PXD075390

PXD075390 is an original dataset announced via ProteomeXchange.

Title	Leucine catabolic enzyme AUH regulates brown fat thermogenesis through HMGylation of PPARγ and RNA-binding function in male mice
Description	A strong association between leucine and obesity has been well established; however, the role of leucine catabolic enzymes in adipose tissue remains largely unknown. Here, we show that knockdown of the leucine catabolic enzyme AU RNA binding methylglutaconyl-CoA hydratase (AUH) in brown adipocytes reduces thermogenesis, while AUH over-expression has the opposite effect both in vivo and in vitro. Mechanistically, AUH partially promotes uncoupling protein 1 (UCP1) expression through its metabolite 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA). HMG-CoA directly HMGylates peroxisome proliferator-activated receptor gamma (PPARγ) on lysine 386, enhancing its transcriptional activity to increase UCP1 expression. In addition, AUH binds to and stabilizes Ucp1 mRNA via its RNA-binding function. Moreover, we discover that AUH promotes white adipose tissue browning; AUH expression in human white adipose tissue is inversely correlated with adiposity, and over-expression of AUH in adipose tissue protects mice against high-fat diet-induced obesity. Collectively, these results provide new insights into the crosstalk between amino acid metabolism and thermogenesis and identify a novel post-translational modification of PPARγ.
HostingRepository	iProX
AnnounceDate	2026-03-09
AnnouncementXML	Submission_2026-03-09_01:57:36.275.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haizhou Jiang
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-09 01:57:21	ID requested
⏵ 1	2026-03-09 01:57:36	announced

Dataset with its publication pending

submitter keyword: Leucine, AUH, brown fat, thermogenesis, HMGylation, PPARγ, RNA-binding protein

Feifan Guo
contact affiliation	Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai Medical College, Fudan University
contact email	ffguo@fudan.edu.cn
lab head
Haizhou Jiang
contact affiliation	Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai Medical College, Fudan University
contact email	hzjiang@fudan.edu.cn
dataset submitter

iProX dataset URI