRNA-Pro: A Novel Toolkit for High-Precision Detection of Differentially Expressed Circular RNAs and Translatable Circular RNAs

With the increasing discovery of circular RNAs (circRNAs) and their critical roles in gene regulation and disease progression, there is a growing need for more accurate and efficient tools for circRNAs research. In response, we have developed an integrated software suite specifically for circRNAs. This all-in-one tool specializes in detecting differentially expressed circRNAs, including those with the potential to be translated into proteins, and allows for comparing against relevant databases, thereby enabling comprehensive circRNA profiling and annotation. To enhance the accuracy in detecting differentially expressed circRNAs, we incorporated three different software algorithms and cross-validated their results through mutual verification. Additionally, this toolkit improves the effectiveness in identifying translatable circRNAs by optimizing Ribo-seq alignment and verifying against public circRNA databases. The performance of circRNA-pro has been evaluated through its application to public RNA-seq and Ribo-seq datasets on breast cancer and SARS-CoV-2 infected cells, and the results obtained have been validated against previous literature and databases. Overall, our integrated toolkit provides a reliable workflow for circRNA research, facilitating insights into their diverse roles across life sciences.

bioinformatics↗

bioRxiv2024

PIGOME: An Integrated and Comprehensive Multi-omics Database for Pig Functional Genomics Studies

In addition to being a major source of animal protein, pigs are important model for the study of development and diseases in humans. During the past two decades, thousands of high-throughput sequencing studies in pigs have been performed using a variety of tissues from different breeds and developmental stages. However, the multi-omics database specifically used for pig functional genomic research is still limited. Here, we present a user-friendly database of pig multi-omics named PIGOME. PIGOME contains seven types of pig omics datasets, including whole-genome sequencing, RNA-seq, miRNA-seq, ChIP-seq, ATAC-seq, bisulfite-seq, and MeRIP-seq, from 6,901 samples and 392 projects with manually curated metadata, integrated gene annotation, and quantitative trait locus information. Furthermore, various explore and browse functions have been established for user-friendly access to omics information. PIGOME implemented several tools to visualize genomic variants, gene expression, and epigenetic signals of a given gene in the pig genome, enabling efficient exploration of spatial-temporal expression/epigenetic pattern, function, regulatory mechanism, and associated economic traits. Collectively, PIGOME provides valuable resources for pig breeding and is helpful for human biomedical research. PIGOME is available at https://pigome.com.

bioinformatics↗

bioRxiv2024

The heritability and structural correlates of brain entropy

Brain entropy (BEN) quantifies the temporal complexity of spontaneous neural activity, which has been increasingly recognized as providing important insights into cognitive functions and psychiatric disorders. However, its heritability and structural underpinnings are not well understood. Here, we utilize sample entropy to calculate BEN in healthy young adults using resting-state fMRI from the Human Connectome Project. We show that BEN is significantly heritable in broad brain regions. Heritability estimates exhibit regional variability, with lower heritability in the limbic and subcortical networks than in other networks. We further relate BEN to structural features including surface area (SA), cortical myelination (CM), cortical thickness (CT), and subcortical volumes (SV). We find that BEN is negatively correlated with SA in most cortical regions, but is positively correlated with CM in the prefrontal cortex, lateral temporal lobe, precuneus, lateral parietal cortex, and cingulate cortex. Only a few cortical regions show significant correlations between BEN and CT. By decomposing correlations into genetic and environmental components, we observe that most of BEN-SA correlations are associated with shared genetic and environmental effects. BEN-CM correlations are mainly attributed to shared environmental effects. BEN-CT correlations are partly related to shared environmental effects. We find no significant associations between BEN and SV. Collectively, our work establishes the genetic basis and structural correlates of resting-state fMRI-based BEN, supporting its potential application as an endophenotype for psychiatric disorders.

neuroscience↗

bioRxiv2024

Spatially conserved pathoprotein profiling in the human suprachiasmatic nucleus in progressive Alzheimer disease stages

Individuals with Alzheimers Disease (AD) experience circadian rhythm disorder. The circadian rhythm is synchronized by a master clock, the suprachiasmatic nucleus (SCN), which is a tiny hypothalamic nucleus. Little is known about the molecular and pathological changes that occur in the SCN during AD progression. We examined postmortem brains of 12 controls without AD neuropathological changes (Braak stage 0) and 36 subjects at progressive Braak stages (I, II, and VI). To investigate potential AD-specific changes, we measured the neuronal counts of arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) positive neurons, along with the Braak stages in the SCN. We investigated in adjacent hypothalamic nuclei which are also composed of AVP+ neurons but show more resilience to AD: paraventricular nucleus (PVN) and supraoptic nucleus (SON). To understand the dysregulated proteins associated to AD progression, we performed in-situ proteomics, investigating 57 proteins, including commonly dysregulated in AD, using GeoMx Digital Spatial Profiling (DSP) in the three nuclei (total of 703 area of interests). Neurofibrillary tangles (NFTs) and tau fibrils were found selectively in SCN. We failed to detect NFTs in SON, only a mild dysregulation of p-tau at Braak VI in PVN and SON. Amyloid plaque was absent in the SCN and SON. Additionally, the SCN showed increased glial proteins already at Braak stage I, whereas the level of these proteins sustained in the other nuclei. The SCN is exclusively vulnerable to AD-tau pathology and show immune dysregulation even at Braak I but is protected against amyloid plaque. This finding revealed selectively in amnestic AD, showing more resilience in AD variant. This tau-related molecular dysregulation in the SCN contributes to circadian rhythm disturbances in AD, a phenomenon observed before the onset of cognitive disorder.

neuroscience↗

bioRxiv2024

Labeling Natural Killer cells with superparamagnetic iron oxide nanoparticles for detection by preclinical and clinical-scale magnetic particle imaging

IntroductionClinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) for the detection, localization, and quantification of VivoTrax-labeled NK cells. MethodsHuman-derived NK-92 cells were labeled by co-incubation with VivoTrax for 24 hours then the excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled vs. unlabeled NK-92 cells was assessed after 4 hours of co- incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17) using bioluminescent or GFP counts. Labeled NK-92 cells at two different doses (0.5 or 1 x 106) were administered to excised mouse brains (cerebellum), tibias, and lungs then imaged by 3D preclinical MPI (MOMENTUM imager) and localized relative to fiducial markers. NK-92 cells were imaged by clinical-scale MPI under development at Magnetic Insight Inc. ResultsNK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measured effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of VivoTrax-labeled NK-92 cells, with preclinical limit of detection of 3.1 x 104 cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, tibias, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection of a clinically relevant dose of 4 x 107 labeled NK-92 cells was demonstrated on clinical-scale MPI. ConclusionMPI can provide sensitive, quantitative, and accurate spatial information on NK cell delivery, showing its potential to resolve a significant unmet clinical need to track NK cell treatments in patients.

biophysics↗

bioRxiv2024

Glioma-associated fibroblasts promote glioblastoma resistance to temozolomide through CCL2-CCR2 paracrine signaling

Complicated tumor microenvironment contributes mostly to chemoresistance in glioblastoma. Glioma-associated fibroblasts (GAFs) were recently identified as non-tumor stromal cells in the glioblastoma microenvironment, whereas their function in glioblastoma chemoresistance is unclear. Herein, we interrogated the correlation between GAFs and chemoresistance of glioblastoma by examining a series of patient-derived GAFs and glioblastoma organoids (GBOs), revealing that GAFs could promote temozolomide resistance in glioblastoma. Mechanistically, C-C motif chemokine ligand 2 (CCL2) secreted by GAFs selectively activated the ERK1/2 signaling in glioblastoma cells to potentiate temozolomide resistance. Pharmacologically disrupting the CCL2-CCR2 axis or MEK1/2-ERK1/2 pathway effectively improved the therapeutic efficacy of temozolomide in GBM cells and patient-derived GBOs, and both decreased phospho-ERK1/2 expression. Collectively, our results identified that targeting the GAF-dominated CCL2-ERK1/2 pathway may be an alternative strategy to alleviate the GAF-mediated chemoresistance of glioblastoma. SignificanceComprehensive interpretation of the mutual support between tumor microenvironment and cancer cells is demanded for glioma with poor response rates to chemotherapy. This study demonstrates that GAFs promote the temozolomide resistance of glioblastoma by secreting cytokine CCL2 to activate ERK1/2 pathway, which may serve as a potential druggable candidate. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/581575v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@167b955org.highwire.dtl.DTLVardef@b892bcorg.highwire.dtl.DTLVardef@1a9b082org.highwire.dtl.DTLVardef@18327a8_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphic abstract.C_FLOATNO Schematic illustration for GAFs mediated chemoresistance of GBMs and underlying mechanisms. We demonstrate that Glioma-associated Fibroblasts (GAFs) grow in gliomas by isolating and identifying a panel of patient-derived GAFs. CCL2 secreted by GAFs stimulates CCR2 in GBM cells, which promotes activation of the ERK1/2 expression to potentiate GBM chemoresistance. C_FIG

cancer biology↗

bioRxiv2024

Chrom-pro: A User-Friendly Toolkit for De-novo Chromosome Assembly and Genomic Analysis

Chromosome-level genome assembly is fundamental to current genomic and post-genomic research, however, the process remains complicated and challenging due to the lack of a standardized automatic workflow. The frequently-used method for high-quality genome assembly generally employs second-generation sequencing (SGS) low error reads, third-generation sequencing (TGS) long reads and Hi-C reads. In this study, we developed a multifunctional toolkit called Chrom-pro that integrated commonly-used algorithms for de novo chromosome-level genome assembly with above three data sets into a user-friendly, automatic workflow. Besides chromosome assembly, Chrom-pro also encompasses multiple functionalities for genome quality assessment, comparative genomic analysis, and structural variant detection, which offers substantial support for downstream research. To evaluate the performance of Chrom-pro software, we tested the software with publicly available sequencing data of mango, pufferfish, and plum, and the excellence was confirmed by achieving a BUSCO completeness score of over 95% as well as high collinearity with the reference genome. Furthermore, we applied Chrom-pro to investigating the impact of different internal algorithm options on the accuracy of chromosome assembly, providing guidance for advancing relevant research in the future. Overall, the development of Chrom-pro will significantly improve the efficiency and quality of chromosome assembly and contributing to the advancement of genomic research.

bioinformatics↗

bioRxiv2024

Decoding the spatiotemporal dynamic neural representation of repetitive facial expression imitation

Imitating facial emotion expressions can facilitate social interactions, although the behavioral and neural spatiotemporal dynamics is unclear. Here participants (N=100) imitated facial emotions repeatedly over one month (16 times in total) with neural activity measured on three occasions using functional near-infrared spectroscopy. Additionally, the transfer effect of repeated imitation on emotional face and scene perception was assessed by fMRI with multivariate pattern analysis. Valence specific imitation performance was facilitated by the alterations in the similarity of spatiotemporal patterns evoked in the mirror neuron system (MNS) with information flow moving progressively towards the inferior frontal gyrus as the as the number of times of imitation increase. Furthermore, MNS representation predictive patterns of processing emotional faces, but not scenes, were enhanced. Overall, these findings provide a neural changes of information flow within MNS and advance our understanding of the spatiotemporal dynamics from novice to proficient of facial emotion imitation.

neuroscience↗

bioRxiv2024

PathEX: Make Good Choice for Whole Slide Image Extraction

BackgroundThe tile-based approach has been widely used for slide-level predictions in whole slide image (WSI) analysis. However, the irregular shapes and variable dimensions of tumor regions pose challenges for the process. To address this issue, we proposed PathEX, a framework that integrates intersection over tile (IoT) and background over tile (BoT) algorithms to extract tile images around boundaries of annotated regions while excluding the blank tile images within these regions. MethodsWe developed PathEX, which incorporated IoT and BoT into tile extraction, for training a classification model in CAM (239 WSIs) and PAIP (40 WSIs) datasets. By adjusting the IoT and BoT parameters, we generated eight training sets and corresponding models for each dataset. The performance of PathEX was assessed on the testing set comprising 13,076 tile images from 48 WSIs of CAM dataset and 6,391 tile images from 10 WSIs of PAIP dataset. ResultsPathEX could extract tile images around boundaries of annotated region differently by adjusting the IoT parameter, while exclusion of blank tile images within annotated regions achieved by setting the BoT parameter. As adjusting IoT from 0.1 to 1.0, and 1 - BoT from 0.0 to 0.5, we got 8 train sets. Experimentation revealed that set C demonstrates potential as the most optimal candidate. Nevertheless, a combination of IoT values ranging from 0.2 to 0.5 and 1-BoT values ranging from 0.2 to 0.5 also yielded favorable outcomes. ConclusionsIn this study, we proposed PathEX, a framework that integrates IoT and BoT algorithms for tile image extraction at the boundaries of annotated regions while excluding blank tiles within these regions. Researchers can conveniently set the thresholds for IoT and BoT to facilitate tile image extraction in their own studies. The insights gained from this research provide valuable guidance for tile image extraction in digital pathology applications.

pathology↗

bioRxiv2024

Biallelic pathogenic variants in DNAH3 cause male infertility in humans and mice

Axonemal protein complexes, including the outer and inner dynein arms (ODA/IDA), are highly ordered structures of the sperm flagella that drive sperm motility. Deficiencies in several axonemal proteins have been associated with male infertility, which is characterized by asthenozoospermia or asthenoteratozoospermia. Dynein axonemal heavy chain 3 (DNAH3) resides in the IDA and is highly expressed in the testis. However, the relationship between DNAH3 and male infertility is still unclear. Herein, we identified biallelic variants of DNAH3 in four unrelated Han Chinese infertile men with asthenoteratozoospermia through whole-exome sequencing (WES). These variants contributed to deficient DNAH3 expression in the patients sperm flagella. Importantly, the patients represented the anomalous sperm flagellar morphology, and the flagellar ultrastructure was severely disrupted. Intriguingly, Dnah3 knockout (KO) male mice were also infertile, especially showing the severe reduction in sperm movement with the abnormal IDA and mitochondrion structure. Mechanically, nonfunctional DNAH3 expression resulted in decreased expression of IDA-associated proteins in the spermatozoa flagella of patients and KO mice, including DNAH1, DNAH6, and DNALI1, the deletion of which has been involved in disruption of sperm motility. Moreover, the infertility of patients with DNAH3 variants and Dnah3 KO mice could be rescued by intracytoplasmic sperm injection (ICSI) treatment. Our findings indicated that DNAH3 is a novel pathogenic gene for asthenoteratozoospermia and may further contribute to the diagnosis, genetic counseling, and prognosis of male infertility.

genetics↗

bioRxiv2024

CRM1 regulates androgen receptor stability and impacts DNA repair pathways in prostate cancer, independent of the androgen receptor.

Among the known nuclear exportins, CRM1 is the most studied prototype. Dysregulation of CRM1 occurs in many cancers, hence, understanding the role of CRM1 in cancer can help in developing synergistic therapeutics. The study investigates how CRM1 affects prostate cancer growth and survival. It examines the role of CRM1 in regulating androgen receptor (AR) and DNA repair in prostate cancer. Our findings reveal that CRM1 influences AR mRNA and protein stability, leading to a loss of AR protein upon CRM1 inhibition. Furthermore, it highlights the involvement of HSP90 alpha, a known AR chaperone, in the CRM1-dependent regulation of AR protein stability. The combination of CRM1 inhibition with an HSP90 inhibitor demonstrates potent effects on decreasing prostate cancer cell growth and survival. The study further explores the influence of CRM1 on DNA repair proteins and proposes a strategy of combining CRM1 inhibitors with DNA repair pathway inhibitors to decrease prostate cancer growth. Overall, the findings suggest that CRM1 plays a crucial role in prostate cancer growth, and a combination of inhibitors targeting CRM1 and DNA repair pathways could be a promising therapeutic strategy.

cancer biology↗

bioRxiv2024

TLR9 activation in large wound induces tissue repair and hair follicle regeneration via gamma delta T cells

The mechanisms underlying tissue repair in response to damage have been one of main subjects of investigation. In this study, we leveraged the wound-induced hair neogenesis (WIHN) models in adult mice to explore the inner correlation. Our investigation revealed that heightened release of mitochondrial DNA (mtDNA) accompanying tissue damage activated the toll-like receptor 9 (TLR9) pathway, influencing the repair process and the ultimate number of regenerated hair follicles. Furthermore, our analysis of single-cell RNA sequencing comparisons demonstrated increased TLR9 activation was associated with the recruitment of gamma delta T cells ({gamma}{delta}T). Inhibition of {gamma}{delta}T cell recruitment led to a reduction in the population of {gamma}{delta}T cells and a more fibrotic healing outcome. Notably, these {gamma}{delta}T cells exhibited distinctive high production of AREG, contributing to the rapid increase of local AREG levels around the epidermis and influencing the fate commitment of keratinocytes. These findings provide new insights into the roles of TLRs as critical mediators in the sense of tissue damage, the modulation of immune cell activity, and the ultimate influence on healing outcomes. TeaserStarting with how tissue injury stimulates downstream tissue repair and regeneration through relevant signals, this study explored the phenomenon and correlation between tissue damage and TLR9, and the effect of TLR9 on {gamma}{delta}T, keratinocytes and the healing outcomes.

cell biology↗

bioRxiv2024

Thyroid Hormone Suppresses Medulloblastoma Progression Through Promoting Terminal Differentiation of Tumor Cells

Hypothyroidism is commonly detected in patients with medulloblastoma (MB). A possible link between thyroid hormone (TH) signaling and MB pathogenicity has not been reported. Here, we find that TH plays a critical role in promoting tumor cell differentiation. Reduction in TH levels frees the TH receptor, TR1, to bind to EZH2 and repress expression of NeuroD1, a transcription factor that drives tumor cell differentiation. Increased TH reverses EZH2-mediated repression of NeuroD1 by abrogating the binding of EZH2 and TR1, thereby stimulating tumor cell differentiation and reducing MB growth. Importantly, TH-induced differentiation of tumor cells is not restricted by the molecular subgroup of MB. These findings establish an unprecedented association between TH signaling and MB pathogenicity, providing solid evidence for TH as a promising modality for MB treatment.

cancer biology↗

bioRxiv2024

Interpretable Drug Response Prediction through Molecule Structure-aware and Knowledge-Guided Visible Neural Network

Precise prediction of anti-cancer drug responses has become a crucial obstruction in anti-cancer drug design and clinical applications. In recent years, various deep learning methods have been applied to drug response prediction and become more accurate. However, they are still criticized as being non-transparent. To offer reliable drug response prediction in real-world applications, there is still a pressing demand to develop a model with high predictive performance as well as interpretability. In this study, we propose DrugVNN, an end-to-end interpretable drug response prediction framework, which extracts gene features of cell lines through a knowledge-guided visible neural network (VNN), and learns drug representation through a node-edge communicative message passing network (CMPNN). Additionally, between these two networks, a novel drug-aware gene attention gate is designed to direct the drug representation to VNN to simulate the effects of drugs. By evaluating on the GDSC dataset, DrugVNN achieved state-of-the-art performance. Moreover, DrugVNN can identify active genes and relevant signaling pathways for specific drug-cell line pairs with supporting evidence in the literature, implying the interpretability of our model.

bioinformatics↗

bioRxiv2024

ChineseEEG: A Chinese Linguistic Corpora EEG Dataset for Semantic Alignment and Neural Decoding

An Electroencephalography (EEG) dataset utilizing rich text stimuli can advance the understanding of how the brain encodes semantic information and contribute to semantic decoding in brain-computer interface (BCI). Addressing the scarcity of EEG datasets featuring Chinese linguistic stimuli, we present the ChineseEEG dataset, a high-density EEG dataset complemented by simultaneous eye-tracking recordings. This dataset was compiled while 10 participants silently read approximately 11 hours of Chinese text from two well-known novels. This dataset provides long-duration EEG recordings, along with pre-processed EEG sensor-level data and semantic embeddings of reading materials extracted by a pre-trained natural language processing (NLP) model. As a pilot EEG dataset derived from natural Chinese linguistic stimuli, ChineseEEG can significantly support research across neuroscience, NLP, and linguistics. It establishes a benchmark dataset for Chinese semantic decoding, aids in the development of BCIs, and facilitates the exploration of alignment between large language models and human cognitive processes. It can also aid research into the brains mechanisms of language processing within the context of the Chinese natural language.

neuroscience↗

bioRxiv2024

Neurotensin-Neurotensin Receptor 2 signaling in adipocytes regulates food intake through ceramide metabolism

Neurotensin (NTS) is a secretory peptide produced by the lymphatic endothelial cells (LEC). Our previous study revealed that NTS suppressed the activity of brown adipose tissue via the interactions with NTSR2. In the current study, we found that the depletion of Ntsr2 in the white adipocytes upregulated food intake, while the local treatment of NTS suppressed the food intake. Mechanistic study revealed that the suppression of NTS-NTSR2 signaling enhanced the phosphorylation of ceramide synthetase 2 (CerS2), increased the abundance of its products ceramide C20-C24 and downregulated the production of GDF15 in the white adipose tissues, which was responsible for the elevation of food intake. With four populations of different age and ethnic background, we discovered a potential causal and positive correlation between ceramide C20-24 and food intake in human. Our study identified that NTS-NTSR2 signaling can perform the neurological regulation via controlling the production of ceramide in the white adipocytes.

physiology↗