Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/474288

IL-25 induces beige fat to improve metabolic homeostasis via macrophage and innervation

Li, L.·Ma, L.·Feng, J.·Gong, B.·Li, J.·Hu, T.·Zhao, Z.·Qi, W.·Zhou, T.·Yang, X.·Gao, G.·Yang, Z.
View original source ↗Export metadata ↓

Abstract

Beige fat dissipates energy and functions as a defense against cold and obesity, but the underlying mechanisms remain unclear. We found that the signaling of interleukin (IL)-25 including its cognate receptor, IL-17 receptor B (IL-17RB), increased in adipose tissue upon cold and {beta}3-adrenoceptor agonist stimulation. IL-25 induced the browning effect in white adipose tissue (WAT) by releasing IL-4, 13 and promoting alternative activation of macrophages to regulate innervation, which characterized as tyrosine hydroxylase (TH) up-regulation to produce more catecholamine including norepinephrine. Blockade of IL-4R and depletion of macrophages with clodronate-loaded liposomes in vivo significantly impaired the browning of WAT. Obese mice administered with IL-25 were protected from obesity on a high-fat diet and the subsequent metabolic disorders, and the process involved the uncoupling protein 1 (UCP1)-mediated thermogenesis. In conclusion, the activation of IL-25 signaling on beige fat might play a therapeutic potential for obesity and its associated metabolic disorders.

Explore related subjects

biochemistryPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Li, L., Ma, L., Feng, J., Gong, B., Li, J., Hu, T., Zhao, Z., Qi, W., Zhou, T., Yang, X., Gao, G., Yang, Z.. 2018-11-19. IL-25 induces beige fat to improve metabolic homeostasis via macrophage and innervation. https://doi.org/10.1101/474288

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Structural basis for inefficient G protein coupling by Frizzled receptors

Frizzleds (FZDs) are class F G protein-coupled receptors (GPCRs) that primarily signal through Dishevelled (DVL) to initiate Wnt signalling, with evidence for context-specific coupling to heterotrimeric G proteins. Every FZD-G protein structure to date has been determined without an agonist, implying that agonist binding is not required for stable complex formation in vitro and directly contradicting the difficulty of demonstrating G protein coupling in cells. All these structures contain unassigned density between the receptor and the heterotrimeric G protein. From structures generated by single-particle cryo-electron microscopy (cryo-EM) of FZD7-Gs and FZD5-Gq, we identify this density as the detergent lauryl maltose neopentyl glycol (LMNG), which bridges the receptor and G protein to stabilise a weak, shallow interface. Absence of LMNG - in biochemical preparations and molecular dynamics simulations - destabilises the complex, showing that constitutive FZD-G protein engagement is intrinsically weak. The weak G protein coupling is governed by a conserved intracellular interface that when mutated differentially influences DVL and G protein signalling. Our findings show that LMNG has masked the instability of purified FZD-G protein complexes and provide the structural basis of FZDs as inherently weak G protein activators that are predisposed to DVL signalling.

biochemistry↗
bioRxiv2026

A Binuclear Cluster Supports Functional Asymmetry in Dark-Operative Protochlorophyllide Reductase

Many photosynthetic bacteria rely on the nitrogenase-like dark-operative protochlorophyllide oxidoreductase (DPOR) to sustain (bacterio)chlorophyll synthesis in the dark. DPOR couples ATP hydrolysis to electron transfer from a reducing component (L-protein) to a catalytic component (NB-protein) that reduces protochlorophyllide. NB-protein is an 2{beta}2 heterotetramer, and each heterodimeric half contains an active site and a [Fe4S4] cluster. Although the two halves are identical, they react sequentially rather than in parallel. How the two halves communicate has remained unknown. Here we show, using Cu K-edge x-ray absorption spectroscopy and cryo-EM, that the NB-protein tetramer interface holds a binuclear, sulfur-bridged [Cu2S2] cluster. Each Cu is reduced and three-coordinate, with short Cu-S and Cu-Cu distances (2.26 and 2.62 &Aring). Mutagenesis excludes the nearest cysteine as the bridging ligand, supporting inorganic sulfide as the most likely sulfur donor. To our knowledge, this is the first sulfide-bridged dicopper cluster identified in a protein. The cluster is conserved in three purple non-sulfur bacteria and connects the BchB C-terminal helices that contact opposing active sites. Loss of Cu abolishes DPOR activity and asymmetric L-protein binding without disturbing overall fold. We propose that the cluster relays substrate-binding information between active sites, suggesting a metal-mediated mechanism for cooperativity in nitrogenase-like enzymes.

biochemistry↗
bioRxiv2026

Jade1S SUMOylates tau and targets oligomers for degradation

The accumulation of insoluble tau aggregates is a pathological hallmark of tauopathies, including Alzheimer's disease. While molecular chaperones and clearance pathways regulate tau homeostasis, the mechanisms governing tau oligomerization and degradation remain incompletely defined. Recent genome-wide association studies (GWAS) have linked the JADE1 locus to tauopathy, and the PHD zinc finger protein Jade1S has been identified in complexes with tau in post-mortem brain tissue, prompting investigation into their biochemical relationship. Here, we characterize the reciprocal interactions between Jade1S and 0N4R tau stability and turnover. Covalent labeling mass spectrometry and co-immunoprecipitation mappings reveal that Jade1S binds wild-type 0N4R tau through redundant sites within its N-terminal and plant homeodomain (PHD) zinc finger domains. In vitro assays demonstrate that Jade1S functions as a SUMO E3 ligase, utilizing its PHD domains to mediate tau SUMOylation. Cell-based cycloheximide chase assays reveal a reciprocal stabilization dynamic: tau co-expression extends the overall physiological half-life of Jade1S from less than an hour to ~17 hours, arresting its turnover specifically within sarkosyl-insoluble fractions. Conversely, Jade1S selectively accelerates the degradation of sarkosyl-insoluble tau without altering the turnover of the soluble monomeric pool over chased time. Mechanistically, Jade1S redirects the clearance of SUMO2/3-modified tau oligomers away from basal autophagic-lysosomal pathways and toward proteasome-dependent degradation. Furthermore, Jade1S exhibits intrinsic molecular chaperone activity, inhibiting arachidonic acid-induced tau oligomerization in vitro. Together, these data characterize Jade1S as a dual-function SUMO ligase and chaperone that regulates tau stability, prevents oligomer assembly, and promotes the targeted proteasomal clearance of aggregated tau.

biochemistry↗