Browsing by Author "Guo, Xiao"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Neurotensin-neurotensin receptor 2 signaling in adipocytes suppresses food intake through regulating ceramide metabolism
    (Springer Nature, 2025) Fu, Wei; Lai, Yuanting; Li, Kexin; Yang, Yue; Guo, Xiao; Gong, Qifan; Zhou, Xiaofeng; Zhou, Liying; Liu, Cenxi; Zhang, Zhi; So, Jisun; Zhang, Yufeng; Huang, Lin; Lu, Guangxing; Yi, Chuanyou; Wang, Qichu; Fan, Chenyu; Liu, Chao; Wang, Jiaxing; Yu, Haiyi; Zhao, Yimin; Huang, Tao; Roh, Hyun Cheol; Liu, Tiemin; Tang, Huiru; Qi, Jianping; Xu, Ming; Zheng, Yan; Huang, He; Li, Jin; Biochemistry and Molecular Biology, School of Medicine
    Neurotensin (NTS) is a secretory peptide produced by lymphatic endothelial cells. Our previous study revealed that NTS suppressed the activity of brown adipose tissue via interactions with NTSR2. In the current study, we found that the depletion of Ntsr2 in white adipocytes upregulated food intake, while the local treatment of NTS suppressed food intake. Our mechanistic study revealed that suppression of NTS-NTSR2 signaling enhanced the phosphorylation of ceramide synthetase 2, increased the abundance of its products ceramides C20-C24, and downregulated the production of GDF15 in white adipose tissues, which was responsible for the elevation of food intake. We discovered a potential causal and positive correlation between serum C20-C24 ceramide levels and human food intake in four populations with different ages and ethnic backgrounds. Together, our study shows that NTS-NTSR2 signaling in white adipocytes can regulate food intake via its direct control of lipid metabolism and production of GDF15. The ceramides C20-C24 are key factors regulating food intake in mammals.
  • Thumbnail Image
    Item
    The roles of SMYD4 in epigenetic regulation of cardiac development in zebrafish
    (PLOS, 2018-08-15) Xiao, Deyong; Wang, Huijun; Hao, Lili; Guo, Xiao; Ma, Xiaojing; Qian, Yanyan; Chen, Hongbo; Ma, Jing; Zhang, Jin; Sheng, Wei; Shou, Weinian; Huang, Guoying; Ma, Duan; Pediatrics, School of Medicine
    SMYD4 belongs to a family of lysine methyltransferases. We analyzed the role of smyd4 in zebrafish development by generating a smyd4 mutant zebrafish line (smyd4L544Efs*1) using the CRISPR/Cas9 technology. The maternal and zygotic smyd4L544Efs*1 mutants demonstrated severe cardiac malformations, including defects in left-right patterning and looping and hypoplastic ventricles, suggesting that smyd4 was critical for heart development. Importantly, we identified two rare SMYD4 genetic variants in a 208-patient cohort with congenital heart defects. Both biochemical and functional analyses indicated that SMYD4(G345D) was pathogenic. Our data suggested that smyd4 functions as a histone methyltransferase and, by interacting with HDAC1, also serves as a potential modulator for histone acetylation. Transcriptome and bioinformatics analyses of smyd4L544Efs*1 and wild-type developing hearts suggested that smyd4 is a key epigenetic regulator involved in regulating endoplasmic reticulum-mediated protein processing and several important metabolic pathways in developing zebrafish hearts.