ArticleMolecular metabolism2018
Phosphorylation of Beta-3 adrenergic receptor at serine 247 by ERK MAP kinase drives lipolysis in obese adipocytes.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
- Pharmacological protection from a sugar-rich diet through inhibition of Ras/MAPK signaling.iScience · 2026Article
- DUSP4 activates adipocyte thermogenesis via CRTC3 dephosphorylation-dependent UCP1 expression.Experimental & molecular medicine · 2026Article
- β3-AR/β-arrestin2 Interaction Triggers Cardiac Fibrosis Through JNK/c-Jun Pathway in Cardiac Fibroblasts.Journal of cellular and molecular medicine · 2026Article
- Comparative analysis of naked mole-rat thermogenesis and its potential to maintain euthermia in response to cold.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Inhibition of adipocyte lipolysis by vaspin impairs thermoregulation in vivo.Nature communications · 2025Article
- The suprachiasmatic nucleus regulates brown fat thermogenesis in male mice through an adrenergic receptor ADRB3-S100B signaling pathway.PLoS biology · 2025Article
- Depot-specific roles for sphingosine kinase 1 in conversion of white adipose to thermogenic adipose.bioRxiv : the preprint server for biology · 2025Article
- Vitamin D receptor signalling regulates the diet-driven metabolic shift during weaning.Molecular metabolism · 2025Article
- Temporal Relationship Between Visceral Fat and Inflammation, and Their Joint Effect on Cardiometabolic Diseases: Evidence from the China Health and Retirement Longitudinal Study (CHARLS).Journal of inflammation research · 2025Article
- Endotoxin-induced alterations of adipose tissue function: a pathway to bovine metabolic stress.Journal of animal science and biotechnology · 2024Review
- The Complex Interplay of Insulin Resistance and Metabolic Inflammation in Transition Dairy Cows.Animals : an open access journal from MDPI · 2024Review
- Excessive or sustained endoplasmic reticulum stress: one of the culprits of adipocyte dysfunction in obesity.Therapeutic advances in endocrinology and metabolism · 2024Review
- Germinated Rice Seeds Improved Resveratrol Production to Suppress Adipogenic and Inflammatory Molecules in 3T3-L1 Adipocytes.Molecules (Basel, Switzerland) · 2023Article
- Differential remodeling of subcutaneous white and interscapular brown adipose tissue by long-term exercise training in aged obese female mice.Journal of physiology and biochemistry · 2023Article
- Wds-Mediated H3K4me3 Modification Regulates Lipid Synthesis and Transport inInternational journal of molecular sciences · 2023Article
- Obese visceral fat tissue inflammation: from protective to detrimental?BMC medicine · 2022Review
- [Serum free fatty acid level in children with primary hypertension].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2022Article
- Oncostatin M Induces Lipolysis and Suppresses Insulin Response in 3T3-L1 Adipocytes.International journal of molecular sciences · 2022Article
- Phillyrin restores metabolic disorders in mice fed with high-fat diet through inhibition of interleukin-6-mediated basal lipolysis.Frontiers in nutrition · 2022Article
- Loss of Adipocyte STAT5 Confers Increased Depot-Specific Adiposity in Male and Female Mice That Is Not Associated With Altered Adipose Tissue Lipolysis.Frontiers in endocrinology · 2022Article
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveThe inappropriate release of free fatty acids from obese adipose tissue stores has detrimental effects on metabolism, but key molecular mechanisms controlling FFA release from adipocytes remain undefined. Although obesity promotes systemic inflammation, we find activation of the inflammation-associated Mitogen Activated Protein kinase ERK occurs specifically in adipose tissues of obese mice, and provide evidence that adipocyte ERK activation may explain exaggerated adipose tissue lipolysis observed in obesity. METHODS AND
resultsWe provide genetic and pharmacological evidence that inhibition of the MEK/ERK pathway in human adipose tissue, mice, and flies all effectively limit adipocyte lipolysis. In complementary findings, we show that genetic and obesity-mediated activation of ERK enhances lipolysis, whereas adipose tissue specific knock-out of ERK2, the exclusive ERK1/2 protein in adipocytes, dramatically impairs lipolysis in explanted mouse adipose tissue. In addition, acute inhibition of MEK/ERK signaling also decreases lipolysis in adipose tissue and improves insulin sensitivity in obese mice. Mice with decreased rates of adipose tissue lipolysis in vivo caused by either MEK or ATGL pharmacological inhibition were unable to liberate sufficient White Adipose Tissue (WAT) energy stores to fuel thermogenesis from brown fat during a cold temperature challenge. To identify a molecular mechanism controlling these actions, we performed unbiased phosphoproteomic analysis of obese adipose tissue at different time points following acute pharmacological MEK/ERK inhibition. MEK/ERK inhibition decreased levels of adrenergic signaling and caused de-phosphorylation of the β3-adrenergic receptor (β3AR) on serine 247. To define the functional implications of this phosphorylation, we showed that CRISPR/Cas9 engineered cells expressing wild type β3AR exhibited β3AR phosphorylation by ERK2 and enhanced lipolysis, but this was not seen when serine 247 of β3AR was mutated to alanine.
conclusionTaken together, these data suggest that ERK activation in adipocytes and subsequent phosphorylation of the β3AR on S247 are critical regulatory steps in the enhanced adipocyte lipolysis of obesity.
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