bluuebunny/crossref_metadata_2025 huggingface dataset:
Transplantation of lean fetal hypothalamus restores hypothalamic function in Zucker obese rats
Authors: Fukagawa K. , Knight D. S. , Price H. V. , Sakata T. , Tso P.
Published: December 2017

Rats with lesions to the ventromedial hypothalamus (VMH) manifest obesity, hyperphagia, and hyperinsulinemia, and fetal VMH transplantation into the third cerebroventricle of VMH-lesioned rats reduces the development of obesity caused by the lesion. The aim of this study was to determine whether the hyperphagia, hyperlipidemia, and hyperinsulinemia of obsese Zucker rats could be corrected by the transplantation of lean fetal Zucker hypothalamic tissue into the third cerebral ventricle of Zucker obese rats. After the fetal hypothalamic transplant (obese-HY), the rate of weight gain was significantly diminished compared with the unoperated Zucker obese rats and the obese rats that received the transplantation of a similar amount of frontal cortical tissue from the same fetus (obese-FC). Food intake was significantly lower, and plasma triacylglycerol and insulin concentrations were also significantly reduced in the obese-HY rats compared with the obese and obese-FC rats. The weight of the adrenal glands, the plasma adrenocorticotropic hormone concentration, the liver weight, and the liver lipid content in obese-HY were significantly less than those observed in the obese and obese-FC animals. There were no significant differences between the obese and the obese-FC animals or between unoperated Zucker lean rats and lean rats transplanted with lean fetal hypothalamus in all the parameters we determined in this study. Neovascularization and normal cellular morphology of the transplanted fetal hypothalamic tissue suggest that the transplanted neural and glial cells were viable and physiologically functional. In conclusion, this study offers evidence suggesting that the hypothalamic-pituitary-adrenal function is defective in Zucker obese rats, resulting in excessive weight gain, hyperphagia, hyperlipidemia, and hyperinsulinemia. The hypothalamic dysfunction in the Zucker obese rats is corrected by the transplantation of lean fetal hypothalamus.
Glycogen depletion of the intrafusal fibers in a mouse muscle spindle during prolonged swimming
Authors: Yoshimura A. , Shimomura Y. , Murakami T. , Ichikawa M. , Nakai N. , Fujitsuka C. , Kanematsu M. , Fujitsuka N.
Published: December 2017

This study investigated the recruitment of different types of intrafusal fibers during prolonged swimming at 60-75% of VO2max. We used 56 male adult mice and examined depletion of glycogen in soleus (Sol) and extensor digitorum longus (EDL) muscle spindles by visual inspection and a newly developed optical scanning method. More than 80% of all spindles from six mice consisted of four fibers: one type I nuclear bag (bag1) fiber, one type II nuclear bag (bag2) fiber, and two nuclear chain fibers. Glycogen content was estimated in muscle fibers from groups of six mice that had rested or swum for either 0.5, 1, 2, 4, or 8 h. The optical scanning intensity of periodic acid Schiff (PAS)-stained sections was correlated with their biochemically determined glycogen content (r = 0.93). Both methods showed fundamentally the same result: each type of intrafusal fiber has its own typical recruitment pattern during exercise. In the initial phase (0-0.5 h), glycogen depletion was largest in nuclear bag1 fibers and insignificant in the bag2 and chain fibers. With the bag1 fibers having become fatigued, nuclear bag2 fibers mainly took over during the middle phase (2-4 h). During the last phase (4-8 h), only the glycogen content of chain fibers decreased significantly (4-8 h). There were significant correlations between the recruitment pattern of bag1 and extrafusal type I fibers in both Sol and EDL, between nuclear bag2 and type IIa fibers in Sol, and between nuclear chain and type IIb fibers in EDL. This suggests that, during moderately intense exercise, glycogen depletion occurs first in the slow, then the intermediate, and, finally, the fast intrafusal fibers.
Is the onset of obesity in suckling fa/fa rats linked to a potentially larger milk intake?
Authors: Buchberger P. , Schmidt I.
Published: December 2017

We wanted to find out whether fatty (fa/fa) sucklings show abnormal intake when given access to an abundant milk reservoir. To do this, we gravimetrically determined the milk ingested by small groups (4-5 pups) of 5- to 15-day-old lean (+/fa) and fatty littermates allowed to suckle for 30 min after their mother had not been nursing for periods of between 1 and 7 h. The pups were grouped randomly and their phenotypes retrospectively identified. Within both genotypes, the intakes of simultaneously tested pups were significantly higher in pups deprived for longer periods. Deprived and undeprived fa/fa pups ingested, however, slightly but significantly less milk than +/fa littermates did in the same nursing bout. In the first 2 wk of life, when fa/fa pups deposit nearly twice as much body fat as their +/fa littermates do, fa/fa pups will thus suckle less rather than more milk. This extends previous findings showing that the onset of fa/fa obesity is independent of larger intakes and thus questions that fa impairs a receptor primarily controlling food intake.
Alpha-adrenergic stimulation of thermogenesis in a rat kangaroo (Marsupialia, Bettongia gaimardi)
Authors: Ye J. M. , Edwards S. J. , Rose R. W. , Steen J. T. , Clark M. G. , Colquhoun E. Q.
Published: December 2017

The Tasmanian bettong (Bettongia gaimardi) is a small rat kangaroo without detectable brown adipose tissue (BAT). In view of our previous findings of norepinephrine-mediated increase in O2 consumption (Vo2) in the perfused hindlimb of this species, the present study examined the effect of alpha-adrenoceptors on the thermogenesis of conscious bettongs at rest by infusing adrenergic agents via an indwelling catheter in the tail vein. The resting Vo2 was 22.9 +/- 1.9 mmol.kg-1.h-1. Norepinephrine (10-80 micrograms.kg-1.min-1) stimulated Vo2 in a dose-dependent manner with the maximal increment of 46.7%. Naphazoline (an alpha 1,alpha 2-adrenergic agonist) and phenylephrine (an alpha 1-adrenergic agonist) also elicited increases in Vo2 with maximal values of 29.6 and 34.8%, respectively. In contrast, the alpha 2-adrenergic agonist clonidine had no significant effects. Both alpha- and beta-adrenergic blockers were used to antagonize the submaximal increase in Vo2 elicited by norepinephrine. As a dose of 10 micrograms.kg-1.min-1, the alpha-adrenergic blocker phentolamine abolished the effects of naphazoline and phenylephrine and reduced norepinephrine-induced Vo2 by 45.5%. The beta-adrenergic blocker propranolol inhibited the norepinephrine-induced Vo2 by 58.8% at 20 micrograms.kg-1.min-1. A combination of the two antagonists blocked 82.5% of the norepinephrine-induced Vo2. Pretreatment of the animal with indomethacin (1 mg/kg), a known inhibitor of prostaglandin cyclooxygenase, had no effect on phenylephrine-elicited Vo2. Taken together, these results indicate that alpha 1-adrenoceptors are directly involved in norepinephrine-induced thermogenesis in non-BAT tissue(s).
Opioid growth factor ([Met5]enkephalin) prevents the incidence and retards the growth of human colon cancer
Authors: Zagon I. S. , Hytrek S. D. , Lang C. M. , Smith J. P. , McGarrity T. J. , Wu Y. , McLaughlin P. J.
Published: December 2017

Endogenous opioid peptides serve as growth factors in normal and neoplastic cells and tissues, and both opioids and their receptors have been identified in human colon cancer. This study examined the hypothesis that opioids serve to modulate the growth of human colon cancer. Daily administration of the native opioid growth factor (OGF), [Met5]enkephalin, at dosages of 0.5, 5, or 25 mg/kg prevented the occurrence of human colon cancer HT-29 xenografts in nude mice. More than 80% of the mice receiving OGF beginning at the time of tumor cell inoculation did not exhibit neoplasias within 3 wk, in comparison with a tumor incidence of 93% in control subjects. Even 7 wk after cancer cell inoculation, 57% of the mice given OGF did not display a tumor. OGF delayed tumor appearance and growth in animals developing colon cancer with respect to the control group. The suppressive effects of OGF on oncogenicity were opioid receptor mediated. OGF and its receptor, zeta (zeta), were detected in transplanted human HT-29 colon tumors. Surgical specimens of human colon cancers also contained OGF. These results show that a naturally occurring opioid peptide acts as a potent negative regulator of human gastrointestinal cancer and may suggest pathways for tumor etiology, progression, treatment, and prophylaxis.
Respiratory motor responses to cranial nerve afferent stimulation in rats
Authors: Hayashi F. , McCrimmon D. R.
Published: December 2017

It was hypothesized that, because rats appear to lack a prominent disynaptic projection from the dorsal respiratory group to phrenic motoneurons (Phr), they would lack the short-latency excitation of Phr output seen in cats in response to stimulation of some cranial nerve afferents. Single-pulse superior laryngeal nerve (SLN) stimulation elicited a short-latency bilateral excitation of glossopharyngeal (IX) and hypoglossal (XII) nerves and an ipsilateral excitation of pharyngeal branch of vagus (PhX) in 67% of rats, but no excitation of Phr. Vagus (X) stimulation elicited a bilateral excitation of Phr and a predominantly ipsilateral excitation of IX and PhX. Single-pulse stimulation of SLN or X also elicited longer-latency, bilateral decreases in activity of all recorded nerves. Repetitive stimulation (50 Hz) of SLN or X suppressed inspiratory activity and prolonged expiration. Lung inflation (7.5 cmH2O) inhibited Phr and PhX activity; X stimulation inhibited Phr but prolonged PhX activity. In conclusion, rats predictably lack the SLN-induced short latency Phr excitation but exhibit other short latency reflexes for which the underlying circuitry is not clear.
Age-related alterations in the fractal scaling of cardiac interbeat interval dynamics
Authors: Iyengar N. , Peng C. K. , Morin R. , Goldberger A. L. , Lipsitz L. A.
Published: December 2017

We postulated that aging is associated with disruption in the fractallike long-range correlations that characterize healthy sinus rhythm cardiac interval dynamics. Ten young (21-34 yr) and 10 elderly (68-81 yr) rigorously screened healthy subjects underwent 120 min of continuous supine resting electrocardiographic recording. We analyzed the interbeat interval time series using standard time and frequency domain statistics and using a fractal measure, detrended fluctuation analysis, to quantify long-range correlation properties. In healthy young subjects, interbeat intervals demonstrated fractal scaling, with scaling exponents (alpha) from the fluctuation analysis close to a value of 1.0. In the group of healthy elderly subjects, the interbeat interval time series had two scaling regions. Over the short range, interbeat interval fluctuations resembled a random walk process (Brownian noise, alpha = 1.5), whereas over the longer range they resembled white noise (alpha = 0.5). Short (alpha s)- and long-range (alpha 1) scaling exponents were significantly different in the elderly subjects compared with young (alpha s = 1.12 +/- 0.19 vs. 0.90 +/- 0.14, respectively, P = 0.009; alpha 1 = 0.75 +/- 0.17 vs. 0.99 +/- 0.10, respectively, P = 0.002). The crossover behavior from one scaling region to another could be modeled as a first-order autoregressive process, which closely fit the data from four elderly subjects. This implies that a single characteristic time scale may be dominating heartbeat control in these subjects. The age-related loss of fractal organization in heartbeat dynamics may reflect the degradation of integrated physiological regulatory systems and may impair an individual's ability to adapt to stress.
Photoperiod-dependent correlation between light-induced SCN c-fos expression and resetting of circadian phase
Authors: Travnickova Z. , Sumova A. , Peters R. , Schwartz W. J. , Illnerova H.
Published: December 2017

In rodents, brief light pulses that shift the phase of the circadian locomotor rhythm also increase c-fos gene expression in the suprachiasmatic nucleus (SCN), site of an endogenous clock that regulates such rhythmicity. Because the magnitude of photic phase shifts varies when light pulses are applied at different time points over the course of the subjective night, we examined the degree of SCN c-fos gene expression after single 30-min light pulses were delivered at time points that spanned the early and late subjective night in rats maintained in either short (8:16-h light-dark cycle) or long (16:8-h light-dark cycle) photoperiods. The light-induced level of c-fos mRNA and the number of cells expressing immunoreactive c-Fos protein were measured in the SCN by in situ hybridization and immunohistochemistry, respectively, and compared with the magnitude of the corresponding phase shifts of the circadian rhythm of pineal N-acetyltransferase (NAT) activity. We found a robust correlation between c-fos photoinduction and NAT phase shifts, but this relationship was dependent on photoperiod. The degree of c-fos gene expression was strongly correlated with the magnitude of NAT phase advances and delays under the short photoperiod and with phase advances under the long photoperiod, but not with phase delays under the long photoperiod. The data suggest that c-fos gene expression in the SCN may be involved in the photic resetting of the pineal NAT rhythm. Under the long photoperiod, however, the magnitude of phase delays may be limited by the functional state of the circadian pacemaking system.
Development of cardiovascular responses to hypoxia in larvae of the frog Xenopus laevis
Authors: Fritsche R. , Burggren W.
Published: December 2017

Cardiovascular responses (blood pressure, heart rate, stroke volume, cardiac output, and peripheral vascular resistance) to acute hypoxia (Po2 = 70 mmHg) in developing larvae of Xenopus laevis from Nieuwkoop-Faber (NF) stage 45 and up to newly metamorphosed froglets were investigated. The results revealed two distinct response patterns to acute hypoxia in "early" (NF stages 45-48 and 49-51) and "late" (NF stages 52-53, 54-57, and 58-62) larval Xenopus. The early larvae responded to acute hypoxia with a significantly decreased stroke volume, cardiac output, and blood pressure. Peripheral resistance increased, whereas no change in heart rate occurred. In late larvae, stroke volume and blood pressure increased during acute hypoxia, but an offsetting bradycardia prevented major changes in cardiac output. We conclude that, up to stage 51 of development, hypoxia exerts a direct inhibitory effect on the heart and smooth muscle of the blood vessels, with no Frank-Starling relationship apparent. Older larvae show evidence of both intrinsic and extrinsic regulation of the cardiovascular system in response to acute hypoxia, suggesting that there is a specific point in larval development when cardiovascular regulation during hypoxia is expressed.
Interactions between postprandial thermogenesis, sensory stimulation of feeding, and hunger
Authors: LeBlanc J. , Soucy J.
Published: December 2017

An early thermogenic response has been described following the ingestion of palatable food. This study was designed to investigate the possible relationship between this so-called cephalic response, the sensory stimulation of feeding, and the declining feeling of hunger as the meal progresses. O2 consumption, carbohydrate and lipid oxidation, as well as ratings of hunger were measured in four experimental situations in which the subjects, after overnight fast, ate either two small caramel cakes at one time or the same amount of calories divided in eight portions that were eaten at 10-min intervals. The third experiment, the sham-feeding experiment, was similar to the last one except that the food was spit out instead of being swallowed after being chewed. A control experiment was added in which no food was given but during which the subject mimicked the act of chewing as was done in the preceding experiment. A small increase in O2 consumed was observed in the control experiment. After the one-meal experiment, the increase was larger for the first 90 min and declined thereafter. During the first 40 min of the sham-feeding experiment, O2 consumption increased more than when the eight meals were eaten, indicating that during this period the sensory stimulation per se is responsible for the cephalic thermic response to food. At 90 min, the ratings of hunger were diminished not only in the eight meals experiment but in the eight sham meals experiment as well, showing the role of sensory stimulation in the control of hunger. These results indicate a possible causal relationship between the cephalic thermogenesis, the control of hunger, and the prandial sensory stimulations.
Efficient oligonucleotide delivery using the HVJ-liposome method in the central nervous system
Authors: Yamada K. , Moriguchi A. , Morishita R. , Aoki M. , Nakamura Y. , Mikami H. , Oshima T. , Ninomiya M. , Kaneda Y. , Higaki J. , Ogihara T.
Published: December 2017

We examined the efficiency and intracellular fate of oligodeoxy-nucleotides (ODN) in the central nervous system (CNS) after delivery with a hemagglutinating virus of Japan (HVJ)-liposome vector in vivo and in vitro. In primary cultured granular cells of the rat cerebellum, application of fluorescein isothiocyanate (FITC)-labeled ODN complexed with HVJ-liposomes in vitro resulted in strong fluorescence localized in nuclei that persisted for > or = 2 wk, in contrast to 3 days with ODN alone. In vivo ODN transfer was attempted by different approaches: infusions into the paraventricular nuclei of the hypothalamus and the lateral cerebroventricle. Injection of FITC-labeled ODN into the hypothalamus by the HVJ-liposome method produced a higher concentration and more persistent fluorescence than did injection of ODN alone. Administration of ODN into the lateral cerebroventricle with HVJ-liposomes yielded more conspicuous and prolonged fluorescence in the periventricular layer, predominantly in cell nuclei. Furthermore, the distribution of fluorescent cells was broader with the HVJ-liposome method. These results indicate that the HVJ-liposome method prolongs the half-life of ODN and concentrates them in cell nuclei. Thus it is an efficient method for ODN transfer and holds promise as a gene delivery method in the CNS.
A comparison of the metabolic cost of protein synthesis in stenothermal and eurythermal isopod crustaceans
Authors: Whiteley N. M. , Taylor E. W. , el Haj A. J.
Published: December 2017

To examine the presence of metabolic cold adaptation in Antarctic isopods, whole animal rates of oxygen uptake (MVo2) and protein synthesis were measured in Glyptonotus antarcticus at 0 degree C and compared with the temperature isopod Idotea rescata at 4 and 14 degrees C. The specific relationship between rates of metabolism and protein synthesis was investigated by injecting animals with cycloheximide, a protein synthesis inhibitor. In G. antarcticus, routine MVo2 was 11.10 +/- 0.89 mumol.kg-1.min-1 (n = 19 animals), and ks was 0.24 +/- 0.04% protein synthesized/day (n = 8 animals). Comparison with I. rescata showed that standardized whole animal MVo2 decreased with temperature (temperature quotient = 1.99), but whole animal ks was considerably lower in the Antarctic isopod; 66 and 22% of total MVo2 was attributable to protein synthesis in G. antarcticus at 0 degree C and I. rescata at 4 degrees C, respectively. The energetic cost of protein synthesis was four times higher in G. antarcticus at 885 +/- 141 mmol ATP/g protein (n = 5 animals) compared with 237 +/- 76 mmol ATP/g protein (n = 6) in I. rescata. G. antarcticus does not show metabolic rate compensation and maintains extremely low ks levels because of the relatively high energetic cost of protein synthesis.
Natural hypothermia and sleep deprivation: common effects on recovery sleep in the Djungarian hamster
Authors: Deboer T. , Tobler I.
Published: December 2017

Sleep, daily torpor, and hibernation have been considered to be homologous processes. However, in the Djungarian hamster, daily torpor is followed by an increase in slow-wave activity (SWA; electroencephalogram power density 0.75-4.0 Hz) that is similar to the increase observed after sleep deprivation. A positive correlation was found between torpor episode length and the subsequent increase in SWA, which was highest when SWA was assumed to increase with a saturating exponential function. Thus the increase in SWA propensity during daily torpor followed similar kinetics as during waking, supporting the hypothesis that when the animal is in torpor it is incurring a sleep debt. An alternative hypothesis, proposing that the mode of arousal causes the subsequent SWA increase, was tested by warming the animals during emergence from daily torpor. Irrespective of mode of arousal, more non-rapid eye movement (NREM) sleep and a similar SWA increase was found after torpor. The data are compatible with a putative neuronal restorative function for sleep associated with the expression of SWA in NREM sleep. During torpor, when brain temperature is low, this function is inhibited, whereas the need for restoration accumulates. Recovery takes place only after return to euthermia.
Zinc kinetics in preterm infants: a compartmental model based on stable isotope data
Authors: Wastney M. E. , Angelus P. , Barnes R. M. , Subramanian K. N.
Published: December 2017

Zinc is an essential nutrient for growth; however, little is known about zinc kinetics (absorption, distribution, and excretion) in preterm infants (< 38-wk gestation). Zinc kinetics were studied in two preterm infants (gestational ages, 32 and 33 wk) following oral or intravenous administration of a stable isotope (70Zn). Plasma, red blood cells (RBC), urine, and feces were sampled for up to 30 days. Isotope enrichment was measured in tissues by inductively coupled plasma (ICP)-mass spectrometry, and zinc was determined by ICP-atomic emission spectrometry. Data were analyzed by compartmental analysis using SAAM31. Zinc intake increased during the studies, and, because body zinc was not in steady state, both tracer (70Zn) and tracee (Zn) data were fitted using analogous models. A model for adults [M. E. Wastney, R. L. Aamodt, W. F. Rumble, and R. I. Henkin. Am. J. Physiol. 251 (Regulatory Integrative Comp. Physiol. 20): R398-R408, 1986] was modified to fit data from the preterm infants. RBC data were fitted using one compartment (vs. 2 in adults), and an adult RBC subsystem was included in the model to account for zinc introduced during blood transfusions. Exchange of zinc between compartments that were not sampled was based on zinc distribution in neonates. Absorption was 42 and 34%, and endogenous fecal excretion, based on intravenous data, was 15 micrograms.kg-1.day-1. The model can be used to quantify changes in zinc kinetics of preterm infants with age, weight, and zinc intake for evaluating nutritional requirements with growth.
Role of cholecystokinin in the anorexia produced by duodenal delivery of glucose in rats
Authors: Woltman T. , Reidelberger R.
Published: December 2017

We used the type A cholecystokinin receptor (CCK-AR) antagonist devazepide to assess the importance of CCK in mediating the anorexia produced by 2-h duodenal infusions of glucose (9.2, 11.0, and 18.3 mmol.kg-1.h-1) and the glucose dimer maltose (4.5, 6.7, and 8.5 mmol.kg-1.h-1) at the start of the dark period in nonfasted rats with free access to food. Glucose and maltose appeared to inhibit 2- to 3-h food intakes dose dependently from 19 to 91%. The highest doses of glucose and maltose administered suppressed feeding similarly by increasing first meal latency and decreasing meal frequency; lower doses produced less reliable effects on meal patterns. Devazepide appeared to completely reverse the cumulative intake responses and some of the meal pattern responses to the 9.2-mmol.kg-1.h-1 dose of glucose and to partially attenuate responses to the two higher glucose doses and to the minimal effective dose of maltose (6.7 mmol.kg-1.h-1). The magnitudes of these devazepide effects were not statistically different from those produced by devazepide when vehicle was infused duodenally. These results suggest that CCK may play a significant necessary role in mediating the satiety response to duodenal delivery of small but not large loads of glucose.
Ontogeny of blood-brain barrier function in ovine fetuses, lambs, and adults
Authors: Stonestreet B. S. , Patlak C. S. , Pettigrew K. D. , Reilly C. B. , Cserr H. F.
Published: December 2017

The ontogeny of regional blood-brain barrier function was quantified with the rate constant for influx (Ki) across the blood-brain barrier with the small molecular weight synthetic, inert hydrophilic amino acid alpha-aminoisobutyric acid (AIB) in chronically instrumented early (87 days of gestation, 60% of gestation) and late (137 days of gestation, 90% of gestation) gestation fetal, newborn (3 days of age), older (24 days of age), and adult (3 years of age) sheep. The Ki was significantly (P < 0.05) lower in the brain regions of the adult sheep and in most brain regions of newborn and older lambs compared with fetuses at 60 and 90% of gestation. The Ki exhibited regional brain heterogeneity (P < 0.05) in the five groups. The patterns of regional heterogeneity were accentuated (P < 0.05) in the younger groups. We conclude that ontogenic decreases in blood-brain barrier permeability are observed in ovine fetuses from 60% of gestation to maturity in the adult.
Unilateral smoke inhalation in sheep: effect on left lung lymph flow with right lung injury
Authors: Kikuchi Y. , Traber L. D. , Herndon D. N. , Traber D. L.
Published: December 2017

We previously reported that smoke inhalation to the right lung will result in damage to the air-insufflated left lung. In this study we confirm these findings and determine whether this injury is associated with an elevation in lung lymph flow and pulmonary microvascular permeability to protein as indexed by changes in reflection coefficient. Sheep (n = 12) were surgically prepared by placement of a Swan-Ganz catheter and pneumatic occluders on all pulmonary veins and the left pulmonary artery. The left lung lymphatic was selectively cannulated as shown previously (Y. Kikuchi, H. Nakazawa, and D. Traber. Am. J. Physiol. 269 (Regulatory Integrative Comp. Physiol. 38): R943-R947, 1995). All afferent lymphatics from the right lung were severed, and the right pulmonary ligament was sectioned. The caudal end of the lymph node was sectioned to remove systemic lymph contamination. The sheep were studied in the unanesthetized state 7 days later. To ensure that lymph flow was exclusively from the left lung (QLL), right pulmonary microvascular pressure was increased, a procedure that resulted in little or no change in QLL, as was previously shown. The sheep were then anesthetized, and a Carlens tube was positioned to allow separate ventilation of the right and left lung. The right lungs of five sheep and the left lungs of two sheep were insufflated with cotton smoke. Insufflation of the left lung with cotton smoke produced a fourfold increase in QLL that began 4 h after insult. Insufflation of the right lung with smoke led to a doubling of QLL that began 12 h after insult. Changes in QLL were associated with increased microvascular permeability, as indexed by the reflection coefficient. Control sheep (air insufflated into both lungs, n = 5) showed no change in QLL. Injury to the right lung resulted in damage to the left air-insufflated lung, suggesting a hematogenous mediation of the response.
Chronic infusion of islet amyloid polypeptide causes anorexia in rats
Authors: Arnelo U. , Permert J. , Adrian T. E. , Larsson J. , Westermark P. , Reidelberger R. D.
Published: December 2017

Islet amyloid polypeptide (IAPP) is a hormonal peptide that at high doses has been shown to reduce food intake. In the present study, the dose-response effects of subcutaneous infusion of IAPP (0, 2, 7, and 25 pmol.kg-1.min-1) for 8 days on food intake and meal patterns in rats were investigated. At the end of the experiment, plasma was obtained and levels of IAPP were measured by radioimmunoassay. IAPP dose-dependently and transiently inhibited food intake. The minimal effective dose (2 pmol.kg-1.min-1) caused a small but significant (up to 14%, P < 0.01) inhibition of food intake that lasted 5 days. The highest dose administered (25 pmol.kg-1.min-1) had the greatest effect (up to 44%, P < 0.001), which lasted throughout the 8-day period. Reductions in feeding during light and dark phases occurred through a decrease in number of meals consumed rather than meal size or meal duration. IAPP also decreased body weight gain and water intake dose dependently. IAPP infusion of 2, 7, and 25 pmol.kg-1.min-1 increased plasma IAPP concentrations from a basal level of 10.3 +/- 0.7 pM to 35.1 +/- 5.4, 78.1 +/- 11.2, and 236.6 +/- 23.6 pM, respectively, values that are likely to be close to physiological and within the pathophysiological ranges. Thus IAPP may play an important physiological or pathophysiological role in control of food intake.
Vectorial efflux of cGMP and its dependence on sodium in the cortical collecting duct
Authors: Stoos B. A. , Garvin J. L.
Published: December 2017

Guanosine 3',5'-cyclic monophosphate (cGMP) is an important second messenger that regulates transport in the nephron. We propose that the transport mechanisms that remove cGMP from the cell are different in the luminal and basolateral membranes of the cortical collecting duct (CCD). We examined efflux of cGMP from cultured and isolated perfused CCDs in response to atrial natriuretic factor (ANF) and nitric oxide (NO). In the presence of phosphodiesterase inhibition, these compounds resulted in preferential efflux of cGMP across the basolateral membrane in both cultured and isolated CCDs. In the presence of ANF, efflux was five times higher across the basolateral than the luminal membrane in cultured CCD cells (n = 14). In isolated CCDs, effluxes across the basolateral and luminal membranes were 1.02 +/- 0.2 and 0.03 +/- 0.01 fmol.mm-1.min-1, respectively, in the presence of ANF (n = 6; P < 0.007) and 0.87 +/- 0.21 and 0.02 +/- 0.01 fmol.mm-1.min-1, respectively, in the presence of NO (n = 6; P < 0.011). Efflux across the basolateral membrane in the presence and absence of sodium was 37 +/- 7.3 and 19.9 +/- 5 fmol.cm-2.min-1, respectively, in cultured cells (n = 12; P < 0.044) and 1.02 +/- 0.2 (n = 6) and 0.41 +/- 0.12 (n = 5) fmol.mm-1.min-1 in isolated perfused tubules (P < 0.042). There was no difference in luminal transport in the presence and absence of sodium in either model. We conclude that there are at least two different mechanisms involved in the removal of cGMP from the cell, one sodium dependent and the other sodium independent. The basolateral membrane appears to contain both, whereas the luminal membrane contains only the sodium-independent mechanism.
Synergistic effect of acidification and hypoxia: in vivo 31P-NMR and respirometric study in fishes
Authors: van Ginneken V. , van den Thillart G. , Addink A. , Erkelens C.
Published: December 2017

We used 31P nuclear magnetic resonance (31P-NMR) spectroscopy to measure intracellular pH (pHi) and high-energy phosphate levels of white muscle of the fish tilapia (Oreochromis mossambicus) during exposure to the stressors hypoxia and water acidification separately and simultaneously. The protocol for the graded hypoxia load was 100, 40, 30, 20, 10, 5, and 3% air saturation for 1 h at each level. For environmental acidosis the pH of the water was lowered from 7.6 to 4.0 over 6 h, with time of exposure approximately 11 h. All protocols were followed by 6 h of reoxygenation at 20 degrees C. We also measured total oxygen consumption of the animal. The results of this in vivo study revealed that environmental acidification had no effect on oxygen consumption, pHi, or phosphocreatine depletion. Hypoxia caused moderate changes in these parameters and fast and complete recovery during reoxygenation. In contrast, the combination of environmental acidosis and hypoxia resulted in 50% mortality, increased depletion of the phosphocreatine pool, and a retarded recovery of the pHi during reoxygenation compared with the group with hypoxia as a single stressor. The combination of environmental acidification and hypoxia has a more profound effect and works synergistically compared with the conditions imposed separately. To investigate whether an adaptation response occurred during chronic exposure to environmental acidification, animals were exposed for 6 wk to pH 4.0 before experimentation. The pHi in the white muscle dropped from 7.2 (control group) to 6.9 during this period, whereas no effect was found in the phosphorylated compounds and oxygen consumption. Therefore, it is concluded that no adaptation response occurs in animals exposed to long-term environmental acidosis.
Corticosterone inhibition of osmotically stimulated vasopressin from hypothalamic-neurohypophysial explants
Authors: Papanek P. E. , Sladek C. D. , Raff H.
Published: December 2017

Glucocorticoids inhibit and glucocorticoid deficiency increases vasopressin (AVP) release in vivo. To determine whether the effect of glucocorticoids is hypothalamic and mediated via a glucocorticoid receptor, explants of the hypothalamic-neurohypophysial system were used to measure AVP release during agonist and antagonist exposure. Explants from adult rats, which contained AVP neurons of the supraoptic nucleus with axonal projections terminating in the neural lobe but excluded the paraventricular nucleus, were perifused with an osmotic stimulus (increase of 5 mosmol/h over 6 h) in the absence or presence of corticosterone (100 micrograms/dl) or with corticosterone (100 micrograms/dl) in the absence or presence of the glucocorticoid antagonist RU-486 (10 microM). AVP release was not increased during osmotic stimulation in the presence of corticosterone (Cort) and was 20-30% lower than osmotically stimulated release observed in the absence of Cort. RU-486 reversed the inhibitory effect of corticosterone on AVP release. No changes in AVP mRNA content were detected. These results suggest that Cort inhibits osmotically stimulated AVP release by a direct effect within the hypothalamus and/or neurohypophysis. This effect is mediated by the glucocorticoid receptor through either genomic or nongenomic mechanisms.
Eye and gonad: role in the dual-oscillator circadian system of female Japanese quail
Authors: Underwood H. , Siopes T. , Edmonds K.
Published: December 2017

Experiments were conducted to determine the anatomic and physiological basis of the dual-oscillator circadian system of female Japanese quail. After blocking of ocular light perception by eye-patching, the circadian body temperature rhythm dissociates into two circadian components in continuous lighting (LL). One component free runs with a period significantly shorter than 24 h [mean period (tau) = 22.7 h] and is driven by an ocular pacemaker, whereas the other component free runs with a period significantly longer than 24 h (tau = 26.3 h). The long free-running rhythm is driven by the same circadian clock that drives the circadian rhythm of ovulation. The expression of the long free-running rhythm in LL depends on the presence of the ovary: body temperature rhythmicity is abolished by ovariectomy. The two free-running oscillators in eye-patched birds showed evidence of mutual interaction. Significantly, the phase relationships that occur as the two oscillators interact can determine whether or not ovulation occurs. The results are discussed in terms of an "internal coincidence" mechanism for photoperiodic time measurement.
Involvement of the medial preoptic area in the anorectic action of estrogens
Authors: Dagnault A. , Richard D.
Published: December 2017

The implication of the medial preoptic area (MPOA) as a site for estrogen in the regulation of energy balance was investigated. Food intake, O2 consumption (VO2), and CO2 production were measured in ovariectomized rats injected with estradiol (E2) in the medial preoptic nucleus (MPN). Moreover, knowing the potential for corticotropin-releasing factor (CRF) in the anorectic effects of estrogens, we identified estrogen receptors (ER) colocalized in CRF-containing cells of the MPOA and how MPN injections of CRF compared with estrogen injections with respect to VO2 and the VO2-to-CO2 production ratio (respiratory quotient RQ). These energy balance measurements after the injections of four different doses of E2 or CRF were carried out in meal-fed rats chronically implanted with a guide cannula targeted to the MPN. The identification of cells colocalizing ER and CRF was determined using a double-immunostaining procedure revealing ER and CRF immunoreactivities with two different couplers. The injection of E2 into the MPN induced a dose-dependent reduction in food intake, whereas it did not affect VO2 or RQ. Conversely, the injection of CRF into the MPN had no effect on food intake but increased VO2 and decreased RQ. The colocalization of ER and CRF immunoreactivities was found in the MPOA and adjacent regions of the bed nucleus of the stria terminalis. In conclusion, the results of this study provide evidence that the MPOA may represent a potential site for the anorectic effects of E2. Furthermore, the presence of ER and CRF in neurons of the MPOA and adjacent areas suggests a direct interaction between estrogens and the CRF system in the MPOA that is consistent with a role for CRF in the anorectic effects of estrogens. Finally, the results of this study indicate that the effects of a CRF injection into the MPOA differ from those of estrogens, suggesting that if CRF neurons are involved in the anorectic effect of estrogens they likely exert their action outside the MPOA.
Carbohydrate versus fat intake: differing patterns of macronutrient selection in two inbred mouse strains
Authors: Smith B. K. , West D. B. , York D. A.
Published: December 2017

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.
Central vs. peripheral metabolic control of estrous cycles in Syrian hamsters. I. Lipoprivation
Authors: Schneider J. E. , Hall A. J. , Wade G. N.
Published: December 2017

Metabolic energy availability has profound effects on reproduction in a wide variety of species. We have been studying the effects of fasting on estrous cycles in Syrian hamsters as a model system for metabolic control of reproduction. In previous experiments, a 48-h period of fasting inhibited estrous cycles in lean, but not fat, hamsters. In fat hamsters the effects of fasting may have been offset by the presence of high circulating levels of free fatty acids mobilized from lipids in adipose tissue. Consistent with this idea fat hamsters treated with the inhibitor of fatty acid oxidation methyl palmoxirate (MP) showed fasting-induced anestrus. Experiment 1 was designed to examine whether vagally transmitted signals are critical for the inhibitory effects of fasting and MP treatment. Lean or fat hamsters that had received bilateral subdiaphragmatic vagotomy or sham surgery were fasted and treated with MP or vehicle. In vagotomized and sham-operated hamsters, estrous cycles were inhibited in lean fasted hamsters and in fat fasted hamsters treated with MP, but not in fat fasted hamsters treated with vehicle. Thus the results of experiment 1 indicated that vagally transmitted signals about peripheral fatty acid availability are not critical for the effects of these particular metabolic challenges on estrous cycles in Syrian hamsters. In experiment 2, hamsters without food were allowed to ingest pure glucose or fructose solutions or vegetable shortening. One-half of each group was treated with an inhibitor of glucose utilization, 2-deoxy-D-glucose (2-DG), or vehicle. If ingestion of fructose or shortening, but not glucose, had protected hamsters from 2-DG-induced anestrus, this might have indicated that peripheral fuel availability is critical for anestrus. On the contrary, 2-DG treatment induced anestrus regardless of the type of fuel ingested. Neither experiment yielded results that implicated changes in peripheral fuel availability as a critical signal in metabolic control of estrous cycles.
Depletion of linoleate induced by weight cycling is independent of extent of calorie restriction
Authors: Chen Z. Y. , Sea M. M. , Kwan K. Y. , Leung Y. H. , Leung P. F.
Published: December 2017

Recent epidemiological studies have suggested that weight cycling induced by repeated dieting over time may increase the risk of cardiovascular disease. It is speculated that the increased mortality from coronary heart disease for people with a history of excessive weight cycling could be attributed to change in lipid metabolism. Previous studies have demonstrated that repeated cycling of 100% food restriction followed by ad libitum refeeding caused a depletion of linoleate and alpha-linolenate in rats. The objective of the present study was to test the hypothesis that the weight cycling-induced reduction in linoleate and alpha-linolenate is independent of extent of calorie restriction. Two consecutive weight cycles in three experiments were induced by 100% calorie restriction, 60% calorie restriction, and 36% calorie restriction, respectively, followed by ad libitum refeeding. As the consequence of the two weight cycles, linoleate and linolenate were decreased, whereas myristate, palmitate, and palmitoleate were proportionally increased in carcass and adipose tissue lipids. The results of all three experiments showed a preferential depletion of linoleate and alpha-linolenate without changes in final body weight, total body fat, and adipose tissue pads in the weight-cycled rats. In addition, the triacylglycerol species profile in the adipose tissue of weight-cycled rats was significantly remodeled, with a proportional depletion of linoleate-enriched triacylglycerol species (LLL, LLO, and LLP, where L, O, and P are linoleic, oleic, and palmitic acid, respectively) and a proportional accumulation of palmitate-enriched triacylglycerol species (OPPo, PPPo, and PPP, where Po is palmitoleic acid). We conclude that weight cycling changes the ratio of polyunsaturated fatty acids to saturated fatty acids and remodels the adipose tissue triacylglycerol species profile in rats.
Increased net hepatic glucose output from gluconeogenic precursors after high-sucrose diet feeding in male rats
Authors: Pagliassotti M. J. , Prach P. A.
Published: December 2017

A high-sucrose diet reduces the ability of insulin to suppress hepatic glucose production (hepatic insulin resistance) in rats. The purpose of the present study was to investigate the contribution of hepatic gluconeogenesis to sucrose-induced hepatic insulin resistance. Single-pass liver perfusions were performed on 24-h food-deprived male Wistar rats after 8 wk on either a high-corn starch (ST; 68% of energy) or high-sucrose (SU; 68% of energy) diet. Hepatic glucose output (HGO, micromol of glucose x min(-1) x g(-1)) in the presence of lactate, alanine, or dihydroxyacetone (DHA) was used as an estimate of gluconeogenic capacity, because liver glycogen levels after the 24-h fast were negligible (<1.2 mg/g). HGO was significantly (P < 0.05) greater in SU vs. ST at all concentrations of lactate, alanine, and DHA. Maximal rates of HGO were 1.9 +/- 0.4 and 2.8 +/- 0.3 at 10 mM lactate, 0.6 +/- 0.2 and 1.4 +/- 0.3 at 10 mM alanine, and 1.7 +/- 0.3 and 2.6 +/- 0.2 at 20 mM DHA in ST and SU, respectively. When HGO was matched between SU and ST with the use of different precursor concentrations, there was a significant (P < 0.05) reduction in the ability of insulin (175 microU/ml) to suppress HGO in SU vs. ST. These data suggest that sucrose feeding increases gluconeogenesis from lactate, alanine, and DHA and that this route of glucose production is resistant to insulin suppression.
Interleukin-1 induces changes in sleep, brain temperature, and serotonergic metabolism
Authors: Gemma C. , Imeri L. , de Simoni M. G. , Mancia M.
Published: December 2017

Simultaneous recordings of sleep-wake activity and of serotonergic metabolism in the medial preoptic area were performed in freely moving rats after the intracerebroventricular injection of interleukin-1 (IL-1) at dark onset. IL-1 (2.5 ng) induced a biphasic increase in slow-wave sleep and an early increase in serotonergic metabolism starting 30 min postinjection. Phasic, state-specific changes (which have been described in spontaneous sleep) were superimposed on this tonic, overall increase in serotonergic metabolism. IL-1 (25 ng) induced an increase in wakefulness and a delayed increase in serotonergic metabolism, which started 120 min postinjection. This suggests that the time course of the serotonergic activation could play a role in mediating IL-1 effects on sleep. Both doses of IL-1 induced a similar and significant increase in brain cortical temperature, suggesting that IL-1 effects on sleep are not a secondary effect of the increase in cortical temperature and that the serotonergic system is not involved in IL-1-induced fever.
Partial lipectomy, but not PVN lesions, increases food hoarding by Siberian hamsters
Authors: Wood A. D. , Bartness T. J.
Published: December 2017

We tested the inverse relationship between body fat and food hoarding in Siberian hamsters by decreasing or increasing body fat through partial surgical lipectomy (LIPX) or by making obesity-inducing lesions of the paraventricular nucleus of the hypothalamus (PVNx), respectively. We asked three questions. 1) Is food hoarding increased after body fat loss due to LIPX? 2) Is food hoarding decreased after PVNx? 3) Does PVNx affect the hoarding response to LIPX? Hamsters housed in a simulated burrow system increased food hoarding after LIPX followed by a decrease to pre-LIPX levels as body fat was partially compensated through an increase in the mass of their unoperated fat pads. PVNx hamsters had increased body mass and food intake but did not have decreased food hoarding, nor was food hoarding increased by LIPX in PVNx hamsters. The partial body fat compensation by LIPX + PVNx hamsters suggests that the damaged PVN did not cause a general failure to sense energy deficits but did affect the ability to integrate internal and external energy stores.