In developed and developing countries, morbidity and mortality rates are increasing in individuals classified as being obese [1-6]. The higher morbidity and mortality rates of obese people are due to the increased incidence of obesity-related (lifestyle-related) diseases. It is now recognized that different criteria of obesity by BMI are necessary in different ethnic groups and populations [7,8]. In addition to the degree of obesity, other factors which increase the morbidity rate of obese people include abnormal fat distribution such as upper body obesity and visceral obesity [9,10]. Recently, the definition of 'pathological obesity' has been made in Japan [11]. Definition of Obesity and Previous Criteria of ObesityObesity is defined as excessive fat accumulation but not over-weightedness. The average human body usually consists of 82% lean body mass, which is essential for sustaining daily life and physical activities, and 18% body fat which, in essence, is energy store for emergency situations [12]. Thus, obesity can be defined as 'overstorage of body fat beyond 18%'. Usually, body fat above 25% in men and 30% in women is considered to be obese. According to this definition, obesity should be determined by measuring body fat. Although there are presently many methods for measuring body fat, no methods can be conducted easily, accurately and inexpensively.

The site of action for the sleep-promoting effect of prostaglandin (PG) D2 was extensively examined in the brain of adult male rats (n = 231). PGD2 was administered at 100 pmol/0.2 pI per min for 6 hr (2300-0500 hr) through chronically implanted microdialysis probes or infusion cannulae. Among the administrations of PGD2 by dialysis probes (n = 176), only those (n = 8) to a ventro-rostral part of the basal forebrain by the probes implanted on the midline consistently increased slow-wave sleep (SWS), by 51 ± 6 min (mean ± SEM) above the baseline value (111 ± 11 min). Since this area is separated by a cleft into right and left regions, the results were interpreted to mean that, through this cleft, PGD2 diffused in the subarachnoid space over the adjacent ventral surface, where it had the effect ofpromoting sleep. When PGD2 was directly infused into the subarachnoid space (n = 55), extraordinary increases exceeding 90 min were consistently attained for the SWS at sites located between 0.5 and 2 mm rostral to the bregma and between 0 and 1.2 mm lateral to the midline defined according to the stereotaxic coordinates adopted from the brain atlas of Paxinos and Watson [Paxinos, G. & Watson, C. (1986) The Rat Brain in Stereotaxic Coordinates (Academic, San Diego)]. Thus, we demarcated a "PGD2-sensitive, sleep-promoting zone" within this region in the ventral surface of the rostral basal forebrain. During the bilateral infusion of PGD2 into the subarachnoid space of this zone, the hourly mean SWS level of the nocturnal animals (n = 6) in the night reached the maximum at the second hour of the infusion period; this maximum hourly SWS level, corresponding to the daytime level of the same animals, lasted until the end of PGD2 infusion.Prostaglandin D2 (PGD2) has been postulated as one of the endogenous sleep-promoting substances in rats and other mammals including humans (1). PGD2 has been implicated in the physiological regulation of sleep by the fact that sleep in rats was markedly suppressed by intracerebroventricular (2) or intravenous (3) administration of inorganic selenium compounds, which are inhibitors of PGD synthase (EC 5.3.99.2), the enzyme responsible for the synthesis of PGD2 in the rat brain (4).The preoptic area (POA) has long been proposed as a sleep center since the experimental study by Nauta in 1946 (5). The site of action for the sleep-promoting effect of PGD2 has been postulated to be located in or near the POA since an increase in the amount of sleep was first demonstrated with PGD2 in 1982 by a microinjection study (6). Subsequent studies in monkeys (7) and rats (8) also supported the assumption that the site of action is located in a rostral and ventral region, adjacent to the third cerebral ventricle; however, the exact site of action has not yet been clearly defined.In this paper, the site most effective in promoting sleep with PGD2 administration was extensively studied by use of the microdialysis technique and the continuous infusion method. The results clearly define the site of action ...

Osaka, Toshimasa. Cold-induced thermogenesis mediated by GABA in the preoptic area of anesthetized rats. Am J Physiol Regul Integr Comp Physiol 287: R306 -R313, 2004. First published March 18, 2004 10.1152/ajpregu.00003.2004.-Bilateral microinjections of GABA (300 mM, 100 nl) or the GABA A receptor agonist muscimol (100 M, 100 nl) into the preoptic area (POA) of the hypothalamus increased the rate of whole body O 2 consumption (V O2) and the body core (colonic) temperature of urethane-chloralose-anesthetized, artificially ventilated rats. The most sensitive site was the dorsomedial POA at the level of the anterior commissure. The GABA-induced thermogenesis was accompanied by a tachycardic response and electromyographic (EMG) activity recorded from the femoral or neck muscles. Pretreatment with muscle relaxants (1 mg/kg pancuronium bromide ϩ 4 mg/kg vecuronium bromide iv) prevented GABAinduced EMG activity but had no significant effect on GABA-induced thermogenesis. However, pretreatment with the ␤-adrenoceptor propranolol (5 mg/kg iv) greatly attenuated the GABA-induced increase in V O2 and tachycardic responses. Accordingly, the GABA-induced increase in V O2 reflected mainly nonshivering thermogenesis. On the other hand, cooling of the shaved back of the rat by contact with a plastic bag containing 28°C water also elicited thermogenic, tachycardic, and EMG responses. Bilateral microinjections of the GABA A receptor antagonist bicuculline (500 M, 100 nl), but not the vehicle saline, into the POA blocked these skin cooling-induced responses. These results suggest that GABA and GABA A receptors in the POA mediate cold information arising from the skin for eliciting coldinduced thermogenesis. thermoafferent; neurotransmitter; nonshivering thermogenesis THE PREOPTIC AREA (POA) of the hypothalamus is considered to be the primary locus for body temperature regulation, because it integrates thermoafferent signals from the skin and other parts of the body and exerts control over the thermoefferent mechanisms (3,8,15,25). However, the neurotransmitter that mediates thermoafferent signals to the POA is largely unknown, even though there is a great deal of electrophysiological and pharmacological evidence implicating a role for a variety of neurotransmitters, peptides, and cytokines (2, 6, 10, 32).The POA contains GABAergic neurons (27), spontaneously releases GABA to the extracellular space (9, 29), and expresses GABA A receptors (7). Perfusion of the POA with the GABA A agonist muscimol induces hyperthermia, which is not affected by antipyretics and is thus independent of fever, in freely behaving rats (19). Warm-sensitive and thermally insensitive neurons are inhibited by the GABAergic mechanism in the POA (28). Furthermore, it was recently reported that the extracellular GABA level in the POA was increased by acute cold exposure and decreased by heat exposure (14). Therefore, it is possible that GABA is involved in the mechanism of thermoregulation in the POA.Body temperature is regulated by the balance between heat ...

Proinflammatory cytokines including interleukin (IL)-1 and IL-6 exert pleiotropic effects on the neuro-immunoendocrine system. Previously, we showed that IL-1 receptor antagonist-deficient (IL-1Ra ؊/؊ ) mice show a lean phenotype due to an abnormal lipid metabolism. On the contrary, it was reported that IL-6 ؊/؊ mice exhibit obesity after 6 months of age. This study sought to assess the roles of IL-1 and IL-6 in body weight homeostasis. We generated mice deficient in IL-6 and IL-1Ra (IL-6 ؊/؊ IL-1Ra

Subcutaneous administration of capsaicin (5 mg/kg) immediately increased the temperature of the tail skin (Tsk) for 2 h in urethan-anesthetized rats, suggesting an increase in heat loss. O2 consumption, an index of heat production, also immediately increased after the capsaicin injection, and this increase lasted for >10 h. Colonic temperature (Tco) decreased within 1 h after the injection, and this decrease was followed by a long-lasting hyperthermic period. Adrenal demedullation largely attenuated the capsaicin-induced increase in O2consumption, and sympathetic denervation of the interscapular brown adipose tissue partly attenuated the increase in O2 consumption. However, capsaicin-induced heat loss was normal in these rats. In rats with cutaneous vasodilation maximized by warming and administration of hexamethonium, capsaicin did not further increase Tsk but normally induced heat production, and Tco gradually rose without a hypothermic period. Thus capsaicin simultaneously increased heat loss and heat production, and inhibition of one response did not affect the other. These findings suggest that capsaicin simultaneously activates independent networks for heat loss and heat production.

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