PXD068547

PXD068547 is an original dataset announced via ProteomeXchange.

Title	Adipose GGPPS Stabilizes BCAT2 to Orchestrate BCAA Catabolism and Lipid Mobilization in Fasting-Induced Liver Remodeling
Description	Organisms adapt to fasting by remodeling energy metabolism across tissues, with white adipose tissue (WAT) serving as a key energy reservoir. However, the molecular cues that initiate lipid mobilization during early fasting remain incompletely defined. Here, we identify geranylgeranyl pyrophosphate synthase (GGPPS) as a fasting-responsive regulator that orchestrates lipolysis and branched-chain amino acid (BCAA) metabolism. In mice, 24 hours of fasting marks a metabolic inflection point characterized by hepatic triglyceride accumulation, WAT mass reduction, and a sharp elevation in circulating BCAAs. Proteomic profiling revealed that fasting downregulates GGPPS in both inguinal and epididymal WAT, which in turn destabilizes BCAT2-a key BCAA-catabolizing enzyme-via enhanced K63-linked ubiquitination. Mechanistically, GGPPS scaffolds the deubiquitinase OTUB1 and BCAT2 to stabilize BCAT2 protein level, thereby promoting BCAA catabolism. Elevated BCAAs activate lipolysis in adipocytes and enhance hepatic fatty acid oxidation. Adipose-specific deletion of Ggpps in mice phenocopies fasting responses, including enhanced lipolysis, hepatic lipid accumulation, and systemic BCAA elevation. Conversely, BCAA supplementation promotes adipose lipolysis, protects against diet-induced obesity, and facilitates hepatic oxidative adaptation. Importantly, we found that BCAA supplementation during fasting not only enhanced weight loss efficiency, but also prevented aberrant hepatic lipid accumulation typically induced by prolonged fasting in mice. These findings uncover GGPPS as a central node linking amino acid and lipid metabolism during early fasting and establish a multi-organ metabolic circuit that coordinates the transition from carbohydrate to lipid-based energy utilization.
HostingRepository	iProX
AnnounceDate	2025-09-18
AnnouncementXML	Submission_2026-07-26_18:15:57.563.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mingjie Zou
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	ZenoTOF 7600

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-19 02:25:21	ID requested
⏵ 1	2026-07-26 18:15:58	announced

Dataset with its publication pending

submitter keyword: Fasting, Geranylgeranyl pyrophosphate synthase (GGPPS), Branched-chain amino acid (BCAA) metabolism, Adipose lipolysis, branched-chain amino acid transaminase 2 (BCAT2)

Lei Fang
contact affiliation	Nanjing University
contact email	njfanglei@nju.edu.cn
lab head
Mingjie Zou
contact affiliation	Nanjing University
contact email	502023350059@smail.nju.edu.cn
dataset submitter

iProX dataset URI