title: Piromelatine decreases triglyceride accumulation in insulin resistant 3T3-L1 adipocytes: role of ATGL and HSL.
abstract: Piromelatine, a novel investigational multimodal sleep medicine, is developed for the treatment of patients with primary and co-morbid insomnia. Piromelatine has been shown to inhibit weight gain and improve insulin sensitivity in high-fat/high-sucrose-fed (HFHS) rats. Considering that piromelatine has also been implicated in lowering of triglyceride levels in HFHS rats, this work elucidated whether this effect involves in the regulation of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) in triglyceride (TG) metabolism. In this study, we investigated the effects of piromelatine and MT2 receptors inhibition on TG content, insulin-stimulated glucose uptake, and the expressions of ATGL and HSL in 3T3-L1 adipocytes preincubated in high glucose and high insulin (HGI) conditions. Our results showed that culturing 3T3-L1 adipocytes under HGI conditions increased triglyceride accumulation with concomitant decrease of ATGL and HSL expression, inducing insulin resistance in 3T3-L1 adipocytes. We also found that triglyceride accumulation was significantly inhibited and the levels of ATGL/HSL increased after melatonin or piromelatine treatment. The effects of melatonin/piromelatine (10 nM) were counteracted by pretreatment with the relatively selective MT2 receptor antagonist luzindole (100 nM). In this study, our data demonstrate that piromelatine reverses high glucose and high insulin-induced triglyceride accumulation in 3T3-L1 adipocytes, possibly through up-regulating of ATGL and HSL expression via a melatonin-dependent manner.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, China.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Wang
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: She
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: He
authors.forename: Wu-Jun
authors.initials: WJ
authors.lastname: Chen
authors.forename: Moshe
authors.initials: M
authors.lastname: Laudon
authors.forename: Xuan-Xuan
authors.initials: XX
authors.lastname: Xu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Yin
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects*; D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007333:Insulin Resistance; D008049:Lipase / Q000378:metabolism*; D051379:Mice; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D002787:Sterol Esterase / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D007211:Indoles; D008049:Lipase; D011714:Pyrans; D002787:Sterol Esterase; D014280:Triglycerides; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases; C581609:N-(2-(5-methoxy-indol-3-yl)-ethyl)-4-oxo-4H-pyran-2-carboxamide