Biomedical subjects

Wolfgang Langhans

Publications and source records attributed to Wolfgang Langhans.

At least 19 recordsLinked to original sources

PubMed2006

Beta-adrenergic-mediated inhibition of feeding by mercaptoacetate in food-deprived rats.

This study investigated the effect of intraperitoneal (IP) injections of the fatty acid oxidation (FAO) inhibitor mercaptoacetate (MA, 45.6 mg/kg) on feeding in food-deprived rats. As previously, MA significantly stimulated feeding in ad libitum-fed rats. MA, however, reduced feeding in 18 and 36 h-fasted rats despite apparently antagonizing the fasting-induced increase in hepatic FAO. To test whether this anorectic effect involves beta-adrenergic stimulation, 36 h-fasted rats were IP injected with the nonspecific beta-adrenergic receptor antagonist propranolol (PROP, 0.5 mg/kg) just before MA injection. PROP attenuated MA's feeding-inhibitory effect, suggesting that MA anorexia is at least partially mediated by beta-adrenergic stimulation. Finally, we evaluated the role of subdiaphragmatic vagal afferent fibers in MA's feeding-inhibitory effect by testing the ability of MA to inhibit food intake in fasted rats after subdiaphragmatic vagal deafferentation (SDA). MA inhibited feeding similarly in SDA rats and sham-operated rats. These data demonstrate that subdiaphragmatic vagal afferents are not necessary for the feeding-inhibitory effect of peripheral MA. These results suggest that the FAO inhibitor MA elicits a feeding-inhibitory effect in fasted rats that is mediated by a different mechanism than its feeding-stimulatory effect.

Adrenergic beta-Antagonists↗

PubMed2006

Vagal afferents mediate the feeding response to mercaptoacetate but not to the beta (3) adrenergic receptor agonist CL 316,243.

To evaluate the role of subdiaphragmatic vagal afferents in the anorectic response to peripheral administration of the highly selective beta(3)-adrenergic receptor agonist CL 316,243 (CL), we tested the ability of intraperitoneal (IP) injections of CL to inhibit feeding in rats with subdiaphragmatic vagal deafferentation (SDA, n=13) or sham surgeries (SHAM, n=13). Doses of 10, 100 and 1000 ng/kg CL significantly reduced feeding by statistically similar amounts in SHAM and SDA rats. One hour after IP injection, each dose of CL also significantly increased plasma concentrations of free fatty acids and beta-hydroxybutyrate, an indicator of hepatic fatty acid oxidation (FAO), whereas 6h after injection only the two highest CL doses increased plasma beta-hydroxybutyrate. In contrast, peripheral administration of the FAO inhibitor mercaptoacetate (MA, 45.6 mg/kg IP) stimulated feeding in SHAM but not in SDA rats, extending previous data suggesting a necessary role of vagal afferents in the feeding-stimulatory effect of FAO inhibition. We conclude that subdiaphragmatic vagal afferents are essential for the feeding-stimulatory action of MA but not for the anorectic action of peripheral CL and that CL-induced increase in hepatic FAO is not essential for its feeding-inhibitory effect.

3-Hydroxybutyric Acid↗

PubMed2006

Gut vagal afferents are not necessary for the eating-stimulatory effect of intraperitoneally injected ghrelin in the rat.

Ghrelin is unique among gut peptides in that its plasma level increases during fasts and its administration stimulates eating. Although ghrelin physiology has been intensively studied, whether its eating-stimulatory effect arises from endocrine-neural signal transduction at peripheral or central sites remains unresolved. To address this issue, we tested the effects of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method available, on ghrelin-induced eating. SDA was verified with a cholecystokinin satiation test, retrograde labeling of vagal motor neurons in the dorsal motor nucleus of the vagus with fluorogold, and anterograde labeling of vagal afferents in the nucleus tractus solitarius with wheat germ agglutinin-horseradish peroxidase. Intraperitoneal injections of 10-40 microg/kg ghrelin stimulated eating as robustly in rats with verified complete SDA as in sham-operated controls. Ghrelin also stimulated eating in rats with total subdiaphragmatic vagotomies. We also recorded the electrophysiological responses of gastric load-sensitive vagal afferent neurons to intravenous ghrelin. Ghrelin (10 nmol) phasically (0-30 s) increased activity in two of seven gastric load-sensitive fibers in the absence of gastric loads and tonically (5-30 min) increased activity in only one fiber. Ghrelin did not affect any of the eight fibers tested in the presence of 1-3 ml gastric loads. We conclude that although phasic increases in plasma ghrelin may affect the activity of a fraction of gastric load-sensitive vagal afferents, the acute eating-stimulatory effect of intraperitoneal ghrelin does not require vagal afferent signaling.

Afferent Pathways↗

PubMed2006

Effects of obestatin on energy balance and growth hormone secretion in rodents.

Ghrelin stimulates food intake and adiposity and thereby increases body weight (BW) in rodents after central as well as peripheral administration. Recently, it was discovered that the gene precursor of ghrelin encoded another secreted and bioactive peptide named obestatin. First reports appeared to demonstrate that this peptide requires an amidation for its biological activity and acts through the orphan receptor, GPR-39. Obestatin was shown to have actions opposite to ghrelin on food intake, BW, and gastric emptying. In the present study, we failed to observe any effect of obestatin on food intake, BW, body composition, energy expenditure, locomotor activity, respiratory quotient, or hypothalamic neuropeptides involved in energy balance regulation. In agreement with the first report, we were unable to find any effect of obestatin on GH secretion in vivo. Moreover, we were unable to find mRNA expression of GPR-39, the putative obestatin receptor, in the hypothalamus of rats. Therefore, the results presented here do not support a role of the obestatin/GPR-39 system in the regulation of energy balance.

Animals↗

PubMed2006

Effect of sainfoin (Onobrychis viciifolia) silage and hay on established populations of Haemonchus contortus and Cooperia curticei in lambs.

The objective of the study was to examine the effect of dried and ensiled sainfoin (Onobrychis viciifolia) on established populations of Haemonchus contortus (abomasum) and Cooperia curticei (small intestine) in lambs under controlled conditions. Twenty-four parasite naïve lambs were inoculated with a single dose of infective larvae of these parasites 28 days prior to the start of the feeding experiment. Twenty-four days post-infection, 4 days prior to the start of the feeding experiment, animals were allocated to four groups according to egg excretion, live weight and sex. Groups A and B received sainfoin hay and control hay, respectively, for 16 days. Groups C and D were fed on sainfoin silage or control silage for the same period. Feeds were offered ad libitum and on the basis of daily refusals were supplemented with concentrate in order to make them isoproteic and isoenergetic. Individual faecal egg counts on a dry matter basis (FECDM) were performed every 3-4 days and faecal cultures and packed cell volume (PCV) measurements were done weekly. After 16 days of experimental feeding, all animals were slaughtered and adult worm populations were determined. The consumption of conserved sainfoin was associated with a reduction of adult H. contortus (47% in the case of hay, P<0.05; 49% in the case of silage, P=0.075) but had little effect on adult C. curticei. Compared to the controls, H. contortus specific FECDM was reduced by 58% (P<0.01) in the sainfoin hay group and by 48% (P=0.075) in the sainfoin silage group. For both sainfoin feeds FECDM specific to C. curticei were significantly decreased when compared to the control feeds (hay 81% and silage 74%, both tests P<0.001). Our data suggest that different mechanisms were responsible for the reduction in FECDM in response to feeding tanniferous fodder. For H. contortus, the decrease seemed to be due to a nematocidal effect towards adult H. contortus. In contrast for C. curticei, the reduction in FECDM appeared to be a result of a reduced per capita fecundity. For both, hay and silage, an antiparasitic effect could be shown, offering promising perspectives for the use of conserved tanniferous fodder as a complementary control approach against GIN.

Abomasum↗

PubMed2006

Hepatic-portal oleic acid inhibits feeding more potently than hepatic-portal caprylic acid in rats.

In several human and animal studies, medium-chain triglycerides decreased food intake more than did long-chain triglycerides. It is possible that faster uptake and metabolism of medium-chain fatty acids in the liver is responsible for this difference. To test this hypothesis we compared the feeding effects of hepatic portal vein (HPV) infusion of the medium-chain fatty acid caprylic acid (CA) with those of the long-chain fatty acid oleic acid (OA). Contrary to our expectation, six-h HPV infusion of 14 microg/min (50 nmol/min) OA robustly inhibited feeding, whereas infusion of 22 or 220 microg/min (150 and 1500 nmol/min) CA failed to have any effect on feeding. Only a much larger dose of CA, 1100 microg/min (7500 nmol/min) inhibited feeding similarly to 14 microg/min OA. The increased feeding-inhibitory potency of OA did not appear to be due to differences in stimulation of hepatic fatty acid oxidation because equimolar (50 nmol/min) doses of OA (14 microg/min) and CA (7 microg/min) did not differentially affect post-infusion levels of beta-hydroxybutyrate. Stress, inflammation, acute hepatotoxicity or oxidative stress also do not appear to account for the increased feeding-inhibitory potency of HPV OA because plasma concentrations of the stress hormones corticosterone and epinephrine, the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, the liver enzymes gamma-glutamyl transferase and alanine aminotransferase and as well as hepatic levels of malondialdehyde and glutathione were all similar after HPV infusion of saline or of 50 nmol/min OA or CA.

Animals↗

PubMed2006

Pancreatic signals controlling food intake; insulin, glucagon and amylin.

The control of food intake and body weight by the brain relies upon the detection and integration of signals reflecting energy stores and fluxes, and their interaction with many different inputs related to food palatability and gastrointestinal handling as well as social, emotional, circadian, habitual and other situational factors. This review focuses upon the role of hormones secreted by the endocrine pancreas: hormones, which individually and collectively influence food intake, with an emphasis upon insulin, glucagon and amylin. Insulin and amylin are co-secreted by B-cells and provide a signal that reflects both circulating energy in the form of glucose and stored energy in the form of visceral adipose tissue. Insulin acts directly at the liver to suppress the synthesis and secretion of glucose, and some plasma insulin is transported into the brain and especially the mediobasal hypothalamus where it elicits a net catabolic response, particularly reduced food intake and loss of body weight. Amylin reduces meal size by stimulating neurons in the hindbrain, and there is evidence that amylin additionally functions as an adiposity signal controlling body weight as well as meal size. Glucagon is secreted from A-cells and increases glucose secretion from the liver. Glucagon acts in the liver to reduce meal size, the signal being relayed to the brain via the vagus nerves. To summarize, hormones of the endocrine pancreas are collectively at the crossroads of many aspects of energy homeostasis. Glucagon and amylin act in the short term to reduce meal size, and insulin sensitizes the brain to short-term meal-generated satiety signals; and insulin and perhaps amylin as well act over longer intervals to modulate the amount of fat maintained and defended by the brain. Hormones of the endocrine pancreas interact with receptors at many points along the gut-brain axis, from the liver to the sensory vagus nerve to the hindbrain to the hypothalamus; and their signals are conveyed both neurally and humorally. Finally, their actions include gastrointestinal and metabolic as well as behavioural effects.

Amyloid↗

PubMed2006

Mercaptoacetate fails to block the feeding-inhibitory effect of the beta3-adrenergic receptor agonist CGP 12177A.

Peripherally administered beta3-adrenergic receptor (beta3-AR) agonists stimulate lipolysis and inhibit food intake. To test the hypothesis that this inhibition of feeding is due to a substrate-driven increase in hepatic fatty acid oxidation (FAO), we assessed the ability of the FAO inhibitor mercaptoacetate (MA) to reverse the feeding-inhibitory effect of the beta3-AR agonist CGP 12177A (CGP). Adult male Sprague-Dawley rats received intraperitoneal injections of 1 mg/kg CGP, of 45.6 mg/kg MA, or of both drugs, and the effects on food intake, plasma free fatty acids (FFA), and plasma beta-hydroxybutyrate (BHB), an indicator for hepatic FAO, were assessed. Control rats received saline injections. CGP significantly reduced food intake after 0.5 and 6 h and increased plasma FFA and BHB at 0.5 h, suggesting increased lipolysis and hepatic FAO. MA completely reversed the increase in plasma BHB and thus appeared to effectively abolish CGP's effect on hepatic FAO, but MA failed to affect CGP's feeding-inhibitory action. These findings do not support the hypothesis that the beta3-AR agonist CGP inhibits feeding by enhancing hepatic FAO or ketogenesis. Although the beta3-AR agonist CGP reduced saccharin intake in a one-bottle condition taste aversion test, it seems unlikely that the hypophagic effect of CGP is elicited by malaise.

3-Hydroxybutyric Acid↗

PubMed2006

Beneficial and deleterious effects of hydroxycitrate in rats fed a high-fructose diet.

OBJECTIVE: The present study assessed whether long-term supplementation of a high-fructose diet with hydroxycitrate (HCA), an inhibitor of de novo lipogenesis that is widely used as a non-prescription dietary aid, decreases food intake, visceral fat accumulation, hypertriglyceridemia, and hyperinsulinemia in rats. METHODS: We examined the effects of HCA (1.8% of diet) on food intake, body weight gain, visceral fat accumulation, hypertriglyceridemia, and hyperinsulinemia in rats during a 4-wk period of ad libitum access to a 50% fructose diet after a 3-wk period of food restriction in which they lost about 20% of their body weight. RESULTS: HCA decreased food intake and weight gain throughout the test and reduced visceral fat accumulation compared with control rats fed ad libitum (CON). Rats that were pair-fed (PF) to the HCA rats showed similar decreases in weight gain and visceral fat. HCA did not ameliorate the hypertriglyceridemia induced by high-fructose feeding. HCA improved insulin sensitivity on day 10 in comparison with CON rats, but by day 27 insulin levels were similarly higher and liver glycogen levels were similarly lower in HCA and CON rats in comparison with PF rats. Liver lipid content was elevated in HCA rats compared with CON and PF rats. CONCLUSION: These findings indicate that, although HCA attenuates body weight gain and visceral fat accumulation by reducing food intake under these conditions, it has no lasting beneficial effects on hypertriglyceridemia and hyperinsulinemia and leads to the accumulation of liver lipids.

Animals↗

PubMed2006

Increased infarct size and lack of hyperphagic response after focal cerebral ischemia in peroxisome proliferator-activated receptor beta-deficient mice.

Peroxisome proliferator-activated receptors (PPARs) are involved in energy expenditure, regulation of inflammatory processes, and cellular protection in peripheral tissues. Among the different types of PPARs, PPARbeta is the only one to be widely expressed in cortical neurons. Using PPARbeta knockout (KO) mice, we report here a detailed investigation of the role of PPARbeta in cerebral ischemic damage, associated inflammatory and antioxidant processes as well as food intake regulation after middle cerebral artery occlusion (MCAO). The PPARbeta KO mice had a two-fold increase in infarct size compared with wild-type (WT) mice. Brain oxidative stress was dramatically enhanced in these KO mice, as documented by an increased content of malondialdehyde, decreased levels of glutathione and manganese superoxide dismutase, and no induction of uncoupling protein 2 (UCP2) mRNA. Unlike WT mice, PPARbeta KO mice showed a marked increase of prooxidant interferon-gamma but no induction of nerve growth factor and tumor necrosis factor alpha after MCAO. In WT mice, MCAO resulted in inflammation-specific transient hyperphagia from day 3 to day 5 after ischemia, which was associated with an increase in neuropeptide Y (NPY) mRNA. This hyperphagic phase and NPY mRNA induction were not observed in PPARbeta KO mice. Furthermore, our study also suggests for the first time that UCP2 is involved in MCAO food intake response. These data indicate that PPARbeta plays an important role in integrating and regulating central inflammation, antioxidant mechanisms, and food intake after MCAO, and suggest that the use of PPARbeta agonists may be of interest for the prevention of central ischemic damage.

Animals↗

PubMed2006

Effect of concurrent vitamin A and iodine deficiencies on the thyroid-pituitary axis in rats.

OBJECTIVE: Deficiencies of vitamin A and iodine are common in many developing countries. Vitamin A deficiency (VAD) may adversely affect thyroid metabolism. The study aim was to investigate the effects of concurrent vitamin A and iodine deficiencies on the thyroid-pituitary axis in rats. DESIGN: Weanling rats (n = 56) were fed diets deficient in vitamin A (VAD group), iodine (ID group), vitamin A and iodine (VAD + ID group), or sufficient in both vitamin A and iodine (control) for 30 days in a pair-fed design. Serum retinol (SR), thyroid hormones (FT(4), TT(4), FT(3), and TT(3)), serum thyrotropin (TSH), pituitary TSHbeta mRNA expression levels, and thyroid weights were determined at the end of the depletion period. MAIN OUTCOME: Compared to the control and ID groups, SR concentrations were about 35% lower in the VAD and VAD + ID groups (p < 0.001), indicating moderate VA deficiency. Comparing the VAD and control groups, there were no significant differences in TSH, TSHbeta mRNA, thyroid weight, or thyroid hormone levels. Compared to the control group, serum TSH, TSHbeta mRNA, and thyroid weight were higher (p < 0.05), and FT4 and TT4 were lower (p < 0.001), in the VAD + ID and ID groups. Compared to the ID group, TSH, TSHbeta mRNA, and thyroid weight were higher (p < 0.01) and FT(4) and TT(4) were lower (p < 0.001) in the VAD + ID group. There were no significant differences in TT3 or FT3 concentrations among groups. CONCLUSION: Moderate VAD alone has no measurable effect on the pituitary-thyroid axis. Concurrent ID and VAD produce more severe primary hypothyroidism than ID alone.

Animals↗

PubMed2005

Caprylic acid infusion acts in the liver to decrease food intake in rats.

Hepatic portal vein (HPV) infusion of the medium chain fatty acid caprylic acid (CA; 2.3 mg/min, 40 microl/min) for 90 min beginning at dark onset in 18-h food-deprived male rats reduced the size of the first nocturnal meal about 40% (P < 0.01) and reduced 24-h food intake by about 15% (P < 0.001). Identical infusions into the vena cava affected neither initial meal size nor food intake. HPV CA infusion attenuated the postprandial decreases in plasma free fatty acids (P < 0.01) and beta-hydroxybutyrate (P < 0.01). HPV CA infusions did not significantly reduce nocturnal saccharine intake in a two-bottle conditioned taste aversion test, and there was no association between the saccharine intake on the test day and the feeding-inhibitory effect of CA on the conditioning day. HPV CA infusion did not affect plasma concentrations of corticosterone or of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha. HPV CA infusion did not increase plasma concentration of the liver enzyme alanine aminotransferase, but did increase plasma concentration of gamma-glutamyl transferase, although not into the pathophysiological range. These data indicate that CA acts in the liver to produce a signal that inhibits feeding and that this inhibitory effect may be related to increases in hepatic fatty acid oxidation rather than be the result of aversion or toxicity.

3-Hydroxybutyric Acid↗

PubMed2005

Effect of intraperitoneal CCK-8 on food intake and brain orexin-A after 48 h of fasting in the rat.

We investigated the interactions of the peripheral satiety peptide cholecystokinin and the brain orexin-A system in the control of food intake. The effect of an intraperitoneal (i.p.) injection of sulfated cholecystokinin octapeptide (in this article called CCK) (5 microg/kg, 4.4 nmol/kg) or of phosphate-buffered saline (PBS, vehicle control) on 48 h fasting-induced feeding and on orexin-A peptide content was analyzed in diverse brain regions innervated by orexin neurons and involved in the control of food intake. Administration of CCK after a 48 h fast reduced fasting-induced hyperphagia (P<0.05). I.p. CCK increased the orexin-A content in the posterior brainstem of 48 h fasted rats by 35% (P<0.05). Fed animals receiving CCK had 48% higher orexin-A levels in the posterior brainstem than fasted rats (P<0.05). In the lateral hypothalamus, fasting decreased orexin-A levels by 50% as compared to fed rats (P<0.05). In the septal nuclei, the combination of fasting and CCK administration reduced orexin-A contents compared to fed PBS and CCK animals by 13% and 17%, respectively (P<0.05). These results suggest a convergence of pathways activated by peripheral CCK and by fasting on the level of orexin-A released in the posterior brainstem and provide evidence for a novel interaction between peripheral satiety signaling and a brain orexigen in the control of food intake.

Animals↗

PubMed2005

CPT1alpha over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells.

To test the cellular response to an increased fatty acid oxidation, we generated a vector for an inducible expression of the rate-limiting enzyme carnitine palmitoyl-transferase 1alpha (CPT1alpha). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1alpha transgene in the tet-on vector was activated with doxycycline. Fatty acid oxidation was measured by determining the conversion of supplemented, synthetic cis-10-heptadecenoic acid (C17:1n-7) to C15:ln-7. CPT1alpha over-expression increased mitochondrial long-chain fatty acid oxidation about 6-fold. Addition of palmitic acid (PA) decreased viability of CPT1alpha over-expressing cells in a concentration-dependent manner. Both, PA and CPT1alpha over-expression increased cell death. Interestingly, PA reduced total cell number only in cells over-expressing CPT1alpha, suggesting an effect on cell proliferation that requires PA translocation across the mitochondrial inner membrane. This inducible expression system should be well suited to study the roles of CPT1 and fatty acid oxidation in lipotoxicity and metabolism in vivo.

Carnitine O-Palmitoyltransferase↗

PubMed2005

Stress-induced changes in human salivary alpha-amylase activity -- associations with adrenergic activity.

The salivary enzyme alpha-amylase has been proposed to indicate stress-reactive bodily changes. A previous study by the authors revealed marked increases in salivary alpha-amylase following psychosocial stress, indicating a stress-dependent activation of salivary alpha-amylase. Salivary alpha-amylase has been suggested to reflect catecholaminergic reactivity. Our aim was to assess/evaluate a possible relationship between salivary alpha-amylase and adrenergic parameters, i.e. catecholamines, as well as other stress markers. Using an intra-individual repeated measures design, 30 healthy young men underwent the Trier Social Stress Test (TSST), which consists of a mental arithmetic task and free speech in front of an audience and a control condition in randomized order. Salivary alpha-amylase and salivary cortisol as well as plasma catecholamines and cardiovascular activity were repeatedly measured before, during, and after both conditions. Significant differences were found between the stress and the rest condition in salivary alpha-amylase, salivary cortisol, plasma catecholamines, and cardiovascular parameters (heart rate, LF, HF, LF/HF). However, general alpha-amylase responses (area under the curve) were not associated with general responses in catecholamines and cortisol in the stress condition (r smaller than 0.25 for all analyses). Analysis of cardiovascular parameters indicates a positive relationship between amylase and sympathetic tone (LF/HF) during stress. Salivary alpha-amylase is sensitive to psychosocial stress. Since it does not seem to be closely related to other biological stress markers such as catecholamines and cortisol, salivary alpha-amylase may be a useful additional parameter for the measurement of stress.

Adult↗

PubMed2005

Subdiaphragmatic vagal deafferentation affects body weight gain and glucose metabolism in obese male Zucker (fa/fa) rats.

We investigated the effect of subdiaphragmatic vagal deafferentation (SDA) on food intake, body weight gain, and metabolism in obese (fa/fa) and lean (Fa/?) Zucker rats. Before and after recovery from surgery, food intake and body weight gain were recorded, and plasma glucose and insulin were measured in tail-prick blood samples. After implantation of a jugular vein catheter, an intravenous glucose tolerance test (IVGTT) was performed, followed by minimal modeling to estimate the insulin sensitivity index. Food intake relative to metabolic body weight (g/kg(0.75)) and daily body weight gain after surgery were lower (P < 0.05) in SDA than in sham obese but not lean rats. Before surgery, plasma glucose and insulin concentrations were lower (P < 0.05) in lean than in obese rats but did not differ between surgical groups within both genotypes. Four weeks after surgery, plasma glucose and insulin were still similar in SDA and sham lean rats but lower (P < 0.05) in SDA than in sham obese rats. IVGTT revealed a downward shift of the plasma insulin profile by SDA in obese but not lean rats, whereas the plasma glucose profile was unaffected. SDA decreased (P < 0.05) area under the curve for insulin but not glucose in obese rats. The insulin sensitivity index was higher in lean than in obese rats but was not affected by SDA in both genotypes. These results suggest that elimination of vagal afferent signals from the upper gut reduces food intake and body weight gain without affecting the insulin sensitivity index measured by minimal modeling in obese Zucker rats.

Animals↗

PubMed2005

Enterostatin decreases postprandial pancreatic UCP2 mRNA levels and increases plasma insulin and amylin.

This study investigated the chronic effect of enterostatin on body weight and some of the associated changes in postprandial metabolism. Rats were adapted to 6 h of food access/day and a choice of low-fat and high-fat (HF) food and then given enterostatin or vehicle by an intraperitoneally implanted minipump delivering 160 nmol enterostatin/h continuously over a 5-day infusion period. Enterostatin resulted in a slight but significant reduction of HF intake and body weight. After the last 6-h food access period, enterostatin-treated animals had lower plasma triglyceride and free fatty acid but higher plasma glucose and lactate levels than control animals. Enterostatin infusion resulted in increased uncoupling protein-2 (UCP2) expression in various tissues, including epididymal fat and liver. UCP2 was reduced in the pancreas of enterostatin-treated animals, and this was associated with increased plasma levels of insulin and amylin. Whether these two hormones are involved in the observed decreased food intake due to enterostatin remains to be determined. As lipid metabolism appeared to be altered by enterostatin, we measured peroxisome proliferator-activated receptor (PPAR) expression in tissues and observed that PPARalpha, -beta, -gamma1, and -gamma2 expression were modified by enterostatin in epididymal fat, pancreas, and liver. This further links altered lipid metabolism with body weight loss. Our data suggest that alterations in UCP2 and PPARgamma2 play a role in the control of insulin and amylin release from the pancreas. This implies that enterostatin changes lipid and carbohydrate metabolic pathways in addition to its effects on food intake and energy expenditure.

Amyloid↗

PubMed2005

Effect of CCK-8 on insulin-induced hyperphagia and hypothalamic orexigenic neuropeptide expression in the rat.

The influence of cholecystokinin octapeptide (CCK-8) on normal and insulin-induced feeding and expression of orexigenic hypothalamic neuropeptides was investigated in male rats. CCK-8, administered during meals (4 microg/kg) or continuously (32 microg/kg over 60 min), blunted the stimulating effect of insulin (50 IU/kg) on feeding by reducing meal size (-60%; P<0.05 or -86%; P<0.0001, respectively). Rats without access to food and injected with IP insulin (50 IU/kg) showed increased hypothalamic mRNA levels of orexin (+30%; P<0.05) and melanin-concentrating hormone (+52%; P<0.05), as compared with ad libitum-fed and saline-injected control rats. Continuous IP infusion of CCK-8 (32 microg/kg) blunted these increases. Our results suggest that both orexin and melanin-concentrating hormone participate in the response to insulin hypoglycemia without food being present; these neurons may be involved in mechanisms related to insulin-induced hyperphagia. Signals triggered by peripheral CCK-8 act to decrease the expression of orexin and melanin-concentrating hormone. This may be associated with a reduction in hyperphagia.

Animals↗