Related Experiment Video

Updated: Aug 5, 2026

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
09:41

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro

Published on: March 17, 2023

Adenosine Receptor 3 Antagonism Suppresses Adipogenesis via the EREG-EGFR-Leptin Axis in Multipotent Cells

Chia-Huei Lee1, Kuo-Yun Tseng2, Feng-Huei Lin3,4

  • 1National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.

Biofactors (Oxford, England)
|August 2, 2026
PubMed

Insights

Adenosine receptor 3 (AR3) antagonism inhibits fat cell differentiation by blocking the EREG-EGFR-leptin pathway. This discovery offers a new strategy for targeting adipose tissue in metabolic diseases.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolic Disease Research

Background:

  • The function of adenosine receptor 3 (AR3) in adipogenesis, the process of fat cell formation, is not well understood.
  • Understanding AR3's role is crucial for developing strategies to manage metabolic disorders characterized by altered adipose tissue.

Purpose of the Study:

  • To investigate the role of AR3 signaling in adipogenic differentiation.
  • To elucidate the molecular mechanisms underlying AR3's influence on fat cell formation.

Main Methods:

  • Utilized cell culture models (C3H10T1/2 and 3T3-L1) to study adipogenesis.
  • Employed AR3 antagonists (MRS1220) and agonists (CF101).
  • Performed transcriptomic profiling, gene expression analysis (PPARγ2, EREG, leptin), Western blotting for EGFR phosphorylation, and lipid accumulation assays.

Main Results:

  • AR3 antagonism with MRS1220 significantly inhibited adipogenic differentiation and reduced lipid accumulation.
  • MRS1220 induced epiregulin (EREG) expression, leading to EGFR activation and leptin upregulation, which mediated the anti-adipogenic effect.
  • AR3 knockdown abolished MRS1220's inhibitory effects, while AR3 agonism enhanced adipogenesis independently of the EREG-EGFR-leptin axis.

Conclusions:

  • Adenosine receptor 3 (AR3) is a key regulator of adipogenic differentiation.
  • An AR3-EREG-EGFR-leptin signaling cascade mediates the inhibitory effects of AR3 antagonism on adipogenesis.
  • Targeting AR3 presents a potential therapeutic strategy for modulating adipose tissue formation in metabolic diseases.
Keywords:
adenosine receptor 3adipogenesisepiregulinleptin

More Related Videos

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis08:34

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

Related Concept Videos

cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Adrenergic Receptors: β Subtype01:26

Adrenergic Receptors: β Subtype

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...
Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers01:22

Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers

α-Adrenergic antagonists, known as α-blockers, exert their effects by inhibiting α-adrenoceptors, leading to specific physiological actions. α1-blockers and α2-blockers have distinct pharmacological actions and therapeutic applications.
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally, α1-blockers effectively address urinary obstruction...
Adrenergic Receptors: ɑ Subtype01:31

Adrenergic Receptors: ɑ Subtype

Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Adrenergic Antagonists: Pharmacological Actions of β-Receptor Blockers01:27

Adrenergic Antagonists: Pharmacological Actions of β-Receptor Blockers

β-receptor blockers significantly impact the cardiovascular system by counteracting catecholamine-induced sympathetic responses. These medications decrease heart rate, contractility, and cardiac output, potentially leading to cardiac depression, life-threatening bradycardia, and death. Therapeutically, β-blockers function as mild antihypertensives and are utilized in treating angina pectoris and cardiac arrhythmias. However, nonselective β-blockers inhibit β2-receptors in bronchial smooth...