Biomedical subjects

T A Lutz

Publications and source records attributed to T A Lutz.

At least 19 recordsLinked to original sources

PubMed2005

The orexigenic effect of peripheral ghrelin differs between rats of different age and with different baseline food intake, and it may in part be mediated by the area postrema.

Ghrelin is mainly secreted during fasting. While an orexigenic effect of peripherally injected ghrelin has been reported, reproducing this effect has often proven difficult. Here, we hypothesized that ghrelin's effect to increase food intake may depend on the experimental conditions (e.g., age of animals). We therefore investigated the effect of an IP ghrelin injection (100 microg/kg) on food intake in rats of different age and at different times during the light-dark cycle, i.e. with different levels of baseline food intake. Ghrelin injected at dark onset in ad libitum fed young rats (body weight [BW] 92 g) slightly increased feeding while no such effect was observed in 12 h food deprived rats (BW 150 g). In the middle of the light phase, ghrelin significantly increased feeding up to 2 h after injection in ad libitum fed rats (BW 130 g; food intake 1 h after injection: NaCl 0.4 +/- 0.2 g versus ghrelin 1.2 +/- 0.3 g [p < 0.05]). In various subsequent experiments, older rats (BW 300-490 g) tested under the same conditions did not respond to a single ghrelin injection. However repeated ghrelin injection (15 microg/kg/day once daily at light onset) over 10 days significantly increased food intake in rats (BW 400-460 g) starting from day 4 of the experiment (24 h food intake: NaCl approx. 19.5 g, ghrelin 22.5 g). Interestingly, the latter effect was completely abolished in rats lesioned in the area postrema (AP). Cumulative food intake was also increased in SHAM but not in AP-X animals (e.g., after 7 days: SHAM/NaCl 135.1 +/- 5.3 g versus SHAM/ghrelin 149.7 +/- 3.5 g [p < 0.05], AP-X/NaCl 127.2 +/- 16.4 versus AP-X/ghrelin 127.9 +/- 5.3). We conclude that ghrelin's effect to increase food intake can best be demonstrated when basal food intake is low. Ghrelin increases feeding mainly in young, fast growing animals. Ghrelin may therefore link the high energy needs to body growth in young individuals. In older animals, peripheral ghrelin increased feeding when injected repeatedly over several days. At least under these conditions, ghrelin's effect was mediated by the AP/NTS region. Using repeated administration, ghrelin might be an interesting tool to increase feeding in patients suffering from wasting diseases such as cancer anorexia.

Aging↗

PubMed2004

Effects of high carbohydrate and high fat diet on plasma metabolite levels and on i.v. glucose tolerance test in intact and neutered male cats.

To elucidate the impact of dietary influence on carbohydrate and lipid metabolism and on the development of diabetes mellitus in the carnivorous cat, a 3 weeks feeding trial was carried out on six sexually intact and six neutered adult male cats. The effects of two isonitrogenic diets, differing in carbohydrate and fat content, were investigated on plasma metabolite levels in a 24-h blood sampling trial. Plasma leptin concentrations were also determined at the beginning and at the end of the 24-h trial. Glucose and insulin response was measured in an i.v. glucose tolerance test. A 5 days long digestion trial was also performed, which revealed a high digestion capacity of both fat and carbohydrates in cats. The high fat diet induced a significant rise in the plasma triglyceride, FFA, beta-hydroxybutyrate and cholesterol concentration, while the elevation in the glucose level did not reach significance. In the glucose tolerance test no significant difference was found between the neutered and intact cats. However, independently of the sexual state, the cats on the high fat diet showed a slightly elongated glucose clearance and reduced acute insulin response to glucose administration. This is indicative of diminished pancreatic insulin secretion and/or beta-cell responsiveness to glucose. The results of this preliminary study may be the impetus for a long-term study to find out whether it is rather the fat rich ration than carbohydrate rich diet that is expected to impair glucose tolerance and thus might contribute to the development of diabetes mellitus in cats. Whether the alteration in glucose metabolism is due to altered leptin levels remains to be determined.

3-Hydroxybutyric Acid↗

PubMed2004

Inhibition of glucose oxidation by alpha-cyano-4-hydroxycinnamic acid stimulates feeding in rats.

Alpha-cyano-4-hydroxycinnamic acid (4-CIN, 100-200 mg/kg b.wt.), which impairs glucose oxidation by inhibiting pyruvate transport across the mitochondrial membrane, stimulated feeding in rats following intraperitoneal injection without affecting blood glucose level. Like 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, 4-CIN probably acts mainly on the CNS through activation of alpha(2)-adrenergic receptors, because the feeding response to 4-CIN was eliminated by phentolamine or yohimbine. Unlike feeding elicited by 2-DG, 4-CIN-induced feeding was eliminated by total abdominal (but not hepatic branch) vagotomy. Since peripheral atropinization also blocked 4-CIN-induced feeding, activation of central parasympathetic neurons seems to be involved in 4-CIN-induced feeding. The feeding response to 4-CIN was diminished in rats fed a high-fat diet, probably because metabolic sensors sensing fatty acid oxidation counteract the feeding response to 4-CIN. The results suggest that inhibition of glucose oxidation by blocking pyruvate entry into mitochondria stimulates feeding in rats in particular when fed a high-carbohydrate diet.

Adrenergic alpha-Antagonists↗

PubMed2003

The anorectic hormone amylin contributes to feeding-related changes of neuronal activity in key structures of the gut-brain axis.

Amylin is a peptide hormone that is cosecreted with insulin from the pancreas during and after food intake. Peripherally injected amylin potently inhibits feeding by acting on the area postrema (AP), a circumventricular organ lacking a functional blood-brain barrier. We recently demonstrated that AP neurons are excited by a near physiological concentration of amylin. However, the subsequent neuronal mechanisms and the relevance of endogenously released amylin for the regulation of food intake are poorly understood. Therefore, we investigated 1) amylin's contribution to feeding-induced c-Fos expression in the rat AP and its ascending projection sites, and 2) amylin's ability to reverse fasting-induced c-Fos expression in the lateral hypothalamic area (LHA). Similar to amylin (20 microg/kg sc), refeeding of 24-h food-deprived rats induced c-Fos expression in the AP, the nucleus of the solitary tract, the lateral parabrachial nucleus, and the central nucleus of the amygdala. In AP-lesioned rats, the amylin-induced c-Fos expression in each of these sites was blunted, indicating an AP-mediated activation of these structures. Pretreatment with the amylin antagonist AC-187 (1 mg/kg sc) inhibited feeding-induced c-Fos expression in the AP. Food deprivation activated LHA neurons, a response known to be associated with hunger. This effect was reversed within 2 h after refeeding and also in nonrefed animals that received amylin. In summary, our data provide the first evidence that feeding-induced amylin release activates AP neurons projecting to subsequent relay stations known to transmit meal-related signals to the forebrain. Activation of this pathway seems to coincide with an inhibition of LHA neurons.

Amyloid↗

PubMed2003

Endogenous amylin contributes to the anorectic effects of cholecystokinin and bombesin.

Previous studies indicated that amylin contributes to the anorectic effects of cholecystokinin (CCK) and bombesin (BBS), possibly by enhancing the release of pancreatic amylin or by modulating their anorectic actions within the central nervous system (CNS). To elucidate the interaction between amylin and CCK or BBS, respectively, we investigated the influence of an IP injection of CCK or BBS on feeding in amylin-deficient mice (IAPP(-/-)). The anorectic effects of CCK and BBS were nearly abolished in IAPP(-/-) mice compared to wildtype (WT) mice (e.g. 20 microg/kg CCK, 1-h food intake: WT/NaCl 0.53 +/- 0.03 g; WT/CCK 0.16 +/- 0.03 g (P < 0.001); IAPP(-/-)/NaCl 0.49 +/- 0.05 g; IAPP(-/-)/CCK 0.39 +/- 0.04 g). Acute amylin replacement restored the anorectic effect of CCK in IAPP(-/-) mice. To find out whether CCK or BBS enhance the feeding-induced release of pancreatic amylin, we injected rats with CCK-8 (0.5-50 microg/kg) or BBS (5 microg/kg) and measured plasma amylin levels after injections. Neither CCK nor BBS increased the plasma amylin level in rats. We suggest that the mediation of the anorectic effects of CCK and BBS by amylin is not dependent on a CCK- or BBS-induced release of pancreatic amylin, but may rather be due to a modulation of their effects by amylin within the CNS.

Amyloid↗

PubMed2002

Effects of amylin and salmon calcitonin on feeding and drinking behavior in pygmy goats.

In the present study, the effects of peripherally administered amylin and of the amylin-related peptide salmon calcitonin (sCT) on food and water intake was tested for the first time in pygmy goats. In the first series of experiments, the effect of amylin on food (0.5, 1.0 and 2.0 microg/kg b.wt.) and water (2.0 microg/kg) intake was tested. In the second series of experiments, the effect of sCT on food intake (1.0 microg/kg) was tested under ad libitum feeding conditions or after 14 h food deprivation. The relationship of dose on the effect of sCT (0.1, 0.5 and 1.0 microg/kg) on food and water intake was also tested. Finally, the effect of a low dose (0.1 sCT microg/kg) on water intake was also investigated during food withdrawal. We showed for the first time an anorexigenic effect of the satiety peptide amylin (2.0 microg/kg) in ruminants, which was characterized by a reduction in meal size. In pygmy goats, the administration of the three doses of sCT induced an anorexigenic effect, which was larger and of longer duration when compared with amylin, although the anorexigenic effect of the lowest dose never reached significance. This effect was not dose dependent and was partly due to a reduction in meal size and partly to a prolongation of the interval between meals. The anorexigenic effect of sCT was accompanied by a reduced water intake, probably due to reduced prandial drinking. Furthermore, the low dose of sCT (0.1 microg/kg) was dipsogenic during food withdrawal.

Amyloid↗

PubMed2001

Depolarization of the liver cell membrane by metformin.

Metformin (1,1-dimethylbiguanide; MET) is used in the treatment of type 2 diabetes mellitus. MET's antihyperglycemic action depends at least in part on its inhibitory effect on hepatic gluconeogenesis. As to gluconeogenesis from amino acids (e.g. L-alanine), this is associated with an inhibition of L-alanine uptake into hepatocytes. Since this uptake is mediated by an electrogenic transport mechanism, the aim of the present study was to investigate whether MET has an influence on the liver cell membrane potential which might explain its inhibitory effect on L-alanine uptake. The experiments were performed in vivo in anesthetized rats and in vitro using superfused mouse liver slices with the conventional microelectrode technique. In vivo, MET (160 mg/kg intraperitoneally (i.p.)) significantly depolarized (dV) the liver cell membrane by 6 mV. MET (1 mmol/l) also depolarized the liver cell membrane in vitro (e.g. 15 min after start of superfusion: dV=8 mV). MET's effect was at least partly reversible. Glucagon (10(-7) mol/l), which hyperpolarized the liver cell membrane, abolished MET's effect. Further, the MET-induced depolarization was completely absent during superfusion with low Cl(-) ([Cl(-)]=27 mmol/l) medium, and significantly attenuated by the Cl(-) channel blocker NPPB (25 micromol/l). While MET's effect was only somewhat attenuated by blockade of the Na(+)/K(+)/2Cl(-) cotransporter or by superfusion with (HCO(-)(3)-free) HEPES buffer, the carboanhydrase blocker acetazolamide (1 mmol/l) or blockade of the HCO(-)(3)/Cl(-) exchanger by DIDS (100 micromol/l), which, however, also blocks Cl(-) channels, abolished its effect. The depolarization of the liver cell membrane by MET was unaffected by a blockade of K(+) channels with Ba(2+), a blockade of the Na(+)/K(+) pump or superfusion with low Na(+) medium ([Na(+)]=26 mmol/l). According to these results, the MET-induced depolarization of the liver cell membrane could be due to an activation of the Cl(-)/HCO(-)(3) exchanger and thus depend on intracellular HCO(-)(3) formation. This activation could then lead to a disturbance of the equilibrium between intra- and extracellular Cl(-) and therefore to an enhanced Cl(-) efflux via Cl(-) channels. It is plausible that the depolarizing effect induced by MET is associated with its inhibitory effect on gluconeogenesis by inhibiting uptake of L-alanine and other amino acids into hepatocytes.

Animals↗

PubMed2001

The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema/nucleus of the solitary tract (AP/NTS) lesioned rats.

OBJECTIVE: Neurons in the area postrema/nucleus of the solitary tract (AP/NTS) region mediate amylin's anorectic effect elicited by a single intraperitoneal (i.p.) injection of a low dose (5 microg/kg). Here, we tested if a sustained elevation in amylin levels which was achieved by chronic amylin infusion reduces food intake by acting in the AP/NTS region or, possibly, at other brain sites. Further, we tested the role of the AP/NTS region in mediating the anorectic effects of high doses of amylin and its receptor agonist salmon calcitonin (sCT) after an acute single injection. DESIGN: Amylin (2 microg/kg/h) was chronically infused i.p. by osmotic minipumps in AP/NTS-lesioned (AP-X) or sham-lesioned (SHAM) rats. For the acute experiments, amylin or sCT was injected i.p. at doses of 0.5 (only sCT), 5 or 50 microg/kg. Food intake was measured by a computerized system. Body weight was assessed by manually weighing the rats. RESULTS: Amylin significantly reduced cumulative food intake for about 7 days in SHAM but not in AP-X rats. Amylin's effect in SHAM rats was mainly due to a reduction of the size of nocturnal meals (eg average meal size during the first four dark phases; SHAM, NaCl 4.1+/-0.6 vs amylin 2.6+/-0.4 g; n=6, P<0.05; AP-X, 2.6+/-0.3 vs 3.7+/-0.3) while light phase food intake was unaffected. Body weight gain over the whole 14 day infusion period was reduced by amylin in SHAM (NaCl 61+/-6 vs amylin 46+/-4 g; P<0.05) but not in AP-X rats (54+/-4 vs 62+/-4). After single injection, the anorectic effect of high doses of amylin and sCT (50 microg/kg) was attenuated, but not abolished, in AP-X rats. CONCLUSION: We conclude that, under our experimental conditions, neurons in the AP/NTS region are necessary for chronically elevated peripheral amylin to reduce food intake in rats. High doses of amylin, however, may be able to overrun these receptors and reduce feeding by acting at other brain sites.

Afferent Pathways↗

PubMed2001

Effects of mercaptoacetate on feeding, circulating glucose and lipids, and gastric emptying in rats fed a carbohydrate-free high-fat diet.

In the present study we investigated whether glucose deprivation contributes to feeding induced by mercaptoacetate (MA), an inhibitor of fatty acid oxidation, in Sprague-Dawley rats fed a carbohydrate-free, high-fat diet (HF-rats). The results show that inhibition of fatty acid oxidation by MA, reflected by a decrease in plasma beta-hydroxybutyrate, elicited eating in the HF-rats and that the eating response was not associated with a decrease in circulating glucose. The effect of MA on food intake was tested in two different substrains (Zur:SD and Ico:OFA SD) of Sprague-Dawley rats. The threshold dose of MA for eliciting eating was much higher in Zur:SD (between 800 and 1,600 micromol/kg) in comparison to Ico:OFA SD rats (between 200 and 400 micromol/kg). At a high dose of MA (1,200 micromol/kg), but not at a low dose (400 micromol/kg) the feeding response in the Ico:OFA SD rats was associated with hyperglycemia due to an increase in glycogenolysis. Unlike in Zur:SD, in Ico:OFA SD rats the higher doses of MA (800 and 1,200 micromol/kg but not 400 micromol/kg) produced a long-term suppression of feeding, which partly might be causally related to the observed inhibitory effect of MA on gastric emptying. The present results indicate that glucose deprivation does not contribute to feeding elicited by MA-induced inhibition of fatty acid oxidation in rats fed a carbohydrate-free, high-fat diet.

3-Hydroxybutyric Acid↗

PubMed2001

Dopamine D(2) receptors mediate amylin's acute satiety effect.

The anorectic effect of the pancreatic peptide amylin has been established in numerous studies. Here, we investigated the influence of a pretreatment with dopamine (DA) D(1)- and D(2)-receptor antagonists on the anorectic effect of intraperitoneally injected amylin in rats fed a medium-fat (18% fat) diet. In 24-h food-deprived rats, pretreatment with the DA D(2)-receptor antagonist raclopride [100 microg/kg (0.2 micromol/kg) ip] significantly attenuated amylin's (5 microg/kg ip) anorectic effect, whereas raclopride alone had no effect on food intake [i.e., food intakes 1 h after injection were (n = 12): NaCl/NaCl 7.3 +/- 0.5 g; NaCl/amylin 3.9 +/- 0.6; raclopride/NaCl 7.7 +/- 0.7; raclopride/amylin 5.6 +/- 0.7]. Pretreatment with another DA D(2) receptor antagonist, sulpiride [50 mg/kg (154 micromol/kg) ip], similarly reduced amylin's satiety effect, whereas pretreatment with the DA D(1)-receptor antagonist SCH-23390 [10 microg/kg (0.03 micromol/kg) ip] did not influence amylin's effect. SCH-23390, however, completely blocked the anorexia induced by D-amphetamine (0.3 mg/kg ip). These results suggest that, under the present feeding conditions, the dopaminergic system mediates part of amylin's inhibitory effect on feeding in rats when administered intraperitoneally. This seems to involve DA D(2) receptors but not D(1) receptors.

Amyloid↗

PubMed2001

Histamine H1 receptors mediate the anorectic action of the pancreatic hormone amylin.

We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperitoneally injected amylin (5 and 20 microg/kg), the amylin agonist salmon calcitonin (sCT; 10 microg/kg), leptin (1.3 mg/kg), and cholecystokinin (CCK; 20 microg/kg). The experiments were performed with mice lacking functional H1 receptors (H1Rko) and wild-type (WT) controls. The mice were also injected with the H3 antagonist thioperamide (20 mg/kg), which reduces feeding by enhancing the release of endogenous histamine through presynaptic H3 receptors. The feeding-suppressive effect of thioperamide was abolished in H1Rko mice. The anorectic effects of amylin and sCT were significantly reduced in 12-h food-deprived H1Rko mice compared with WT mice [1-h food intake: WT-NaCl 0.51 +/- 0.05 g vs. WT-amylin (5 microg/kg) 0.30 +/- 0.06 g (P < 0.01); H1Rko-NaCl 0.45 +/- 0.05 g vs. H1Rko-amylin 0.40 +/- 0.04 g; WT-NaCl 0.40 +/- 0.09 g vs. WT-sCT (10 microg/kg) 0.14 +/- 0.10 g (P < 0.05); H1Rko-NaCl 0.44 +/- 0.08 g vs. H1Rko-sCT 0.50 +/- 0.06 g]. The anorectic effect of leptin was absent in ad libitum-fed H1Rko mice, whereas CCK equally reduced feeding in WT and H1Rko animals. This suggests that the histaminergic system is involved in mediating the anorectic effects of peripheral amylin and sCT via histamine H1 receptors. The same applies to leptin but not to CCK. H1Rko mice showed significantly increased body weight gain compared with WT mice, supporting the role of endogenous histamine in the regulation of feeding and body weight.

Amyloid↗

PubMed2001

Physiological effect of circulating glucagon on the hepatic membrane potential.

The pancreatic hormone glucagon hyperpolarizes the liver cell membrane under various conditions. Here we investigated the physiological relevance of this effect by testing the influence of infusions of glucagon antiserum on the liver cell membrane potential in vivo. Intracellular microelectrode recordings of liver cells (up to 60/rat over 2 h) were done in anesthetized male rats. Livers were fixed in place, and recordings were done 10-30 min after intraperitoneal injections of glucagon or hepatic portal vein infusions of glucagon or specific polyclonal glucagon antibodies raised in rabbits. The isotonic lactose vehicle was used as a control for glucagon, and equal amounts of nonimmunized rabbit IgG were used as a control for glucagon antibodies. Intraperitoneal glucagon (400 microg/kg) hyperpolarized the liver cell membrane up to 12 mV, and intraportal glucagon (10 or 60 microg/kg) dose dependently hyperpolarized the liver cell membrane by 3-7 mV. Intraportal infusion of glucagon antiserum (in vitro binding capacity of 4 ng glucagon/rat) significantly depolarized the liver cell membrane by approximately 2.5 mV. The effects of both glucagon and glucagon antiserum reversed after 60-90 min. We conclude that glucagon is a physiologically important modulator of the liver cell membrane potential.

Animals↗

PubMed2001

Inhibition of central amylin signaling increases food intake and body adiposity in rats.

Amylin is a 37-amino acid peptide hormone that is co-secreted with insulin by pancreatic beta cells in response to feeding. We recently reported that amylin potently reduces food intake, body weight, and adiposity when delivered into the 3rd cerebral ventricle (i3vt) of rats. We have now infused i3vt a specific antagonist (AC187) to ascertain the physiological relevance of central amylin in the control of energy balance. After establishing the ability of i3vt AC187 to block the anorexic effect of i3vt amylin, we performed an experiment to examine the impact of acute inhibition of central amylin signaling on feeding. Separate groups (n = 7/group) of ad lib-fed male Long Evans rats were given one bolus i3vt infusion of synthetic cerebrospinal fluid vehicle (CSF) or AC187 (250 or 1000 pmol). Acute infusion of AC187 tended to increase 1-h food intake and significantly elevated 4-h intake. Both the 250 and 1000 pmol doses produced significant increases as compared to CSF. In another experiment designed to tonically inhibit central amylin signaling over an extended period, two other groups of rats (n = 6/group) received continuous i3vt infusion of CSF or 100 pmol/h AC187 over 14 days via implantable osmotic pumps. Rats receiving AC187 ate significantly more food over the 14-day infusion period relative to controls (CSF = 322 +/- 6 g, AC187 = 360 +/- 12 g). Although body weight was not significantly affected, body fat was increased by about 30% in the AC187 rats, with no difference in lean tissue between the groups. Additionally, although fasting plasma glucose did not differ between the CSF and AC187 groups after 14 days of infusion, plasma insulin was significantly elevated in the AC187 rats. In summary, the present results document significant increases of food intake and body adiposity resulting from inhibition of central amylin signaling. They are consistent with our hypothesis that CNS actions of endogenous amylin contribute to the long-term regulation of energy balance.

Adipose Tissue↗

PubMed2000

Attenuation of the anorectic effects of cholecystokinin and bombesin by the specific amylin antagonist AC 253.

Previous studies provided evidence for an interaction between the satiety effects of cholecystokinin (CCK), bombesin (BBS), and amylin. Amylin released in response to CCK (or BBS) was supposed to mediate part of CCK's (or BBS's) anorectic effect since the amylin and calcitonin gene-related peptide (CGRP) antagonist CGRP 8-37 attenuated their anorectic action. Due to the low specificity of CGRP 8-37 for amylin vs. CGRP binding sites, the aim of the present study was to test whether the specific amylin antagonist AC 253 also influenced the anorectic effects of CCK and BBS. Injections took place at dark onset in 24-h food-deprived rats. At a dose that attenuated the anorectic effect of amylin (5 microg/kg), the amylin antagonist AC 253 (500 microg/kg) significantly attenuated the anorectic effects of CCK and BBS (0.5 microg/kg). It can therefore be concluded that amylin, rather than CGRP, mediates part of the anorectic effects of CCK and BBS.

Amyloid↗

PubMed2000

Transient hypophagia in rats switched from high-fat diets with different fatty-acid pattern to a high-carbohydrate diet.

The present study investigates the mechanisms underlying the transient hypophagia occurring when rats adapted to high-fat, carbohydrate-free diets are switched to high-carbohydrate, low-fat diets. The hypophagia after the high-fat, carbohydrate-free to high-carbohydrate, low-fat diet shift seems to depend on the amount of carbohydrate in the diet, since an attenuation of hypophagia was observed when high-fat, carbohydrate-free-adapted rats were switched to a medium-carbohydrate, medium-fat diet. A role of glucose intolerance in the hypophagia is supported by the attenuation of carbohydrate anorexia in rats adapted to a high-fat diet containing n -3 polyunsaturated fatty acids from fish oil (60% of fat as fish oil), which has been shown to improve glucose tolerance in rats. Furthermore, the increased plasma glucose concentration in the high-fat, carbohydrate-free diet to high-carbohydrate, low-fat shifted rats despite the suppression in food intake also suggests an involvement of glucose intolerance in the hypophagia. The failure of the inhibitor of hepatic-fatty-acid oxidation mercaptoacetate (400 micromol/kg, i.p.) to counteract carbohydrate anorexia in the HF-adapted rats argues against an involvement of fatty-acids oxidation in the inhibition of eating after high-fat, carbohydrate-free to high-carbohydrate, low-fat diet shift. This is also supported by the failure to demonstrate a relationship between plasma beta-hydroxybutyrate and the severity of the hypophagia. A role of leptin in the hypophagia seems unlikely, since plasma leptin after diet shift was unchanged. Ingestion of the high-carbohydrate, low-fat diet also produced an aversion towards this diet in high-fat, carbohydrate-free-adapted rats. It is concluded that the transient hypophagia induced by switching rats from a high-fat to a high-carbohydrate diet is not related to fatty acid oxidation but to transiently impaired carbohydrate utilization.

Analysis of Variance↗

PubMed2000

Amylin receptors mediate the anorectic action of salmon calcitonin (sCT).

The teleost salmon calcitonin (sCT), but not mammalian CT, shows similar biologic actions in the skeletal muscle as amylin and calcitonin gene-related peptide (CGRP). The peptides have also been shown to reduce food intake in rams. Because sCT, but not amylin, binds irreversibly to amylin binding sites, the aim of the present study was to compare the anorectic potency of both peptides. To determine whether sCT reduces food intake through interaction with amylin binding sites, we also tested whether appropriate antagonists (CORP 8-37, AC 187) attenuate the anorectic effect of sCT. Finally, we wanted to know whether rat calcitonin (rCT) and sCT reduce food intake to the same extent. Peptides were injected intraperitoneally at dark onset in 24 h food-deprived rats. At doses of 5 or 0.5 microg/kg, the anorectic effect of sCT was more potent and lasted much longer (e.g. 5 microg/kg: sCT > 10 h; amylin approx. 2 h) than that of amylin. Both CORP 8-37 and AC 187 (10 microg/kg) markedly reduced the anorectic action of sCT (0.5 microg/kg). In contrast to sCT, rCT (0.5 microg/kg) had no effect on food intake. It is concluded that sCT s anorectic effect is partly mediated by amylin receptors. Irreversible binding of sCT to amylin receptors may lead to a stronger and prolonged effect in comparison to amylin due to a sustained activation of the binding sites. Similar to other actions of CTs, the anorectic potency of sCT in rats was higher than that of mammalian (rat) CT. This agrees with binding profiles of amylin, sCT, and rCT at amylin binding sites as observed in in vitro studies.

Amyloid↗

PubMed2000

Amylin and insulin interact to reduce food intake in rats.

We investigated the hypothesis that amylin and insulin, hormones co-secreted by pancreatic B-cells in response to a nutrient stimulus, interact to reduce food intake. A paradigm was employed that assessed food intake in adult male rats after bolus intravenous (i.v.) infusion at dark onset. In one experiment, rats received saline or amylin (0.1, 0.5 or 1.0 nmol). All amylin doses significantly suppressed 1 h intake, and although significant decreases in cumulative intake persisted for 2 h after 0.5 and 1.0 nmol, a significant increase of food intake actually occurred relative to saline during the interval from 1 to 2 h post-infusion. In another experiment, rats received saline, 0.25 nmol amylin, 10 mU insulin, or the combination of amylin plus insulin. Neither amylin nor insulin alone significantly changed cumulative food intake at any time point as compared to saline. However, the combination significantly reduced intake relative not only to saline but also to amylin and insulin alone after 1, 2, and 4 hours. These data are consistent with the hypothesis that endogenous amylin and insulin interact to reduce food intake and, ultimately, body weight.

Amyloid↗

PubMed2000

Amylin: a novel action in the brain to reduce body weight.

Amylin is a 37-amino acid peptide hormone that is co-secreted with insulin by pancreatic B cells in response to a nutrient stimulus (e.g., during meals). To test the hypothesis that amylin acts within the brain to reduce long-term food intake and body weight, we examined the effects of acute and chronic 3rd-ventricular (i3vt) infusion of low doses of amylin on food intake and body weight in rats. In one experiment, separate groups of ad lib-fed male Long Evans rats were given one i3vt infusion (3 microl over 30 s) of synthetic cerebrospinal fluid vehicle or 1 to 100 pmol amylin, and food intake and body weight were monitored for 7 days. Amylin potently and dose-dependently reduced 1-h food intake, with all doses producing significant reductions. The largest dose (100 pmol) significantly reduced 24-h intake by over 30%. The effect was persistent in that both 7-day cumulative food intake and body weight change were significantly decreased over the 7 days following a single injection of 100 pmol of amylin. Other groups of rats received continuous i3vt infusion (0.5 microl/h volume) of saline or 2.0 pmol/h amylin via osmotic minipumps over 10 days. Food intake over the 10-day infusion was significantly suppressed in amylin-treated rats as compared to that of controls. Consequently, by the 4th day of infusion, amylin rats weighed significantly less than baseline relative to saline controls, and this difference persisted throughout the remainder of the infusion period. At sacrifice (Day 10), the percent of body weight from retroperitoneal fat depots was significantly lower in the amylin-treated rats, indicative of a reduction of total body adiposity. In summary, the results support the hypothesis that amylin acts as a signal to the brain contributing to the maintenance of long-term energy balance.

Amyloid↗