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Same kind of initiators employ different types of cytokines to mediate the same endocrinological activation. Cytokines, in addition to possessing undivided control mechanisms for their generation and release, exert complex actions, thus influencing the production and function of other cytokines. Host defense mechanisms require cytokines such as TNF-alpha to activate the hypothalamic-pituitary-adrenal axis.

Obesity is a critical risk factor for the development of metabolic syndrome, and many obese animal models are used to investigate the mechanisms responsible for the appearance of symptoms. To establish a new obese mouse model, we screened ∼13,000 ICR mice and discovered a mouse demonstrating spontaneous obesity. We named this mouse "Daruma" after a traditional Japanese ornament. Following the fixation of the genotype, these animals exhibited obese phenotypes according to Mendel's law of inheritance. In the Daruma mouse, the leptin receptor gene sequence carried two base mutations that are good candidates for the variation(s) responsible for the obese phenotype. The Daruma mice developed characteristic visceral fat accumulation at 4 wk of age, and the white adipose and liver tissues exhibited increases in cell size and lipid droplets, respectively. No histological abnormalities were observed in other tissues of the Daruma mice, even after the mice reached 25 wk of age. Moreover, the onset of impaired leptin signaling was early and manifested as hyperleptinemia and hyperinsulinemia. Pair feeding completely inhibited obesity, although these mice rapidly developed hyperphagia and obesity followed by hyperleptinemia when pair feeding ceased and free-access feeding was permitted. Therefore, the Daruma mice exhibited unique characteristics and may be a good model for studying human metabolic syndrome.

Neuromedin U (NMU) is a hypothalamic peptide involved in energy homeostasis and stress responses. NMU, when administered intracerebroventricularly, decreases food intake and body weight while increasing body temperature and heat production. In addition, NMU, acting via the corticotropin-releasing hormone (CRH) system, induces gross locomotor activity and stress responses. We studied the effect of intracerebroventricularly administered NMU (0.5-4 nmol) in the regulation of gastric functions in conscious rats. Intracerebroventricular administration of NMU significantly decreased gastric acid output to 30-60% and gastric emptying to 35-70% in a dose-dependent manner. Vagotomy did not abolish the inhibitory effect of NMU on pentagastrin-induced gastric acid secretion. Pretreatment with indomethacin (10 mg/kg), an inhibitor of prostaglandin synthesis, also did not affect NMU-induced acid inhibition. Pretreatment with anti-CRH IgG (1 microg/rat), however, completely blocked NMU-induced acid inhibition (P < 0.01). Administration of yohimbine (4 mg/kg), an alpha(2)-adrenergic receptor antagonist, also abolished NMU-induced acid inhibition (P < 0.01). These findings suggest that NMU is critical in the central regulation of gastric acid secretion via CRH.

The cardiovascular and humoral responses to sustained muscle metaboreflex activation were examined in eight male volunteers while they performed two 24-min exercise protocols. Each of these consisted of six 1-min bouts of isometric handgrip exercise (the left and right hands being used alternately) at 50% of maximal voluntary contraction; after each bout, there was either 3-min postexercise occlusion (occlusion protocol) or 3-min rest (control protocol). In the occlusion protocol, mean arterial blood pressure was approximately 25 mmHg higher than during the control protocol, indicating that the muscle metaboreflex was activated during occlusion. During the control protocol, plasma renin activity, plasma vasopressin, and adrenocorticotropic hormone values were not significantly different from the values at rest. During the occlusion protocol, however, plasma renin activity, plasma vasopressin, and adrenocorticotropic hormone were all significantly increased at 25 min. These data demonstrate that, in humans, the sustained activation of the muscle metaboreflex causes the secretion of several hormones originating from different regions.