title: Lipolytic actions of secretin in mouse adipocytes.
abstract: Secretin (Sct), a classical gut hormone, is now known to play pleiotropic functions in the body including osmoregulation, digestion, and feeding control. As Sct has long been implicated to regulate metabolism, in this report, we have investigated a potential lipolytic action of Sct. In our preliminary studies, both Sct levels in circulation and Sct receptor (SctR) transcripts in adipose tissue were upregulated during fasting, suggesting a potential physiological relevance of Sct in regulating lipolysis. Using SctR knockout and Sct knockout mice as controls, we show that Sct is able to stimulate lipolysis in vitro in isolated adipocytes dose- and time-dependently, as well as acute lipolysis in vivo. H-89, a protein kinase A (PKA) inhibitor, was found to attenuate lipolytic effects of 1 μM Sct in vitro, while a significant increase in PKA activity upon Sct injection was observed in the adipose tissue in vivo. Sct was also found to stimulate phosphorylation at 660(ser) of hormone sensitive lipase (HSL) and to bring about the translocation of HSL from cytosol to the lipid droplet. In summary, our data demonstrate for the first time the in vivo and in vitro lipolytic effects of Sct, and that this function is mediated by PKA and HSL.
authors.affiliation: School of Biological Sciences, University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Revathi
authors.initials: R
authors.lastname: Sekar
authors.forename: Billy K C
authors.initials: BK
authors.lastname: Chow
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004822:Epididymis; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D008066:Lipolysis; D008297:Male; D051379:Mice; D010766:Phosphorylation; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics; D011964:Receptors, Gastrointestinal Hormone / Q000172:deficiency / Q000235:genetics; D012633:Secretin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013217:Starvation / Q000378:metabolism / Q000473:pathology; D002787:Sterol Esterase / Q000737:chemistry / Q000378:metabolism
chemical_list: D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D012633:Secretin; D017868:Cyclic AMP-Dependent Protein Kinases; D002787:Sterol Esterase
keywords: hormone sensitive lipase; lipolysis; protein kinase A; secretin receptor