title: Possible involvement of 15-deoxy-Δ(12,14) -prostaglandin J2 in the development of leptin resistance.
abstract: Obesity is a worldwide health problem that urgently needs to be solved. Leptin is an anti-obesity hormone that activates satiety signals to the brain. Evidence to suggest that leptin resistance is involved in the development of obesity is increasing; however, the molecular mechanisms involved remain unclear. We herein demonstrated that 15-deoxy-Δ(12,14) -prostaglandin J2 (15d-PGJ2 ) was involved in the development of leptin resistance. A treatment with 15d-PGJ2 inhibited the leptin-induced activation of signal transducer and activator of transcription 3 (STAT3) in neuronal cells (SH-SY5Y-Ob-Rb cells). Furthermore, the intracerebroventricular administration of 15d-PGJ2 reversed the inhibitory effects of leptin on food intake in rats. The peroxisome proliferator-activated receptor gamma (PPAR-γ) antagonist, GW9662, slightly reversed the inhibitory effects of 15d-PGJ2 on the leptin-induced activation of STAT3 in neuronal cells. The PPAR-γ agonist, rosiglitazone, also inhibited leptin-induced STAT3 phosphorylation. Therefore, the inhibitory effects of 15d-PGJ2 may be mediated through PPAR-γ. On the other hand, 15d-PGJ2 -induced leptin resistance may not be mediated by endoplasmic reticulum stress or suppressor of cytokine signaling 3. The results of the present study suggest that 15d-PGJ2 is a novel factor for the development of leptin resistance in obesity. Leptin resistance, an insensitivity to the actions of leptin, is involved in the development of obesity. Here, we found 15-deoxy-Δ(12,14) -prostaglandin J2 (15d-PGJ2 ) may be involved in the development of leptin resistance. The present results suggest that the 15d-PGJ2 may be a novel factor for the development of leptin resistance in obesity. 15d-PGJ2 , 15-Deoxy-Δ(12,14) -prostaglandin J2; STAT3, signal tranducer and activator of transcription 3.
authors: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors: Toru
authors: T
authors: Hosoi
authors: Syu
authors: S
authors: Matsuzaki
authors: Tsuyoshi
authors: T
authors: Miyahara
authors: Kaori
authors: K
authors: Shimizu
authors: Yuki
authors: Y
authors: Hasegawa
authors: Koichiro
authors: K
authors: Ozawa
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004435:Eating / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007276:Injections, Intraventricular; D020738:Leptin / Q000008:administration & dosage*; D008297:Male; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D054411:Receptors, Leptin / Q000819:agonists / Q000378:metabolism
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D020738:Leptin; D054411:Receptors, Leptin; D015230:Prostaglandin D2
keywords: 15d-PGJ2; PPAR-γ; STAT3; leptin