PXD039910-1

PXD039910 is an original dataset announced via ProteomeXchange.

Title	Hepatic Glucuronyl C5-epimerase combats obesity via stabilizing GDF15
Description	Background & Aims: Disturbed hepatic metabolism frequently results in excessive lipid accumulation in adipose. The causal mechanism underlying the interplay of the liver-adipose axis on how to maintain lipid homeostasis is not fully elucidated. This study investigated the role of hepatic Glucuronyl C5-epimerase (Glce) in obesity. Methods: We investigated the expression of Glce in liver of obese patients which were divided according to their body mass index (BMI). Obesity models were established in hepatic Glce-knockout and wild-type mice fed a high-fat diet (HFD) for 16 weeks. The role of Glce protein in the progression of disrupted hepatokine secretion was examined using a secretome analysis. Results: Hepatic Glce expression was inversely related to the BMI values of obese patients. Decreased Glce was also detected in an HFD murine model. Hepatic Glce deficiency led to impaired thermogenesis in adipose tissue and exacerbated diet-induced obesity. Intriguingly, reduced circulating growth differentiation factor 15 (GDF15) was observed in Glce-knockout mice. Treatment with recombinant GDF15 obstructed fat accumulation in the absence of Glce, an effect that was similar to the re-expression of Glce and its active site mutants both in vitro and in vivo. Furthermore, Glce deletion not only reduced GDF15 mature form but also disrupted the ubiquitination of GDF15 probably due to their interaction. Conclusions: Hepatic Glce deletion facilitates the obesity independent of its enzyme activity. Decreased Glce reduced the secretion of GDF15 which perturbed lipid homeostasis in vivo, highlighting the role of a novel Glce-GDF15 axis in energy balance which might be a potential target for combating obesity.
HostingRepository	iProX
AnnounceDate	2023-02-07
AnnouncementXML	Submission_2023-02-06_20:33:42.116.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hongwen Zhu
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-06 20:33:19	ID requested
⏵ 1	2023-02-06 20:33:42	announced

Dataset with its publication pending

submitter keyword: glucuronyl C5-epimerase, growth differentiation factor-15, obesity, energy expenditure, ubiquitination

Hu Zhou
contact affiliation	Shanghai Institute of Materia Medica
contact email	zhouhu@simm.ac.cn
lab head
Hongwen Zhu
contact affiliation	Shanghai Institute of Materia Medica
contact email	zhw@simm.ac.cn
dataset submitter

iProX dataset URI