Rimonabant has been shown to not only decrease the food intake and body weight but also to increase serum adiponectin levels. This increase of the serum adiponectin levels has been hypothesized to be related to the rimonabant-induced amelioration of insulin resistance linked to obesity, although experimental evidence to support this hypothesis is lacking. To test this hypothesis experimentally, we generated adiponectin knock-out (adipo(؊/؊))ob/ob mice. After 21 days of 30 mg/kg rimonabant, the body weight and food intake decreased to similar degrees in the ob/ob and adipo(؊/؊)-ob/ob mice. Significant improvement of insulin resistance was observed in the ob/ob mice following rimonabant treatment, associated with significant up-regulation of the plasma adiponectin levels, in particular, of high molecular weight adiponectin. Amelioration of insulin resistance in the ob/ob mice was attributed to the decrease of glucose production and activation of AMP-activated protein kinase (AMPK) in the liver induced by rimonabant but not to increased glucose uptake by the skeletal muscle. Interestingly, the rimonabanttreated adipo(؊/؊)ob/ob mice also exhibited significant amelioration of insulin resistance, although the degree of improvement was significantly lower as compared with that in the ob/ob mice. The effects of rimonabant on the liver metabolism, namely decrease of glucose production and activation of AMPK, were also less pronounced in the adipo(؊/؊)-ob/ob mice. Thus, it was concluded that rimonabant ameliorates insulin resistance via both adiponectin-dependent and adiponectin-independent pathways.The prevalence of obesity has increased dramatically in recent years (1, 2). It is commonly associated with type 2 diabetes, coronary artery disease, and hypertension, and the coexistence of these diseases in subjects has been termed the metabolic syndrome (3). There is a demand for effective and safe antiobesity agents that can produce and maintain weight loss and improve the metabolic syndrome.The newly discovered endocannabinoid system, consisting of the CB-1 (cannabinoid type-1) receptor and endogenous lipid-derived ligands, contributes to the physiological regulation of energy balance, food intake, and lipid and glucose metabolism, through both central orexigenic effects and peripheral metabolic effects (4 -11). The endocannabinoid system is overactivated in genetic animal models of obesity (4, 6), and the selective CB-1 blocker, rimonabant, produces weight loss and ameliorates metabolic abnormalities in obese animals (12, 13). Patients with obesity and hyperglycemia associated with type 2 diabetes exhibit higher concentrations of endocannabinoids in the visceral fat and serum, respectively, than the corresponding controls (14). Rimonabant has been shown to produce substantial weight loss and reduction of waist circumference and also improve insulin resistance and the profile of several metabolic and cardiovascular risk factors in diabetic as well as nondiabetic obese patients (15)(16)(17)(18).Adiponectin is an adipokine ...

BackgroundA growing body of anecdotal evidence indicates that the use of robots may provide unique opportunities for assisting children with autism spectrum disorders (ASD). However, previous studies investigating the effects of interventions using robots on joint attention (JA) in children with ASD have shown insufficient results. The robots used in these studies could not turn their eyes, which was a limitation preventing the robot from resembling a human agent.MethodsWe compared the behavior of children with ASD with that of children with typical development (TD) during a JA elicitation task while the children interacted with either a human or a robotic agent. We used the robot “CommU,” which has clear eyes and can turn its eyes, for the robotic intervention. The age range of the participants was limited to 5–6 years.ResultsSixty-eight participants participated in this study, including 30 (10 females and 20 males) children with ASD and 38 (13 females and 25 males) children with TD. The participants were randomly assigned to one of the following two groups: the robotic intervention group or the control group. JA in the children with ASD was better during the robotic intervention than during the human agent intervention. These children exhibited improved performance in the JA task with human after interacting with the robot CommU. JA was differentially facilitated by the human and robotic agents between the ASD and TD children.ConclusionsThe findings of this study significantly contribute to the literature on the impact of robots on JA and provide information regarding the suitability of specific robot types for therapeutic use.Electronic supplementary materialThe online version of this article (10.1186/s13229-018-0230-8) contains supplementary material, which is available to authorized users.

The relationship between language development in early childhood and the maturation of brain functions related to the human voice remains unclear. Because the development of the auditory system likely correlates with language development in young children, we investigated the relationship between the auditory evoked field (AEF) and language development using non-invasive child-customized magnetoencephalography (MEG) in a longitudinal design. Twenty typically developing children were recruited (aged 36-75 months old at the first measurement). These children were re-investigated 11-25 months after the first measurement. The AEF component P1m was examined to investigate the developmental changes in each participant's neural brain response to vocal stimuli. In addition, we examined the relationships between brain responses and language performance. P1m peak amplitude in response to vocal stimuli significantly increased in both hemispheres in the second measurement compared to the first measurement. However, no differences were observed in P1m latency. Notably, our results reveal that children with greater increases in P1m amplitude in the left hemisphere performed better on linguistic tests. Thus, our results indicate that P1m evoked by vocal stimuli is a neurophysiological marker for language development in young children. Additionally, MEG is a technique that can be used to investigate the maturation of the auditory cortex based on auditory evoked fields in young children. This study is the first to demonstrate a significant relationship between the development of the auditory processing system and the development of language abilities in young children.

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Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variability have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynamics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age‐related increase of brain signal variability in a specific timescale in TD children, whereas atypical age‐related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was confirmed particularly for younger children. In the ASD group, symptom severity was associated region‐specifically and timescale‐specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural connectivity in ASD, especially during early childhood. Results of this study suggest that MSE analytic method might serve as a useful approach for characterizing neurophysiological mechanisms of typical‐developing and its alterations in ASD through the detection of MEG signal variability at multiple timescales. Hum Brain Mapp 37:1038–1050, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.