Yoshiyuki Azuma

Effects of central administration of glucagon on feed intake and endocrine responses in sheep.

This study was conducted to investigate effects of glucagon intracerebroventricularly administered on feed intake and endocrine changes in sheep. Four male sheep (48-55 kg BW) were used. The animals were acclimatized to be fed alfalfa hay cubes at 12.00 hour. Human glucagon (40 and 80 microg/0.5 mL) was injected into the lateral ventricle at 12.00 hour. Blood samples were taken every 10 min from 30 min before to 180 min after the glucagon injection. Soon after the injection, the animals were given alfalfa hay cubes, and the amounts of the feed eaten within 2 h were measured. Feed intakes were significantly (P < 0.05) suppressed by 80 microg of glucagon. Plasma glucose levels in control animals were gradually decreased after the feeding, whilst those in glucagon-treated animals were temporarily elevated just after the feeding and then kept higher than control levels. Plasma insulin was abruptly elevated after the feeding and was maintained at higher levels than before the feeding in all treatments. Plasma NEFA concentrations were decreased after the feeding in all treatments. A tendency of increase in plasma cortisol levels occurred in glucagon-injected animals. The present study provides the first evidence that glucagon directly acts on the brain, then inhibiting feeding behavior and inducing endocrine responses in ruminants.

Ghrelin differentially modulates the GH secretory response to GHRH between the fed and fasted states in sheep

The effect of energy balance on the growth hormone (GH) secretory responsiveness to growth hormone-releasing hormone (GHRH) has not been determined in ruminant animals. Therefore, we examined the effects of intravenous injections of 0, 3.3, and 6.6 microg ghrelin/kg body weight (BW), with and without GHRH at 0.25 microg/kg BW, on GH secretory responsiveness in both the fed and fasted sheep. The injections were carried out at 48 h (Fasting state) and 3h (Satiety state) after feeding. Blood samples were taken every 10 minutes, from 30 minutes before to 120 minutes after the injection. Low (3.3 microg/kg BW) and high (6.6 microg/kg BW) doses of ghrelin stimulated GH secretion significantly (P<.05) greater in the Satiety state than in the Fasting state. Growth hormone-releasing hormone plus both doses of ghrelin stimulated GH secretion significantly (P<.05) greater in the Satiety state than in the Fasting state. Ghrelin and GHRH exerted a synergistic effect in the Satiety state, but not in the Fasting state. Plasma ghrelin levels were maintained significantly (P<.05) greater in the Fasting state than in the Satiety state except the temporal increases after ghrelin administration. Plasma free fatty acid (FFA) concentrations were significantly (P<.01) greater in the Fasting state than in the Satiety state. In conclusion, the present study has demonstrated for the first time that ghrelin differentially modulates GH secretory response to GHRH according to feeding states in ruminant animals.

The differences in feeding-inhibitory responses to peripheral and central leptin between non-lactating and lactating rats

This study was conducted to examine the contributions of central and peripheral leptin to hyperphagia in lactation. Lactating rats were mated at 7-8 weeks of age and housed singly with their litters. In experiment 1, food intakes were significantly (P<0.01) greater (350% on average) in lactation than in non-lactation throughout a day. Cerebrospinal fluid (CSF) leptin levels remained constant despite plasma leptin levels being significantly (P<0.05) greater in non-lactation than in lactation. In experiment 2, CSF leptin levels were not altered by i.v. injections of leptin (0.2 and 0.4 mg/kg body weight) despite that plasma leptin levels were dose dependently (P<0.01) increased. Moreover, i.v. administration of leptin significantly (P<0.05) decreased food intake in non-lactating rats but not in lactating rats. In experiment 3, nocturnal food intakes were temporarily (P<0.05) reduced in non-lactating and lactating rats. I.c.v. administration of a leptin antagonist (15 μg) blocked the reductions of food intakes. I.c.v. administration of leptin (10 μg) significantly (P<0.05) decreased cumulative food intakes during 24 h in both the physiological states. In conclusion, this study has presented new evidence that the hyperphagia of lactating rats could be partly due to depressed sensitivity of neurons contacting blood leptin. In contrast, the responsiveness of leptin receptors contacting CSF leptin may not differ between non-lactating and lactating rats. Furthermore, the levels of CSF leptin remained constant independent of those of blood leptin. Therefore, the expression of hypothalamic leptin receptors contacting CSF could be involved in the difference in food intake between non-lactating and lactating rats.

Changes in blood pancreatic polypeptide and ghrelin concentrations in response to feeding in sheep

The roles of pancreatic polypeptide (PP) have not been determined in ruminant animals. The aim of the present study was to examine the role of PP in the regulation of ghrelin secretion in sheep. Two experiments were conducted using four 2-yr-old Suffolk wethers fed a maintenance diet of alfalfa hay cubes. In Exp. 1, the effects of feeding on blood ghrelin and PP concentrations were examined in scheduled-fed sheep. Blood samples were collected every 10 min from 30 min before to 360 min after feeding. Plasma PP concentrations were transiently increased from the preprandial average value to the values from 30 to 60 min after feeding and gradually decreased (P < 0.05) to stable values from 150 to 180 min. The values from 30 to 60 min were greater (P < 0.05) than those from 150 to 360 min. In contrast, plasma ghrelin concentrations were gradually decreased (P < 0.01) by feeding. The values from 60 to 360 min were less (P < 0.01) than the preprandial average value. In Exp. 2, the effects of continuous PP infusion on ghrelin secretion were examined in feed-deprived sheep. The animals were deprived of feed for 48 h before PP infusion. The PP-treated group intravenously received synthetic bovine PP at a rate of 10 pmol.kg(-1 )of BW.min(-1) for 180 min. Blood samples were collected every 10 min from 30 min before to 180 min after the commencement of PP infusion. Plasma PP concentrations reached a plateau within 30 min after the commencement of PP infusion. Plasma ghrelin concentrations were decreased (P = 0.002, 0.016, 0.007) by PP infusion at 160, 170, and 180 min, respectively. In conclusion, plasma ghrelin and PP concentrations were decreased and increased, respectively, in response to feeding in ruminant animals. Furthermore, PP could depress ghrelin secretion.

Egg White Hydrolysate Can Be a Low-Allergenic Food Material to Suppress Ectopic Fat Accumulation in Rats Fed an Equicaloric Diet

Egg white (EW) is known as a nutritional protein but can induce allergic reactions in humans. We investigated the dietary effects of EW and its hydrolysate (EWH), which contains less allergen, on body fat accumulation in Wistar rats fed an equicaloric high-fat and high-sucrose diet for 8 wk (Exp A). The pair-feeding of EW and equicaloric-feeding of EWH increased fecal fat excretion and suppressed lipid accumulation in the liver and muscles but not in the abdominal adipose tissues, carcass, or total body. Dietary EWH also suppressed the serum glucose level and alkaline phosphatase activity. Further, we showed a higher dispersibility of EW and EWH in physicochemical assay (Exp B). Next, we investigated the suppressive effects of a single administration of EW and EWH on lipid-induced hypertriglyceridemia and small intestinal meal transit in ddY mice (Exp C). However, a single administration of EW or EWH did not suppress the lipid-induced hypertriglyceridemia nor did it delay the rate of small intestinal transit. These findings indicated that dietary EW and EWH reduce hepatic and muscular (ectopic) fat accumulation mainly by suppressing fat absorption and supplying fat to the liver and muscles. Therefore, the low-allergenic EWH can be effective for the prevention of high-fat-diet-induced obesity.

Egg White Hydrolysate Improves Glucose Tolerance in Type-2 Diabetic NSY Mice

We have previously reported that chicken egg white (EW) and low-allergenic EW hydrolysate (EWH) suppressed ectopic fat accumulation and improved serum glucose and insulin levels. In this study, the dietary effects of EW and EWH on glucose tolerance were investigated in different ways to clarify the effect of EW and EWH on intestinal glucose absorption. Type 2 diabetic Nagoya-Shibata-Yasuda mice were divided into four groups: a low-fat and low-sucrose casein-based diet group (NL); high-fat and high-sucrose (HFS) casein-based diet group (NH); HFS EW-based diet group (NE); and HFS EWH-based diet group (NEH). Mice were fed their respective diets for 8 wk. At the end of the 6th and 7th week, an oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were respectively conducted in experiment A. At the end of the 7th week, an intraperitoneal glucose tolerance test (ipGTT) was conducted in experiment B. In experiment A, the plasma glucose level was suppressed in the NE group during both OGTT and ITT, and suppressed in the NEH group during OGTT, but not during ITT. In experiment B, the plasma glucose level was similarly suppressed in the NEH group during ipGTT, but the suppressive effect was weakened compared to OGTT. Plasma insulin level was lower in the NE and NEH groups in both experiments. Fecal triacylglycerol excretion was increased in the NE and NEH groups in experiment A and liver triacylglycerol content was suppressed in the NE group in experiment B. These findings suggested that in addition to improving fat metabolism, EWH improves glucose tolerance via mechanisms related and unrelated to small intestinal function.