Biomedical subjects

Myrtha Arnold

Publications and source records attributed to Myrtha Arnold.

9 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 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

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↗

PubMed2004

Particle size reduction and encapsulation affect the bioavailability of ferric pyrophosphate in rats.

Particle size is an important determinant of Fe absorption from poorly soluble Fe compounds in foods. Decreasing the particle size of elemental iron powders increases their absorption. The effect of a reduction in particle size on the bioavailability of ferric pyrophosphate (FePP) is unclear. Encapsulation of iron compounds for food fortification may protect against adverse sensory changes, but at the same time may reduce bioavailability. The hemoglobin (Hb) repletion method in weanling Sprague-Dawley rats (n = 100) was used to compare the relative bioavailability (RBV) of 4 forms of FePP: 1) regular FePP [mean particle size (MPS) approximately 21 microm]; 2) MPS approximately 2.5 microm; 3) MPS approximately 2.5 microm encapsulated in hydrogenated palm oil; and 4) MPS approximately 0.5 microm with emulsifiers. The RBV compared with ferrous sulfate was calculated by the slope-ratio technique. The RBV was 43% for encapsulated MPS approximately 2.5 microm, significantly lower than the other FePP compounds (P < 0.05), 59% for the regular FePP, and 69% for MPS approximately 2.5 microm, not different from each other but significantly lower than ferrous sulfate (P < 0.05), and 95% for emulsified MPS approximately 0.5 microm, comparable to ferrous sulfate. Encapsulation of FePP with hydrogenated palm oil at a capsule:substrate ratio of 60:40 decreased RBV. Particle size reduction increases the RBV of FePP and may make this compound more useful for food fortification.

Animals↗

PubMed2002

Iron deficiency anemia reduces thyroid peroxidase activity in rats.

Studies in animals and humans have shown that iron deficiency anemia (IDA) impairs thyroid metabolism. However, the mechanism is not yet clear. The objective of this study was to investigate whether iron (Fe) deficiency lowers thyroid peroxidase (TPO) activity. TPO is a heme-containing enzyme catalyzing the two initial steps in thyroid hormone synthesis. Male weanling Sprague-Dawley rats (n = 84) were randomly assigned to seven groups. Three groups (ID-3, ID-7, ID-11) were fed an Fe-deficient diet containing 3, 7 and 11 microg Fe/g, respectively. Because IDA reduces food intake, three control groups were pair-fed Fe-sufficient diets (35 microg Fe/g) to each of the ID groups and one control group consumed food ad libitum. After 4 wk, hemoglobin, triiodothyronine (T(3)) and thyroxine (T(4)) were lower in the Fe-deficient groups than in the ad libitum control group (P < 0.001). By multiple regression, food restriction had a significant, independent effect on T(4) (P < 0.0001), but not on T(3). TPO activity (by both guaiacol and iodine assays) was markedly reduced by food restriction (P < 0.05). IDA also independently reduced TPO activity (P < 0.05). Compared with the ad libitum controls, TPO activity per thyroid determined by the guaiacol assay in the ID-3, ID-7 and ID-11 groups was decreased by 56, 45 and 33%, respectively (P < 0.05). These data indicate that Fe deficiency sharply reduces TPO activity and suggest that decreased TPO activity contributes to the adverse effects of IDA on thyroid metabolism.

Anemia, Iron-Deficiency↗