Constitutive P2Y 2 receptor activity regulates basal lipolysis in human adipocytes

• Published in: Journal of cell science Vol. 131; no. 22
• Main Authors: Ali, Seema B, Turner, Jeremy J O, Fountain, Samuel J
• Format: Journal Article
• Language: English
• Published: England 19-11-2018
• Subjects: Adenosine Triphosphate - metabolism; Adenylyl Cyclases - metabolism; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; Adult; Aged; Calcium - metabolism; Cell Differentiation - drug effects; Cell Differentiation - physiology; Female; Humans; Lipolysis - drug effects; Middle Aged; Primary Cell Culture; Purinergic P2Y Receptor Antagonists - pharmacology; Receptors, Purinergic P2Y2 - metabolism; Signal Transduction; Calcium signalling; Human; Adipose tissue; Purinergic receptor
• EISSN: 1477-9137

White adipocytes are key regulators of metabolic homeostasis, which release stored energy as free fatty acids via lipolysis. Adipocytes possess both basal and stimulated lipolytic capacity, but limited information exists regarding the molecular mechanisms that regulate basal lipolysis. Here, we describe a mechanism whereby autocrine purinergic signalling and constitutive P2Y
receptor activation suppresses basal lipolysis in primary human
-differentiated adipocytes. We found that human adipocytes possess cytoplasmic Ca
tone due to ATP secretion and constitutive P2Y
receptor activation. Pharmacological antagonism or knockdown of P2Y
receptors increases intracellular cAMP levels and enhances basal lipolysis. P2Y
receptor antagonism works synergistically with phosphodiesterase inhibitors in elevating basal lipolysis, but is dependent upon adenylate cyclase activity. Mechanistically, we suggest that the increased Ca
tone exerts an anti-lipolytic effect by suppression of Ca
-sensitive adenylate cyclase isoforms. We also observed that acute enhancement of basal lipolysis following P2Y
receptor antagonism alters the profile of secreted adipokines leading to longer-term adaptive decreases in basal lipolysis. Our findings demonstrate that basal lipolysis and adipokine secretion are controlled by autocrine purinergic signalling in human adipocytes.