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Possible involvement of 15‐deoxy‐Δ 12,14 ‐prostaglandin J 2 in the development of leptin resistance
Author(s) -
Hosoi Toru,
Matsuzaki Syu,
Miyahara Tsuyoshi,
Shimizu Kaori,
Hasegawa Yuki,
Ozawa Koichiro
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13057
Subject(s) - leptin , leptin receptor , endocrinology , medicine , receptor , prostaglandin , socs3 , hormone , chemistry , biology , signal transduction , obesity , microbiology and biotechnology , stat3
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 J 2 (15d‐ PGJ 2 ) was involved in the development of leptin resistance. A treatment with 15d‐ PGJ 2 inhibited the leptin‐induced activation of signal transducer and activator of transcription 3 ( STAT 3) in neuronal cells ( SH ‐ SY 5Y‐Ob‐Rb cells). Furthermore, the intracerebroventricular administration of 15d‐ PGJ 2 reversed the inhibitory effects of leptin on food intake in rats. The peroxisome proliferator‐activated receptor gamma ( PPAR ‐γ) antagonist, GW 9662, slightly reversed the inhibitory effects of 15d‐ PGJ 2 on the leptin‐induced activation of STAT 3 in neuronal cells. The PPAR ‐γ agonist, rosiglitazone, also inhibited leptin‐induced STAT 3 phosphorylation. Therefore, the inhibitory effects of 15d‐ PGJ 2 may be mediated through PPAR ‐γ. On the other hand, 15d‐ PGJ 2 ‐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‐ PGJ 2 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 J 2 (15d‐PGJ 2 ) may be involved in the development of leptin resistance. The present results suggest that the 15d‐PGJ 2 may be a novel factor for the development of leptin resistance in obesity. 15d‐PGJ 2 , 15‐Deoxy‐Δ 12,14 ‐prostaglandin J2; STAT3 , signal tranducer and activator of transcription 3.