Dr. XuchaoLyu (Lv) reveived his bachelor's degree in biology and chemistry from Jilin University, China in 2011. He completed his Ph.D. in metabolism disease at Tsinghua University in 2019. He worked with Peng Li to study the mechanism of lipid droplet growth. He uncovered the unique lipid-permeable condensate that allows lipid transfer which is formed through 2D phase separation on the phospholipid membrane. Xuchao is currently a postdoc in Jonathan Long's lab at Stanford University. He is studying the secreted factors from various tissues during exercise. Outside of the lab, he enjoys eating and cooking.
Bachelor of Science, Jilin University (2011)
Doctor of Philosophy, Tsinghua University (2019)
PhD, Tsinghua Univeristy, Obesity and metabolism (2019)
BA, Jilin University, Biology and chemistiry (2011)
Jonathan Long, Postdoctoral Faculty Sponsor
An exercise-inducible metabolite that suppresses feeding and obesity.
Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases1-5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanine occurs in CNDP2+ cells, including macrophages, monocytes and other immune and epithelial cells localized to diverse organs. In diet-induced obese mice, pharmacological-mediated increases in Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases food intake and obesity following exercise training. Last, large activity-inducible increases in circulating Lac-Phe are also observed in humans and racehorses, establishing this metabolite as a molecular effector associated with physical activity across multiple activity modalities and mammalian species. These data define a conserved exercise-inducible metabolite that controls food intake and influences systemic energy balance.
View details for DOI 10.1038/s41586-022-04828-5
View details for PubMedID 35705806
Protocol for cell type-specific labeling, enrichment, and proteomic profiling of plasma proteins in mice.
1800; 2 (4): 101014
Secreted polypeptides represent a fundamental axis of intercellular communication. Here, we present a protocol for the cell type-specific biotinylation, enrichment, and proteomic profiling of secreted plasma proteins directly in mice. This protocol uses conditional "turn-on" adeno-associated viruses expressing an endoplasmic reticulum-targeted biotin ligase to globally biotinylate proteins of the secretory pathway in a cell type-specific manner. Biotinylated secreted proteins can be directly purified from blood plasma and analyzed by SDS-PAGE gel or shotgun proteomics. For complete information on the generation and use of this protocol, please refer to Wei et al. (2021).
View details for DOI 10.1016/j.xpro.2021.101014
View details for PubMedID 34950890
A gel-like condensation of Cidec generates lipid-permeable plates for lipid droplet fusion.
Membrane contact between intracellular organelles is important in mediating organelle communication. However, the assembly of molecular machinery at membrane contact site and its internal organization correlating with its functional activity remain unclear. Here, we demonstrate that a gel-like condensation of Cidec, a crucial protein for obesity development by facilitating lipid droplet (LD) fusion, occurs at the LD-LD contact site (LDCS) through phase separation. The homomeric interaction between the multivalent N terminus of Cidec is sufficient to promote its phase separation both in vivo and in vitro. Interestingly, Cidec condensation at LDCSs generates highly plastic and lipid-permeable fusion plates that are geometrically constrained by donor LDs. In addition, Cidec condensates are distributed unevenly in the fusion plate generating stochastic sub-compartments that may represent unique lipid passageways during LD fusion. We have thus uncovered the organization and functional significance of geometry-constrained Cidec phase separation in mediating LD fusion and lipid homeostasis.
View details for DOI 10.1016/j.devcel.2021.08.015
View details for PubMedID 34508658
Identification of gene products that control lipid droplet size in yeast using a high-throughput quantitative image analysis
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
2019; 1864 (2): 113-127
Lipid droplets (LDs) are important organelles involved in energy storage and expenditure. LD dynamics has been investigated using genome-wide image screening methods in yeast and other model organisms. For most studies, genes were identified using two-dimensional images with LD enlargement as readout. Due to imaging limitation, reduction of LD size is seldom explored. Here, we aim to set up a screen that specifically utilizes reduced LD size as the readout. To achieve this, a novel yeast screen is set up to quantitatively and systematically identify genes that regulate LD size through a three-dimensional imaging-based approach. Cidea which promotes LD fusion and growth in mammalian cells was overexpressed in a yeast knockout library to induce large LD formation. Next, an automated, high-throughput image analysis method that monitors LD size was utilized. With this screen, we identified twelve genes that reduced LD size when deleted. The effects of eight of these genes on LD size were further validated in fld1 null strain background. In addition, six genes were previously identified as LD-regulating genes. To conclude, this methodology represents a promising strategy to screen for players in LD size control in both yeast and mammalian cells to aid in the investigation of LD-associated metabolic diseases.
View details for DOI 10.1016/j.bbalip.2018.11.001
View details for Web of Science ID 000456224700001
View details for PubMedID 30414449