Key role of heat shock protein 90 in leptin-induced STAT3 activation and feeding regulation.

BACKGROUND AND PURPOSE: Leptin, an important regulator of the energy balance, acts on the brain to inhibit feeding. However, the mechanisms involved in leptin signalling have not yet been fully elucidated. Heat shock protein 90 (HSP90) is a molecular chaperone that is involved in regulating cellular homeostasis. In the present study, we investigated the possible involvement of HSP90 in leptin signal transduction. EXPERIMENTAL APPROACH: HEK293 and SH-SY5Y cell lines stably transfected with the Ob-Rb leptin receptor (HEK293 Ob-Rb, SH-SY5Y Ob-Rb) were used in the present study. Phosphorylation of JAK2 and STAT3 was analysed by western blotting. An HSP90 inhibitor was administered i.c.v. into rats and their food intake was analysed. KEY RESULTS: The knock-down of HSP90 in the HEK293 Ob-Rb cell line attenuated leptin-induced JAK2 and STAT3 signalling. Moreover, leptin-induced JAK2/STAT3 phosphorylation was markedly attenuated by the HSP90 inhibitors geldanamycin, radicicol and novobiocin. However, these effects were not mediated through previously known factors, which are known to be involved in the development of leptin resistance, such as suppressor of cytokine signalling 3 or endoplasmic reticulum stress. The infusion of an HSP90 inhibitor into the CNS blunted the anorexigenic actions of leptin in rats (male Wister rat). CONCLUSIONS AND IMPLICATIONS: HSP90 may be a novel factor involved in leptin-mediated signalling that is linked to anorexia.

Possible involvement of 15-deoxy-Δ(12,14) -prostaglandin J2 in the development of leptin resistance.

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.

Estimation of direction of attention using EEG and out-of-head sound localization.

Brain-Machine Interfaces (BMIs) are being researched controlling external devices such as robots and computers by measuring the cranial nerve activity of the operator. The brain activities evoked by visual stimuli have been studied intensively. However, few studies have considered a BMI that uses the brain activities evoked by auditory stimuli. This study investigated whether a person's direction of attention can be estimated using an event-related potential (ERP) generated by selective attention to an auditory stimulus. An auditory stimulus and an out-of-head sound localization system that can create an audio image outside the head that is presented through an earphone were used instead of a loudspeaker system. This system was experimentally evaluated by presenting the subject auditory cues from one of six directions while the subject directed his attention in one direction. An EEG response similar to an ERP was observed. The direction of attention was estimated using support vector machine with an accuracy of 89.2[%] on average for the three subjects. This suggests that a BMI system based on the estimated direction of attention can be developed by using out-of-head sound localization.