PXD075390-2

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_2026-05-18_01:50:34.271.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
⏵ 2	2026-05-18 01:50:35	announced	2026-05-18: Add info.

Jiang H, Ni S, Li Z, Chen S, Li X, Zhang H, Shen WL, Jiang X, Luo P, Shu Y, Yuan F, Tong K, Xiao F, Guo F, HMGylation and RNA-binding function in male mice. Nat Commun, 17(1):(2026) [pubmed]

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