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Several reports have demonstrated that neuropeptide Y (NPY) is involved in food intake, epilepsy, circadian rhythms, drug seeking, pain and anxiety, and other physiological or pathological conditions. On the other hand, periaqueductal gray (PAG) is a key brain center for modulating pain, anxiety and fear. It is the main structure implicated in integrated defensive behaviors. One such behavior, tonic immobility (TI), resembles fear and is able to induce analgesia. After microinjection of [Leu 31 ,Pro 34 ]-Neuropeptide Y ([Leu 31 ,Pro 34 ]-NPY) into the PAG dorsal (D) or ventrolateral (VL) of adult male Wistar rats, the following parameters were assessed: i) the analgesic effect by means of the tail-flick test (TF), ii) the duration of TI as a passive defensive behavioral response and as an anxiety/fear model (considering both TF and TI as single behaviors), iii) TI-induced analgesia by the combination of TF/TI, and iv) the anxious-like state through the elevated plus maze (EPM), and defensive burying behavior (DBB). The results show that the microinjection of [Leu 31 ,Pro 34 ]-NPY into the PAG produced an analgesic effect (increasing the TF latency); overall decreased the TI duration, which might represent an important anti-fear effect. Moreover, [Leu 31 ,Pro 34 ]-NPY microinjected into the PAG allows for a TI-induced analgesic effect, as well as, a substantial anxiolytic effect (evidenced by the EPM and DBB models). Hence, [Leu 31 ,Pro 34 ]-NPY microinjected into the PAG, especially at 0.47 nmol/0.5 μL produces both analgesic and anxiolytic effects, in a higher magnitude within ventrolateral area. [ABSTRACT FROM AUTHOR]

Abstract: Overweight and obesity have been associated with increase in cardiometabolic risk. Therapeutics include lifestyle changes and/or pharmacologic agents. However, such interventions are often limited by poor compliance and/or significant side effects. The consumption of certain dietary products, such as cocoa, exerts positive effects on cardiometabolic risk factors. (−)-Epicatechin (EPI), the most abundant flavonoid in cacao has been reported to replicate such effects. However its mechanisms of action have not been fully elucidated.In a rat model of high-fat diet-induced obesity and its associated crdiometabolic risk factors, we administered 1mg/kg of EPI, by gavage, for 2 weeks. Endpoints included weight-gain, glycemia, triglyceridemia, and systolic blood pressure. We also assessed food intake and fecal excretion. Mitochondrial function and structure related proteins were measured by Westerns.Obesity, hyperglycemia, hypertriglyceridemia, and systolic hypertension were developed after the administration of the high-fat diet for five weeks. EPI significantly decreased the rate of weight gain, glycemia and hypertriglyceridemia. The ratio between energy intake and excretion was not significantly modified by treatment. EPI restored the obesity-induced decreases in the levels of skeletal muscle and abdominal tissue sirtuins (SIRTs), peroxisome proliferator-activated receptor coactivator (PGC-1α), mitofilin, transcription factor A mitochondrial (TFAM), uncoupling protein 1 (UCP1), and deiodinase.EPI treatment yielded beneficial effects on high fat diet-induced endpoints thus may be considered as a potential agent for the treatment of obesity and its cardiometabolic associated abnormalities. Mechanism of action may be attributed to the modulation of cellular/mitochondrial function, thus improving overall metabolism. [Copyright &y& Elsevier]