ArticleNature metabolism2024
p21-activated kinase 4 counteracts PKA-dependent lipolysis by phosphorylating FABP4 and HSL.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- p21-activated kinase 4 drives hepatic stellate cell activation and liver fibrosis through the phosphorylation of YAP at T428.Signal transduction and targeted therapy · 2026Article
- PAK4 in metabolic diseases: regulation by nutrient signals and therapeutic implications.Experimental & molecular medicine · 2026Review
- Cyanidin-3-O-galactoside improves meat quality, flavor and health attributes in small-tailed han lambs.NPJ science of food · 2026Article
- Sirt6 deficiency in mast cells promotes adipose fibroinflammation in obesity through galectin-3 signaling.Nature communications · 2026Article
- Association between HbA1c/HDL-C ratio and diabetic foot ulcer: a cross-sectional study based on the Han population in Northwest China.Frontiers in nutrition · 2026Article
- The nature of sex differences in catecholamine-induced lipolysis in subcutaneous fat cells.iScience · 2025Article
- Negative Impact of p21-Activated Kinase 4-Mediated AMP-Activated Protein Kinase Inhibition on Sarcopenia in Mice and Humans.MedComm · 2025Article
- PAK4 phosphorylates cyclin-dependent kinase 2 to promote the GExperimental & molecular medicine · 2025Article
- Ret finger protein deficiency attenuates adipogenesis in male mice with high fat diet-induced obesity.Experimental & molecular medicine · 2025Article
- Exercise-regulated lipolysis: Its role and mechanism in health and diseases.Journal of advanced research · 2025Review
- PAK4 promotes the cytoskeletal organization and meiotic maturation via phosphorylating DDX17 in oocyte.Cell communication and signaling : CCS · 2025Article
- Inhibitory effects of cashew Anacardium occidentale L. kernel, apple, and shell extracts on lipid accumulation and adipogenesis in 3T3-L1 adipocytes.Scientific reports · 2025Article
- Transcriptional regulation of adipocyte lipolysis by IRF2BP2.Science advances · 2025Article
- Article
- Association between the atherogenic index of plasma, body mass index, and cardiovascular diseases in Chinese middle and old-aged adults: a mediation analysis.Frontiers in cardiovascular medicine · 2025Article
- PAK4 phosphorylates and inhibits AMPKα to control glucose uptake.Nature communications · 2024Article
- Avellanin A Has an Antiproliferative Effect on TP-Induced RWPE-1 Cells via the PI3K-Akt Signalling Pathway.Marine drugs · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adipose tissue lipolysis is mediated by cAMP-protein kinase A (PKA)-dependent intracellular signalling. Here, we show that PKA targets p21-activated kinase 4 (PAK4), leading to its protein degradation. Adipose tissue-specific overexpression of PAK4 in mice attenuates lipolysis and exacerbates diet-induced obesity. Conversely, adipose tissue-specific knockout of Pak4 or the administration of a PAK4 inhibitor in mice ameliorates diet-induced obesity and insulin resistance while enhancing lipolysis. Pak4 knockout also increases energy expenditure and adipose tissue browning activity. Mechanistically, PAK4 directly phosphorylates fatty acid-binding protein 4 (FABP4) at T126 and hormone-sensitive lipase (HSL) at S565, impairing their interaction and thereby inhibiting lipolysis. Levels of PAK4 and the phosphorylation of FABP4-T126 and HSL-S565 are enhanced in the visceral fat of individuals with obesity compared to their lean counterparts. In summary, we have uncovered an important role for FABP4 phosphorylation in regulating adipose tissue lipolysis, and PAK4 inhibition may offer a therapeutic strategy for the treatment of obesity.
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