Ginseng extract inhibits lipolysis in rat adipocytes in vitro by activating phosphodiesterase 4.
Elevated concentrations of plasma free fatty acids (FFA) may cause insulin resistance. Inhibition of lipolysis reduces FFA availability and improves insulin sensitivity. Ginseng extract (Panax spp., GE) was shown to improve glycemia in Type 2 diabetes. In the present study, the antilipolytic effect of GE in rat adipocytes and the signaling pathway for GE antilipolysis were investigated. Adipocytes were isolated from rat fat tissue by collagenase digestion. The ability of GE to inhibit lipolysis was assessed by measuring glycerol and FFA release into the incubation medium. Phosphatidylinositol 3-kinase (PI3-K) inhibitor and various phosphodiesterase (PDE) inhibitors were applied to investigate the signaling pathway for GE antilipolysis. The present study showed that insulin and GE inhibited lipolysis by 42.4 and 49% compared with basal, respectively (P < 0.05). Unlike insulin, the PI3-K inhibitor wortmannin did not reverse GE antilipolysis, and GE did not affect phosphorylation of protein kinase B (PKB). The nonselective PDE inhibitor enprofylline reversed both insulin and GE antilipolysis. The specific phosphodiesterase 3 (PDE3) inhibitor cilostamide reversed insulin antilipolysis completely, but did not significantly affect GE antilipolysis. The specific phosphodiesterase 4 (PDE4) inhibitor rolipram did not significantly affect insulin antilipolysis, but almost completely reversed GE antilipolysis. Moreover, the combination of PDE3 and PDE4 inhibitors completely reversed GE antilipolysis. None of the ginsenosides (Rb1, Re, Rg1, Rc, Rb2, and Rd) were responsible for GE antilipolysis. The results suggest that ginseng exerts its antilipolytic effect through a signaling pathway different from that of insulin. GE antilipolysis is mediated in part by activating PDE4 in rat adipocytes.
Wang
Hong
H
The Ohio State University, Columbus, OH 43210, USA.
Reaves
Lisa A
LA
Edens
Neilé K
NK
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004789:Enzyme Activation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D005894:Panax / Q000737:chemistry*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010936:Plant Extracts; D015363:Quinolones; C021294:cilostamide; D051057:Proto-Oncogene Proteins c-akt; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005990:Glycerol