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Biomedical subjects

D A York

Publications and source records attributed to D A York.

At least 55 records · Page 3Linked to original sources
PubMed1997

Chronic ICV enterostatin preferentially reduced fat intake and lowered body weight.

The pancreatic peptide enterostatin will acutely reduce fat intake in rats provided a choice of diets. Chronic ICV infusions of enterostatin suppress the intake of high fat diet. However, the effects of chronic ICV enterostatin on diet choice has not previously been studied. To investigate this, enterostatin (0.5 microgram/h) or artificial cerebrospinal fluid (CSF) was infused for 9 days into the lateral ventricle of rats adapted to a two-choice high-fat (HF) and low-fat (LF) diet regime. Enterostatin reduced intake of HF diet with the maximum depression at day 4, but there was no compensatory increase in LF intake. The body weight of enterostatin-infused rats declined. This was associated with a reduction in fat pad and liver weights compared to the CSF-infused control rats. Serum triglycerides and insulin were decreased and corticosterone was elevated in enterostatin-infused rats. The data show that enterostatin will chronically reduce fat intake and body weight and suggest that enterostatin may attenuate the appetite for fat.

Animals↗
PubMed1997

Enterostatin actions in the amygdala and PVN to suppress feeding in the rat.

The pentapeptide enterostatin (ENT) inhibits feeding after injection into the cerebral ventricles. To localize the central sites of action of ENT, the peptide (0.01 to 3.3 nM) was microinjected into several brain regions and the intake of a high fat diet was measured. The results show that ENT injection in the paraventricular nucleus (PVN) or the amygdala (AMYG) produced a bi-phasic dose related feeding response, low doses of ENT inhibited feeding while higher dose had no effect. The effective dose to inhibit feeding in the AMYG was 10 fold lower than that in the PVN. No changes in food intake were observed after ENT injection into the ventromedial hypothalamus and nucleus tractus solitarius. The data provide further support that there are targets in the CNS for ENT and suggest that central ENT function is site specific.

Adaptation, Physiological↗
PubMed1997

Carbohydrate versus fat intake: differing patterns of macronutrient selection in two inbred mouse strains.

As a first step toward developing a mouse model to characterize genetic factors linked to the preferential intake of dietary carbohydrate or fat, we have identified two mouse strains that exhibit distinctly different patterns of macronutrient selection. Macronutrient selection was evaluated in AKR/J and SWR/J mice, two strains that have been characterized previously for their sensitivity to high-fat dietary obesity. Mice were adapted to a self-selection protocol in which separate carbohydrate, fat, and protein sources were simultaneously available. AKR/J mice ate 30% more calories than the SWR/J mice. Furthermore, strain comparisons revealed a significantly higher proportion of fat intake by the AKR/J mice (69 vs. 28%), and in the SWR/J mice a significantly higher intake of carbohydrate (62 vs. 24%). The mice were then returned to a standard chow diet for 10 wk. These mice subsequently were allowed to self-select from two composite energy diets (carbohydrate and protein, or fat and protein). Once again, AKR/J mice selected a greater proportion of energy from the fat/protein diet (85%) than did the SWR/J strain (32%). These findings suggest a possible relationship between sensitivity to dietary obesity and fat selection.

Animal Nutritional Physiological Phenomena↗
PubMed1997

Chemical lesion of visceral afferents causes transient overconsumption of unfamiliar high-fat diets in rats.

Because it is commonly assumed that the major role of visceral afferents in food intake control is to terminate meals by carrying negative-feedback signals to the brain, we hypothesized that overconsumption should occur in rats with chemically lesioned visceral afferents if they were presented with an unfamiliar diet. Adult male Sprague-Dawley (SD) rats were treated with multiple doses of capsaicin or vehicle as a control. Five weeks later, a series of 3-h feeding tests after 24-h deprivation was carried out, first with chow and then with either a solid (vegetable shortening) or liquid (Ensure) unfamiliar high-fat diet. Both groups consumed similar amounts of their powdered chow maintenance diet, but capsaicin-treated rats consumed at least 50% more of either high-fat diet than vehicle controls (P < 0.01) at the beginning of the first trial. During second and third trials with the now-familiar high-fat diet, intake was no longer significantly different between the two groups, suggesting rapid engagement of redundant control mechanisms. These results support a role of capsaicin-sensitive visceral afferents in providing negative feedback for early meal termination during the ingestion of unfamiliar diets.

Afferent Pathways↗
PubMed1996

Effect of galanin and enterostatin on sympathetic nerve activity to interscapular brown adipose tissue.

The effects of galanin and enterostatin on sympathetic activity have been examined in rats using electrophysiological techniques. Galanin, in doses of 25-300 pmol, and enterostatin, in doses of 0.5-10 nmol, were injected into the third ventricle of anesthetized male Sprague-Dawley rats in 1-microliter volumes. Galanin produced a dose-dependent suppression (ranging between 20 and 80%) of sympathetic firing rate of nerves innervating interscapular brown adipose tissue. In rats fed a chow diet, injection of enterostatin produced only a transient 10% rise in firing rate which returned to baseline within 10-15 min. In contrast, animals fed a high-fat diet showed a dose-dependent increase in firing rate lasting for 60 min. The results of this experiment are consistent with the hypothesis that food intake and sympathetic nervous system activity have a reciprocal relationship. The implications of this relationship are discussed.

Adipose Tissue, Brown↗
PubMed1996

Comparison of Osborne-Mendel and S5B/PL strains of rat: central effects of galanin, NPY, beta-casomorphin and CRH on intake of high-fat and low-fat diets.

The effects of central administration of galanin, neuropeptide Y (NPY), beta-casomorphin(1-7) and corticotropin releasing hormone (CRH) on intake of either a high-fat or low-fat diet have been compared in two strains of rat, the dietary fat-sensitive Osborne-Mendel (OM) rat and the dietary fat-resistant S5B/Pl rat. Injection of galanin (0.1, 0.3 nmoles) into the 3rd cerebral ventricle stimulated the intake of both a high-fat and a low-fat diet in OM rats in a dose dependent manner but the response was significantly smaller in rats fed the low-fat diet. In S5B/Pl rats, galanin had a small stimulatory effect on food intake but only at a high dose (2 nmole). Beta-casomorphin(1-7) (5 nmoles), an opioid-like peptide, increased the intake of the high-fat but not the low-fat diet in OM rats, whereas S5B/Pl rats fed either a high-fat or low-fat diet did not respond to beta-casomorphin(1-7). Both strains showed a similar stimulatory response to NPY (0.1, 0.5 nmoles) on the intake of the high-fat or low-fat diet, but the magnitude of the response was attenuated in S5B/Pl rats. In contrast, the anorectic effects of CRH (0.26 nmoles) on food deprived animals was similar in both strains for both diets. We speculate that the regulatory system controlling the intake of fat activated by galanin and beta-casomorphin(1-7) may be defective in S5B/Pl rats.

Animals↗
PubMed1996

Abnormal regulation of hepatic glucocorticoid receptor mRNA and receptor protein distribution in the obese Zucker rat.

This study examines the cellular distribution of glucocorticoid receptor (GR) protein and transcriptional activity of the GR gene in the liver of Zucker obese (fa/fa) rats. Immunoabsorption and Western blotting showed an increase in nuclear GR protein level but a decrease in cytosolic GR levels in the liver of 5-week old male obese rats (fa/fa) compared to their lean littermates (Fa/-). These changes were confirmed by receptor-ligand binding assays with [3H]-dexamethasone which showed a sixfold increase in average obese nuclear GR binding and a twofold reduction in cytosolic GR binding. HSP90, but not HSP70, levels were reduced in hepatic cytosol and increased in hepatic nuclei prepared from obese rats. Using Northern blot analysis of hepatic RNA, we demonstrated a twofold increase in hepatic mRNAs for GR, malic enzyme (ME), tyrosine aminotransferase (TAT), and glyceraldehyde 3-PO4-dehydrogenase in the obese rat. Increased transcription of GR and ME mRNAs in obese nuclei was indicated in nuclear run-on assays. These data suggest that there is increased nuclear localization of GR in the liver of obese rats and suggests that increased transcription of GR gene may contribute to this effect. The described changes may contribute to the abnormal regulation by glucocorticoids of some hepatic genes in the Zucker fa/fa rat.

Animals↗
PubMed1996

Effects of pyruvate and lactate on food intake in rat strains sensitive and resistant to dietary obesity.

We have investigated the effects of peripherally administered pyruvate and lactate on the intake of high fat (HF) and low fat (LF) diets by a strain of rat either sensitive (Osborne-Mendel, OM) or resistant (SSB/Pl) to high fat-induced obesity. Both pyruvate and lactate inhibited the intake of HF and LF diets by OM rats and these effects were blocked by selective hepatic vagotomy. In contrast, in S5B/Pl rats fed an LF diet the responses to pyruvate and lactate were attenuated and were absent in S5B/Pl rats fed the HF diet. These data suggest that OM and S5B/Pl rats differ either in their metabolism of pyruvate and lactate or in their responses to these metabolites.

Animals↗
PubMed1996

Opioid receptor subtype control of galanin-induced feeding.

This study examined the effects of specific antagonists to kappa- and mu-opioid receptors on the feeding induced by injecting galanin into the lateral cerebral ventricle (LCV). Galanin injected into the lateral cerebral ventricle of sated rats stimulated the consumption of high-fat diet when compared to controls injected with saline vehicle. The mu-opioid receptor antagonist, CTOP, completely abolished galanin-induced feeding in sated rats whereas the kappa-opioid receptor antagonist, nor-BNI, had no effect on galanin-induced feeding. Neither CTOP nor nor-BNI alone produced any change in food consumption in sated rats. In fasted rats, on the other hand, nor-BNI significantly decreased consumption of a high-fat diet (> 83%) when compared to animals treated with the saline vehicle, whereas CTOP had no significant effect. These findings suggest that galanin-induced feeding of a high-fat diet is selectively modulated by a pathway involving mu-opioid receptors whereas feeding induced by fasting is dependent on a pathway mediated by kappa-opioid receptors. These data also suggest that galanin does not mediate the feeding response after fasting.

Animals↗
PubMed1996

Effects of dietary preference and galanin administration in the paraventricular or amygdaloid nucleus on diet self-selection.

Microinjection of galanin into the paraventricular nucleus (PVN) of the hypothalamus has been reported to predominantly increase dietary fat consumption during the light or late dark periods. However, there have been no studies of the macronutrient-specific effects of galanin administered into the amygdala (AMY). We used male Sprague-Dawley rats to test the effect of galanin administered into the PVN or central nucleus of the AMY on diet selection using two different protocols: the two-choice composite diet (10% or 55% energy as fat) (Study 1) or the three-choice macronutrient diet (Study 2). In the first study, total food intake was significantly increased 60 min after galanin injection (0.3 nmol) into either the PVN or AMY, but there was no difference in intake between the low- and high-fat diets. In Study 2, using the three-choice macronutrient diet, the feeding stimulation produced by galanin in the PVN also was not diet-dependent. In the AMY, there was a significant effect of diet on the feeding response to galanin, due primarily to the lack of stimulation of protein intake, whereas the intakes of fat and carbohydrate were not significantly different. In summary, there was no difference in the effect of galanin on fat versus carbohydrate intake for either nuclei, whether animals were injected during the light or the late-dark phase. Because rats often display preferences when allowed to choose among individual macronutrient sources, we also examined the relationship between baseline macronutrient preference and the feeding response to galanin in groups of highly fat-preferring and carbohydrate-preferring rats (Study 3). After PVN galanin injection, fat-preferring rats demonstrated significant increases in their consumption of both carbohydrate and fat, whereas carbohydrate-preferring rats responded by eating carbohydrate almost exclusively. There were significant positive associations between baseline macronutrient intake and galanin-induced intake. The results of these studies combined suggest that the effect of galanin on macronutrient selection is not specific for fat and that underlying macronutrient preferences are important in determining the feeding response to galanin.

Amygdala↗
PubMed1996

Lessons from animal models of obesity.

Obesity in animals may result from genetic, dietary, or neuroendocrine perturbations. Study of these models has identified the central systems that regulate food intake and energy expenditure and identified the interdependence of feeding behavior, the autonomic nervous system, and adrenal glucocorticoids in the development of obesity. The animal models of obesity have been influential in showing that adipose tissue is an important secretory tissue. The recent identification of five genes that cause obesity will provide new insight into the physiologic systems that regulate energy balance.

Animals↗
PubMed1996

Pyruvate and hepatic pyruvate dehydrogenase levels in rat strains sensitive and resistant to dietary obesity.

This study compared the effects of exogenous pyruvate and lactate on the serum levels of pyruvate, lactate, glucose, alanine, and insulin, as well as the activity of hepatic pyruvate dehydrogenase (PDH) in strains of rat that were either sensitive [Osborne-Mendel (OM)] or resistant (S5B/Pl) to high-fat diet-induced obesity. Serum pyruvate and lactate were significantly higher and glucose lower in ad libitum-fed OM rats, but these differences disappeared after an 18-h fast. The increase in pyruvate and lactate after exogenous pyruvate administration was significantly greater in S5B/Pl rats than OM rats. There were no differences in serum alanine with strain or diet. The total PDH activity was similar across strains and diets but the proportion of PDH in its activated form (PDHa) was decreased in ad libitum-fed S5B/Pl rats. Pyruvate injection increased insulin and hepatic PDHa activity in OM rats fed both high- and low-fat diets, but these responses were greatly attenuated or absent in S5B/Pl rats. The data are consistent with the hypothesis that modulation of carbohydrate oxidation by PDH may be related to susceptibility to obesity when rats are fed a high-fat diet.

Animals↗
PubMed1995

Differential effects of enterostatin, galanin and opioids on high-fat diet consumption.

Enterostatin, the activation peptide of pancreatic procolipase, suppresses high-fat diet consumption both centrally and peripherally. kappa-opioid agonists are also known to stimulate fat intake. These experiments were conducted to determine if an opioidergic central pathway might mediate the effects of enterostatin and galanin on fat intake. Male Sprague-Dawley rats were adapted to a high-fat diet (56% energy) and were implanted with cannulae aimed at the lateral cerebral ventricle (LV) or third cerebral ventricle (3V). Injection of enterostatin (1 nmol, LV) suppressed high-fat diet consumption in fasted (20 h) rats. This inhibition of high-fat intake by enterostatin was attenuated by central injection of the specific kappa-agonist U50488 (2.15, 21.5 and 215 nmol, LV) in a dose-dependent manner in fasted rats while only the highest dose of U50488 (215 nmol, LV) independently produced stimulation of high-fat diet consumption in sated rats. Galanin (0.1 nmol, 3V) induced consumption of high-fat diet in sated rats similar to that seen with U50488 and this stimulation was attenuated by peripheral injection of naloxone (1.0 mg/kg i.p.). We present a model which integrates the present data, as well as previous findings, in explaining a potential common opioid pathway modulating fat consumption.

Animals↗
PubMed1995

Bombesin-induced hypothermia in rats tested at normal ambient temperatures: contribution of the sympathetic nervous system.

Rats infused centrally with bombesin become hypothermic at normal ambient temperatures when acutely deprived of food, but not while allowed unrestrained access to food. Ad lib-fed rats, tested at normal ambient temperatures, become hypothermic after receiving intracerebroventricular (ICV) bombesin when they have ventromedial hypothalamic lesions or when administered insulin or 2-deoxy-D-glucose peripherally. All of these conditions have been linked to reductions of sympathetic nervous system activity to brown adipose tissue (BAT), a major thermogenic mechanism of many homeotherms. A between group design was used to examine the effects of ICV bombesin infusions on the response to peripheral injections of a) the sympathetic ganglionic blocker chlorisondamine (2.5 mg/kg, IP) in ad lib-fed rats, b) the nonspecific beta-agonist isoproterenol (30 mg/kg, IP) in food-deprived rats, and c) the combination of isoproterenol and chlorisondamine in ad lib-fed rats. Ad lib-fed rats receiving ICV bombesin (100 ng/5 microliters), in combination with peripheral chlorisondamine injection, became hypothermic 60 min postbombesin administration (-2.84 +/- 0.33 degrees C), while ad lib-fed rats receiving ICV bombesin infusion and peripheral injections of saline did not (-0.08 +/- 0.37 degrees C). Isoproterenol blocked hyperthermia in ad lib-fed rats injected with chlorisondamine and ICV bombesin. Food-derived rats receiving ICV bombesin infusion and peripheral saline injection exhibited hypothermia 60 min postbombesin administration (-2.51 +/- 0.29 degrees C). Peripheral injections of isoproterenol prevented bombesin-induced hypothermia in food-deprived rats. These data suggest that bombesin induces hypothermia at normal ambient temperatures when the sympathetic nervous system drive to BAT cannot be (or is not) activated.

Adipose Tissue, Brown↗
PubMed1995

Regulation of beta 3-adrenergic receptor mRNA by sympathetic nerves and glucocorticoids in BAT of Zucker obese rats.

Impaired brown adipose tissue (BAT) thermogenesis in the genetically obese Zucker fatty (fa/fa) rat is restored to normal by adrenalectomy. We investigated the role of the sympathetic nervous system in modulating the effects of adrenalectomy by studying beta3-adrenergic receptor (AR) and uncoupling protein (UCP) mRNA levels in unilaterally sympathectomized interscapular BAT of lean and obese rats. UCP mRNA levels were increased by adrenalectomy. Sympathetic denervation prevented this adrenalectomy-induced increase in lean rats but not in obese rats. beta 3-AR mRNA was decreased in BAT of obese rats. Adrenalectomy decreased and denervation increased beta 3-AR mRNA in lean rats but the opposite response was observed to both of these manipulations in obese rats. beta 3-AR mRNA and UCP mRNA were negatively correlated in lean rats but positively correlated in obese rats. Norepinephrine increased UCP mRNA levels in denervated BAT of both lean and obese rats and decreased beta 3-AR mRNA in lean rats but not obese rats. These data suggest that the regulation of the beta 3-AR gene in response to sympathetic stimuli and glucocorticoids is abnormal in the obese rat.

Adipose Tissue, Brown↗
PubMed1994

Vagal-central nervous system interactions modulate the feeding response to peripheral enterostatin.

Enterostatin selectively inhibits the intake of dietary fat after both peripheral and central administration. We have investigated the role of the hepatic vagus nerve in modulating the peripheral response to enterostatin in Sprague-Dawley rats adapted to a high fat (HF) diet. Intraperitoneal (ip) enterostatin reduced intake of HF diet after overnight starvation. This response was abolished by selective vagal hepatic branch transection. Immunohistochemical techniques were used to identify the location of Fos protein in brain nuclei after ip enterostatin. Fos protein was evident in the nucleus tractus solitarius (NTS), parabrachial, paraventricular and supraoptic nuclei. The pattern of expression of Fos-like immunoreactivity differed from that induced by the lipoprivic agent beta-mercaptoacetate. Transection of the hepatic vagus blocked the central Fos responses to ip enterostatin. We conclude that afferent hepatic vagal nerve activity is required for the feeding response to peripheral enterostatin.

Animals↗
PubMed1994

Effects of clenbuterol, a beta 2-adrenoceptor agonist, on macronutrient selection in rats.

In these studies, clenbuterol, a beta 2-adrenergic agonist, was injected into male rats and the intake of a three-choice macronutrient diet was measured. The intakes of fat and protein were selectively inhibited by clenbuterol in both overnight-fasted and freely fed rats. There was no effect of clenbuterol on carbohydrate intake. Prior administration of nadolol, a beta-adrenergic antagonist, which does not easily pass the blood-brain barrier, completely antagonized the anorectic effect of clenbuterol. However, section of the hepatic branch of the vagus nerve did not abolish the nadolol effect. These results suggest that the anorectic effect of clenbuterol is mediated by peripheral beta 2-adrenergic receptors rather than central beta 2-adrenoceptors, and is not related to information transmitted from the liver via the vagus nerve.

Afferent Pathways↗