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Aging is associated with a progressive decrease in appetite and food intake. Both A and B orexins, expressed in specific neurons of the lateral hypothalamic area, have been implicated in the regulation of sleep and feeding. In this study, the stimulatory effect of intracerebroventricular administration of the orexins on food intake was compared between young (4-mo-old) and old (25- to 27-too-old) male Wistar rats. A stainless steel cannula was implanted stereotactically into the left lateral ventricle. After a 7-day recovery period, different doses (0-30 nmol) of orexins were injected into the left lateral ventricle without anesthesia. Food and water consumptions were measured at 1, 2, and 4 h after injection. The protein levels of orexin receptors, a specific receptor for orexin-A (OX1R) and a receptor for both orexin-A and -B (OX2R), in the hypothalamus were determined by Western blot analysis and compared between young and old rats. Intracerebroventricular administration of orexin-A stimulated food intake in a dose-dependent manner in young rats. However, no effects were observed at any dose in old rats. The protein level of OX 1R in the hypothalamus was significantly lower in old rats than in young rats, although the protein level of OX2R was comparable between groups. Results of the present study indicate that the function of the orexin system is diminished in old rats. The decrease in the OX1R protein level in the hypothalamus could be responsible for orexin-A's lack of stimulation of food intake in old rats. age; anorexia of aging; brain; hypothalamus; orexin receptor

The circadian rhythm of the body core temperature ([T.sub.c]) and the effects of changes in ambient temperatures on the homeostasis of [T.sub.c] in Otsuka Long Evans Tokushima Fatty (OLETF) rats, which are naturally occurring cholecystokinin (CCK)-A receptor (CCK-AR) gene knockout (-/-) rats, were examined. In addition, the peripheral responses to warming or cooling of the preoptic and anterior hypothalamic region (PO/AH) were determined. The circadian rhythm of [T.sub.c] in OLETF rats was similar to that in Long-Evans Tokushima (LETO) rats; this rhythm was characterized by a higher [T.sub.c] during the dark period and a lower [T.sub.c] during the light period. When the ambient temperature was changed within the limits of 0[degrees]C to 30[degrees]C, the changes in [T.sub.c] of LETO rats were associated with the changes in ambient temperature, whereas those in OLETF rats were dissociated from the temperature changes. The OLETF rats showed a large hysteresis. The peripheral responses to warming or cooling of PO/AH, including shivering of the neck muscle and changes in skin temperature of the tail and footpad, were similar in OLETF and LETO rats. To confirm the role of CCK-AR in the regulation of body temperature, the values of [T.sub.c] in the CCK-AR(-/-) mice were compared with those in CCK-B receptor (CCK-BR) (-/-), CCK-AR(-/-)BR (-/-), and wild-type mice. In the mice, the circadian rhythms of [T.sub.c] were the same, regardless of the genotype. Mice without CCK-AR showed larger hysteresis than mice with CCK-AR. From these results, we conclude that the lack of CCK-AR causes homeostasis of [T.sub.c] in rats and mice to deteriorate. knockout mice

Increased lymphatic lipid transport in genetically diabetic obese rats. Am J Physiol Gastrointest Liver Physiol 282: G69-G76, 2002.--Otsuka Long-Evans Tokushima fatty (OLETF) rats are a model for noninsulin-dependent diabetes mellitus (NIDDM), which is first manifested at 18 wk of age. We assessed age-related changes in lymphatic lipid transport in the intestine of OLETF rats and compared them with those of control Long-Evans Tokushima Otsuka (LETO) rats. Olive oil was infused into the rats with a mesenteric lymph fistula, which was created under ethrane anesthesia. A significant increase in lymphatic triglyceride (TG) transport in OLETF rats was observed at 18-19 wk compared with under 17 wk, but no age-related change was observed in LETO rats. Food restriction, exercise training, or troglitazone treatment in OLETF rats prevented the age-related increase in lipid transport. Biliary phosphatidylcholine concentration was higher in OLETF rats than in LETO rats, but no difference was seen in bile acid concentrations or the activity of microsomal TG transfer protein between the two strains. This study shows that increased lipid transport in the intestine may occur in NIDDM. lymph fistula rats; noninsulin-dependent diabetes mellitus; triglyceride; biliary phosphatidylcholine; troglitazone

A study was conducted to analyze changes in the levels of novel luminal cholecystokinin-releasing factor (LCRF) in the small intestinal lumen before and after bile-pancreatic juice diversions in rats. A specific radioimmunoassay was utilized to carry out the analysis. Anti-LCRF antiserum was raised in rabbits as a sensitive radioimmunoassay was established.The locationalization of LCRF was then analyzed by immunohistochemistry.

Second filial generation crosses of the Otsuka Long-Evans Tokushima (OLETF) rats were used in the genetic analyses of two loci postulated to cause diabetes in rats. OLETF rats show characteristics of human non-insulin dependent diabetes mellitus. Results of the breeding studies reveal that rats containing the knock out cholecystokinin type A receptor (CCKAR) had high plasma glucose levels. This gene was mapped close to the ODB2 gene, one of two genes that cause diabetes. The CCKAR gene appears to act synergistically with the ODB1 gene to induce diabetes.

Research was conducted to study the function and peripheral mechanism of action of central dopamine on basal pancreatic exocrine secretion in rats. Bile and pancreatic juices were collected for 30-min periods while dopamine was intracerebroventricular administered in vagotomized rats. Results indicated that propranolol inhibited basal pancreatic fluid and protein secretion while bretylium and phentolamine had no effect. They also showed that the inhibitory effect of dopamine was inhibited by phentolamine.

The effects of somatostatin on exocrine pancreatic secretion stimulated by vagal nerve efferent excitation was analyzed in conscious Wistar rats. Intracerebroventricular injections of somatostatin in rats inhibited pancreatic secretions that were induced by thyrotropin-releasing hormones (TRH). Somatostatin also inhibited vagal afferent nerve excitation that was mediated by TRH. Furthermore, 2-deoxy-D-glucose and TRH promote pancreatic secretion by stimulating the vagal efferent nerve via distinct pathways.

Background. Cholecystokinin (CCK) is an important bioactive peptide which stimulates pancreatic enzyme secretion and is also a neuromodulator in the central nervous system. We examined whether CCK release from the central and peripheral tissues was decreased in old animals, and whether there were sex-related differences. Methods. Young (5-10-month-old) and old (25-29-month-old) male and female Wistar rats were used. Synaptosomes were prepared from the cerebral cortex, and the vasculary perfused duodenojejunum was isolated to examine central and peripheral CCK release, respectively. In some young female rats, 21 days after bilateral ovariectomy, the peripheral CCK release and the changes in CCK mRNA levels were examined. Results. The central CCK release was impaired in response to the higher concentration of KCI, and the peripheral CCK response to the highest dose of neuromedin C was impaired in old male rats. However, no aging effect was observed in female rats, and ovariectomy did not affect CCK release or CCK mRNA level. Conclusions. CCK release from both central and peripheral tissues was decreased in old male rats, but not in old female rats.

Cholecystokinin (CCK) is an important gastrointestinal hormone as well as a neurotransmitter. Two types of CCK receptors, types A and B, have been identified. The CCK-A receptor is involved in satiety, food intake and behavior, whereas the B receptor is involved in anxiety. We recently produced CCK-A, -B and AB receptor knockout mice to study the role of these receptors in energy metabolism. Daily energy intake and expenditure were significantly greater in CCK-BR(-/-) and CCK-AR(-/-) BR(-/-) mice than CCK-AR(-/-) and wild-type [CCKAR(+/+)BR(+/+)] mice. Relative liver and kidney weights (g/kg body) were significantly greater in CCK-AR(-/-) BR(-/-) mice than in wild-type mice. Energy metabolism and energy turnover were increased in mice with a disruption of the CCK-BR gene, although the underlying mechanism is unknown. J. Nutr. 132: 739-741, 2002. KEY WORDS: * energy expenditure * energy intake * energy metabolism * knockout mice * cholecystokinin-receptor

Otsuka Long Evans Tokushima Fatty (OLETF) rats were developed as a model of noninsulin-dependent diabetes mellitus (NIDDM) with mild obesity. Changes in carcass composition and in the daily profile of energy expenditure were examined before and after manifestation of diabetes (8 and 24 wk, respectively), and compared with the normal control Long Evans Tokushima (LETO) rats and streptozotocin (STZ)-induced diabetic LETO rats. OLETF rats had greater body weights than LETO rats and significantly greater absolute and relative fat weights. A diurnal rhythm of energy expenditure associated with two peaks was observed in LETO rats, but the two peaks were not apparent in OLETF rats at 24 wk of age. A diurnal rhythm associated with one peak was observed in STZ-induced diabetic LETO rats. Energy derived from fat constituted this peak; the pattern of the daily energy expenditure was significantly different from that of either nontreated LETO or OLETF rats at 24 wk of age. NIDDM in OLETF rats at 24 wk of age has only a small role in modification of the diurnal rhythm of energy expenditure, whereas STZ-induced diabetes significantly affected the rhythm. J. Nutr. 130: 2562-2567, 2000. KEY WORDS: * energy expenditure * insulin resistance * diurnal rhythm * insulin-dependent diabetes mellitus * obesity * rats