Dataset Information

Extracellular Vesicles from Adiponectin-Deficient Mice Mediate Skeletal Muscle Metabolic Dysfunction and Insulin Resistance

ABSTRACT: Adiponectin regulates systemic metabolism and enhances extracellular vesicle (EV) biogenesis, but the impact of adiponectin deficiency on circulating EV composition and their impact on muscle metabolism remains unclear. Here, we integrated proteomic analyses of plasma EVs from wild-type (WT) and adiponectin-knockout (KO) mice fed chow or high-fat diet (HFD) with metabolomic profiling of quadriceps from these mice and functional analyses in skeletal muscle cells treated with these EVs. Plasma EVs showed altered size distribution and distinct proteomic signatures: KO-HFD EVs were depleted of mitochondrial and glycolytic enzymes (CS, MDH2, ALDOA, TPI1) that were enriched in WT-HFD EVs. We observed that KO EVs blunted insulin-stimulated Akt phosphorylation, glucose uptake, and mitochondrial respiration in L6 myotubes, whereas WT-HFD EVs improved these responses. Proteomic profiling of recipient cells revealed compensatory up-regulation of metabolic and stress-response pathways overlapping with those diminished in KO EVs, suggesting adaptive remodeling of cellular metabolism. Furthermore, quadricep muscle metabolomics revealed genotype- and diet-specific reductions in amino acid-derived intermediates of the tricarboxylic-acid (TCA) and urea cycles, indicating altered catabolic flux in KO mice. These findings identify an adiponectin-EV axis coordinating muscle metabolic homeostasis, offering insight into inter-organ metabolic communication under dietary stress.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Skeletal Muscle Cell

SUBMITTER: Vincent Richard

LAB HEAD: Christoph H Borchers

PROVIDER: PXD070917 | Pride | 2026-08-03

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	EV006731_VR_SCPC059-09_Sweeney_EVs_DIA-PASEF_30SPD_S2_8127.d.zip	Other
	EV006732_VR_SCPC059-09_Sweeney_EVs_DIA-PASEF_30SPD_S6_8128.d.zip	Other
	EV006735_VR_SCPC059-09_Sweeney_EVs_DIA-PASEF_30SPD_S1_8131.d.zip	Other
	EV006741_VR_SCPC059-09_Sweeney_EVs_DIA-PASEF_30SPD_S5_8137.d.zip	Other
	EV006744_VR_SCPC059-09_Sweeney_EVs_DIA-PASEF_30SPD_S7_8140.d.zip	Other

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Publications

Extracellular vesicles: A dive into their role in the tumor microenvironment and cancer progression.

Lopez Kassandra K Lai Seigmund Wai Tsuen SWT Lopez Gonzalez Edwin De Jesus EJ Dávila Raúl G RG Shuck Sarah C SC

Frontiers in cell and developmental biology 20230321

Extracellular vesicles (EVs) encompass a diverse set of membrane-derived particles released from cells and are found in numerous biological matrices and the extracellular space. Specific classes of EVs include apoptotic bodies, exosomes, and microvesicles, which vary in their size, origin, membrane protein expression, and interior cargo. EVs provide a mechanism for shuttling cargo between cells, which can influence cell physiology by transporting proteins, DNA, and RNA. EVs are an abundant compo ...[more]

PMID: 37025182

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