bluuebunny/crossref_metadata_2025 huggingface dataset:
Acidic fibroblast growth factor activates hypothalamic-pituitary-adrenocortical axis in rats
Authors: Matsumoto Itsuro , Oomura Yutaka , Niijima Akira , Sasaki Kazuo , Aikawa Tadaomi
Published: December 2017

Effects of acidic fibroblast growth factor (aFGF), an endogenous satiety substance, on the hypothalamic-pituitary-adrenocortical axis were examined under pentobarbital sodium anesthesia in rats. A guide cannula was inserted into the cerebral third ventricle and a vascular indwelling catheter was inserted into the right atrium from the jugular vein 2 wk and 3 days, respectively, before the experiment. A marked dose-dependent increase in plasma corticosterone was detected from 20 min to 2 h after intracerebroventricular administration of aFGF (1–10 ng). Significant increases in plasma adrenocorticotropic hormone (ACTH) were observed from 5 to 150 min after the intracerebroventricular administration of 10 ng aFGF. Significant dose-dependent increases in plasma corticosterone were also observed after intravenous injections of aFGF (1, 10, and 100 ng), together with increases in the plasma ACTH level. Pretreatment with antibody to corticotropin-releasing factor via the intracerebroventricular route abolished the increases in corticosterone induced by intracerebroventricularly administered aFGF, but not those induced by intravenous injection of aFGF. In adrenal glands perfused in situ with artificial medium, the corticosterone secretion rate increased slightly in response to 10−9M aFGF. These findings suggest that intracerebroventricular administration of aFGF activates the hypothalamic-pituitary-adrenal axis via corticotropin-releasing factor release in the brain, whereas peripheral administration of aFGF activates adrenocortical secretion mainly via a direct action on ACTH release.
IGF-I stimulates protein synthesis but does not inhibit protein breakdown in muscle from septic rats
Authors: Hobler Scott C. , Williams Arthur B. , Fischer Josef E. , Hasselgren Per-Olof
Published: December 2017

Sepsis is associated with reduced protein synthesis and increased protein degradation in skeletal muscle. We examined the effects of insulin-like growth factor I (IGF-I) on protein synthesis and breakdown in muscles from nonseptic and septic rats. Sepsis was induced by cecal ligation and puncture; control rats were sham operated. Extensor digitorum longus muscles were incubated in the absence or presence of IGF-I at concentrations ranging from 100 ng/ml to 10 μg/ml. Total and myofibrillar protein breakdown rates were measured as net release of tyrosine and 3-methylhistidine, respectively. Protein synthesis was determined by measuring incorporation of [U-14C]phenylalanine into protein. IGF-I stimulated protein synthesis in a dose-dependent fashion in muscles from both sham-operated and septic rats, with a maximal effect seen at a hormone concentration between 500 and 1,000 ng/ml. IGF-I inhibited total and myofibrillar protein breakdown in muscles from sham-operated rats, whereas in muscles from septic rats, IGF-I had no effect on protein breakdown, even at high concentrations. The results suggest that protein breakdown in skeletal muscle becomes resistant to IGF-I during sepsis and that this resistance reflects a postreceptor defect.
Thermoeffector thresholds and preferred ambient temperatures of the FOK rat
Authors: Shido Osamu , Sakurada Sotaro , Sugimoto Naotoshi , Furuyama Fujiya , Nagasaka Tetsuo
Published: December 2017

The FOK is an inbred rat strain with a genotypic adaptation to hot environments. The present study compared the thermoeffector thresholds and preferred ambient temperatures (Tpref) of the FOK rat with those of other rat strains. Male FOK, WKAH, and Donryu rats were used. First, they were loosely restrained and placed individually in a metabolic chamber with an ambient temperature of 26.0°C. Their hypothalamic temperature (Thy), tail skin temperature (Tsk), and heat production ( M) were measured. After thermal equilibrium had been attained, the rats were gradually warmed and then cooled using an intravenous thermode. The threshold Thy values for tail skin vasodilation and cold-induced thermogenesis were defined as the points at which sharp increases in Tskand M occurred, respectively. The two thresholds of the FOK rat were lower than those of the WKAH and Donryu rats. In a second set of experiments, the FOK and WKAH rats were placed individually in a thermocline. Their intra-abdominal temperatures (Tab) were measured by a biotelemetry system, and the rats’ Tpref values were estimated with the thermal gradient. Mean Tab and Tpref over a 24-h period for the FOK rat were significantly lower than those of the WKAH rat. The results suggest that in the FOK rat the control ranges of autonomic and behavioral thermoregulation are lower than those of the other rat strains examined. This contributes to the maintenance of core temperature at low levels.
Temporal relationships between eating behavior and liver adenine nucleotides in rats treated with 2,5-AM
Authors: Koch James E. , Ji Hong , Osbakken Mary D. , Friedman Mark I.
Published: December 2017

Administration of the fructose analog 2,5-anhydro-d-mannitol (2,5-AM) elicits eating behavior in rats by its action in the liver. To evaluate whether the decrease in liver ATP levels produced by injection of 2,5-AM plays a role in the eating response, we examined the relationship between changes in eating behavior and liver adenine nucleotide levels over time in rats given 2,5-AM. Liver ATP concentrations decreased within 15 min after injection of 2,5-AM (300 mg/kg ip), remained low for up to 90 min postinjection, and returned to control (saline injection) levels by 4 h after treatment. Rats fed ad libitum initiated eating between 15 and 45 min after 2,5-AM treatment, after liver ATP levels had declined. Rats given food 1 h after 2,5-AM treatment increased food intake, but if access to food was delayed for 4 h after 2,5-AM injection the eating response was attenuated or absent. Whereas liver AMP and ADP levels were also altered by injection of 2,5-AM, changes in food intake did not consistently track changes in these nucleotides. The results support the hypothesis that the eating response to 2,5-AM is triggered by a decrease in liver ATP level.
TNF-α tolerance blocks LPS-induced hypophagia but LPS tolerance fails to prevent TNF-α-induced hypophagia
Authors: Porter M. H. , Arnold M. , Langhans W.
Published: December 2017

To investigate the role of tumor necrosis factor-α (TNF-α) in bacterial lipopolysaccharide (LPS)-induced hypophagia, we tested whether a cross tolerance between LPS and TNF-α exists with respect to their anorectic effects. Only the first of three subsequent intraperitoneal injections of LPS (100 μg/kg body wt) given every second day at dark onset (12:12-h light-dark cycle) led to a significant reduction of food intake in male rats. Likewise, intraperitoneal injections of human recombinant TNF-α (150 μg ≥ 3 × 106U/kg body wt) also resulted in tolerance to its hypophagic effect. LPS tolerance did not alter the hypophagic response to subsequently injected TNF-α ( n = 14). However, TNF-α pretreatment completely blocked the hypophagic response to LPS ( n = 14). The results demonstrate that tolerance to the hypophagic effect of exogenous TNF-α is sufficient to eliminate LPS-induced hypophagia. This is consistent with the hypothesis that endogenous TNF-α plays a major role in LPS-induced hypophagia. The ineffectiveness of LPS tolerance to attenuate TNF-α-induced hypophagia is compatible with findings demonstrating that reduced TNF-α production is an important feature of LPS tolerance.
Behavioral changes in fasting emperor penguins: evidence for a “refeeding signal” linked to a metabolic shift
Authors: Robin Jean-Patrice , Boucontet Laurent , Chillet Pascal , Groscolas René
Published: December 2017

This study examines the relationships between metabolic status and behavior in spontaneously fasting birds in the context of long-term regulation of body mass and feeding. Locomotor activity, escape behavior, display songs, body mass, and metabolic and endocrine status of captive male emperor penguins were recorded during a breeding fast. We also examined whether body mass at the end of the fast affected further survival. The major part of the fast ( phase II) was characterized by the maintenance of a very low level of locomotor activity, with almost no attempt to escape, by an almost constant rate of body mass loss, and by steady plasma levels of uric acid, β-hydroxybutyrate, and corticosterone. This indicates behavioral and metabolic adjustments directed toward sparing energy and body protein. Below a body mass of ∼24 kg ( phase III), spontaneous locomotor activity and attempts to escape increased by up to 8- and 15-fold, respectively, and display songs were resumed. This probably reflected an increase in the drive to refeed. Simultaneously, daily body mass loss and plasma levels of uric acid and corticosterone increased, whereas plasma levels of β-hydroxybutyrate decreased. Some experimental birds were seen again in following years. These findings suggest that at a threshold of body mass, a metabolic and endocrine shift, possibly related to a limited availability of fat stores, acts as a “refeeding signal” that improves the survival of penguins to fasting.
Regulation of the vasomotor activity of lymph microvessels by nitric oxide and prostaglandins
Authors: Mizuno Risuke , Koller Akos , Kaley Gabor
Published: December 2017

It was shown previously that the presence of endothelium modulates spontaneous vasomotion of small lymphatic vessels. In the present study, we aimed to elucidate the nature of endothelium-derived factors, produced in basal conditions and in response to agonists, that affect the smooth muscle tone of lymph microvessels in vitro. Afferent lymph microvessels were isolated from rat iliac lymph nodes, cannulated with glass micropipettes, and pressurized (6 cmH2O), and changes in their diameter were investigated with video microscopy. In resting conditions, isolated lymph vessels exhibited spontaneous constrictions and dilations. The maximum and minimum diameters ( D max and D min) were 149.8 ± 2.9 and 85.8 ± 3.6 μm, respectively. Acetylcholine (ACh, 10−7 to 10−5 M) and sodium nitroprusside (SNP, 10−8 to 10−6 M) temporarily abolished diameter oscillations, increasing the diameter of lymphatics dose dependently. For example, 10−5 M ACh and 10−6 M SNP increased the diameter ( D max) by 15.2 ± 2.2 and 25.0 ± 2.7 μm, respectively. Treatment of vessels with N G-nitro-l-arginine (10−4 M) significantly reduced the amplitude of diameter oscillations and nearly completely eliminated ACh-induced dilation of lymph microvessels, whereas SNP (10−6 M) elicited a significantly greater dilation (55.6 ± 7.5 μm). Arachidonic acid (AA, 10−8 to 10−6 M) constricted (up to 50 μm), whereas prostaglandin E2(PGE2, 10−9 to 10−7 M) dilated (up to 40 μm), lymphatic vessels. Indomethacin (10−5 M) increased both D max and D min and completely inhibited AA-induced constrictions, but did not affect PGE2-induced dilations of lymph microvessels. AA-induced constrictions of lymphatics were converted into dilations after treatment with SQ-29,548, a selective PGH2-thromboxane A2(PGH2-TxA2, 10−6 M) receptor antagonist, whereas PGE2-induced dilations were not affected. We conclude that endothelial nitric oxide and prostaglandins are important modulators of lymphatic vasomotion, hence pumping activity of lymph microvessels in vivo.
Menhaden oil prevents but does not reverse sucrose-induced insulin resistance in rats
Authors: Podolin Deborah A. , Gayles Ellis C. , Wei Yuren , Thresher Jeffrey S. , Pagliassotti Michael J.
Published: December 2017

Although fish oil supplementation may prevent the onset of diet-induced insulin resistance in rats, it appears to worsen glycemic control in humans with existing insulin resistance. In the present study, the euglycemic, hyperinsulinemic (4× basal) clamp technique with [3-3H]glucose and 2-deoxy-[1-14C]glucose was used to directly compare the ability of fish oil to prevent and reverse sucrose-induced insulin resistance. In study 1 (prevention study), male Wistar rats were fed a purified high-starch diet (68% of total energy), high-sucrose diet (68% of total energy), or high-sucrose diet in which 6% of the fat content was replaced by menhaden oil for 5 wk. In study 2 (reversal study), animals were fed the high-starch or high-sucrose diets for 5 wk and then the sucrose animals were assigned to one of the following groups for an additional 5 wk: high starch, high sucrose, or high sucrose with 6% menhaden oil. Rats fed the high-starch diet for 10 wk served as controls. In study 3 (2nd reversal study), animals followed a similar diet protocol as in study 2; however, the reversal period was extended to 15 wk. In study 1, the presence of the fish oil in the high-sucrose diet prevented the development of insulin resistance. Glucose infusion rates (GIR, mg ⋅ kg−1⋅ min−1) were 17.0 ± 0.9 in starch, 10.6 ± 1.7 in sucrose, and 15.1 ± 1.5 in sucrose with fish oil animals. However, in study 2, this same diet was unable to reverse sucrose-induced insulin resistance (GIR, 16.7 ± 1.4 in starch, 7.1 ± 1.5 in sucrose, and 4.8 ± 0.9 in sucrose with fish oil animals). Sucrose-induced insulin resistance was reversed in rats that were switched back to the starch diet (GIR, 18.6 ± 3.0). Results from study 3 were similar to those observed in study 2. In summary, fish oil was effective in preventing diet-induced insulin resistance but not able to reverse it. A preexisting insulin-resistant environment interferes with the positive effects of menhaden oil on insulin action.
Hormonally controlled chloride movement acrossDrosophilatubules is via ion channels in stellate cells
Authors: O’Donnell Michael J. , Rheault Mark R. , Davies Shireen A. , Rosay Phillipe , Harvey Brian J. , Maddrell Simon H. P. , Kaiser Kim , Dow Julian A. T.
Published: December 2017

Anion conductance across the Drosophila melanogaster Malpighian (renal) tubule was investigated by a combination of physiological and transgenic techniques. Patch-clamp recordings identified clusters of 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS)-sensitive “maxi-chloride” channels in a small domain of the apical membrane. Fluid secretion assays demonstrated sensitivity to the chloride channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid, diphenylamine-2-carboxylate, anthracene-9-carboxylic acid, and niflumic acid. Electrophysiological analysis showed that the calcium-mediated increase in anion conductance was blocked by the same agents. Vibrating probe analysis revealed a small number of current density hot spots, coincident with “stellate” cells, that were abolished by low-chloride saline or the same chloride channel blockers. GAL-4-targeted expression of an aequorin transgene revealed that the neurohormone leucokinin elicits a rapid increase in intracellular calcium levels in stellate cells that precedes the fastest demonstrable physiological effect. Taken together, these data show that leucokinins act on stellate cells through intracellular calcium to increase transcellular chloride conductance through channels. As electrogenic cation conductance is confined to principal cells, the two pathways are spatially segregated in this tissue.
Roles of cardiac output and peripheral resistance in mediating blood pressure response to stress in rats
Authors: Li Sheng-Gang , Randall David C. , Brown David R.
Published: December 2017

The change in arterial blood pressure (BP) in response to presentation of an acute behavioral stress (i.e., classical conditioning) in rat includes an initial rapid rise (C1) followed by a delayed, but more sustained, pressor response (C2). The purpose of this experiment is to determine the patterns of change in cardiac output (CO) and total peripheral vascular resistance (TPR) that are associated with the behaviorally induced pressor response. A blood flow probe was implanted around the ascending aorta, and a catheter was implanted in a femoral artery in 10 male Sprague-Dawley rats. The rats were trained by a 15-s tone (CS+) followed by a 0.5-s tail shock; another tone (CS−), never followed by shock, served as a behavioral control. BP responded to the stressful stimulus (CS+) by a rapid C1 increase (8 ± 1 mmHg; mean ± SE) followed by the delayed C2 response (2 ± 0.3 mmHg); the unconditioned response to shock was a 9 ± 2 mmHg increase in BP. The C1 BP increase produced a significant increase in TPR (10 ± 1 dyn ⋅ s/cm5); CO was not significantly changed. TPR decreased during C2 (−4 ± 2 dyn ⋅ s/cm5), whereas CO was significantly increased (2 ± 1 ml/min). These data contribute to our understanding of how the autonomic nervous system organizes the cardiovascular response to a suddenly perceived behavioral stress.
Phosphorylation of β-adrenergic receptor leads to its redistribution in rat heart during sepsis
Authors: Tang Chaoshu , Yang Jung , Wu Li-Ling , Dong Lin-Wang , Liu Maw-Shung
Published: December 2017

The role of receptor phosphorylation on the redistribution of β-adrenergic receptors (β-ARs) in rat hearts during different phases of sepsis was investigated. Sepsis was induced by cecal ligation and puncture (CLP). Changes in the distribution of β-ARs in the sarcolemmal and light vesicle fractions were studied using (−)-[4,6-propyl-3H]dihydroalprenolol ([3H]DHA). Phosphorylation of β-ARs was studied by perfusing hearts with [32P]H3PO4followed by identification of the phosphorylated β-ARs with immunoprecipitation using anti-β1-AR antibody. The results show that septic rat hearts exhibit an initial hypercardiodynamic (9 h after CLP; early sepsis) and a subsequent hypocardiodynamic (18 h after CLP; late sepsis) state. [3H]DHA binding studies show that, during early sepsis, the maximum binding capacity (Bmax) was increased by 26% in sarcolemma but was decreased by 30% in light vesicles, whereas, during late sepsis, the Bmaxwas decreased by 39% in sarcolemma but increased by 31% in light vesicles. These data indicate that β-ARs in the rat heart were externalized from light vesicles to sarcolemma during early sepsis but were internalized from surface membranes to intracellular sites during late sepsis. The immunoprecipitation studies reveal that the externalization of β-ARs during early sepsis was coupled with a concomitant decrease (−28.5 to −30.6%, P < 0.01) in the receptor phosphorylation, whereas the internalization of β-ARs during late sepsis was accompanied by a simultaneous increase (30.3 to 33.8%, P < 0.01) in the receptor phosphorylation. Because the phosphorylation/dephosphorylation of β1-ARs regulate their functional coupling and may reflect their subcellular distribution, it is suggested that the increase in receptor phosphorylation seen in late sepsis leads to the receptor internalization observed in late sepsis; similarly, externalization of (dephosphorylated) receptors in early sepsis may give rise to the apparent decrease in sarcolemmal receptor phosphorylation observed during this interval.
Effects of temperature on sleep in the developing rat
Authors: Morrissette Roger N. , Heller H. Craig
Published: December 2017

In altricial species, such as humans and rats, much of the development of autonomic systems occurs postnatally. Consequently, vulnerabilities exist early in postnatal development when immature autonomic functions are challenged by external factors such as variations in ambient temperature (Ta). Ta profoundly influences sleep/wake state structure in adult animals and humans, and exposure to excessive warmth has been implicated as a risk factor in sudden infant death syndrome. To better understand the relationship between temperature and sleep during development, we investigated the effect of Ta variation on sleep/wake state structure and sleep intensity in developing rats. In this experiment, sleep intensity was measured by the intensity of slow-wave activity during slow-wave sleep. Neonatal Long-Evans hooded rat pups were surgically prepared for chronic sleep/wake state and brain temperature (Tbr) recording. Two-hour recordings of sleep/wake state and Tbr were obtained from rats on postnatal day 12( P12), P14, P16, P18, and P20 at a Ta of either 28.0–30.0, 33.0–35.0, or 38.0–40.0°C. Ta significantly influenced sleep/wake state structure but had little, if any, effect on sleep intensity in developing rats.
Insulin-induced repartitioning of metabolic fuels inhibits hamster estrous behavior: role of area postrema
Authors: Panicker Anitha K. , Wade George N.
Published: December 2017

Excessive diversion of metabolic fuels away from oxidation and into adipose tissue storage depots, such as underfeeding or extraordinary levels of energy expenditure, can induce nutritional infertility. Treatment with pharmacological doses of insulin reduces metabolic fuel availability and suppresses both ovulatory cyclicity and pulsatile luteinizing hormone release in females of several mammalian species, but little attention has been paid to the effects of insulin treatments on reproductive behaviors. Ovariectomized Syrian hamsters were injected with long-acting insulin every 12 h for 72 h and were prevented from overeating by limiting their intake to ∼110% of pretreatment levels. When given estradiol and progesterone, insulin-treated hamsters exhibited significantly reduced levels of sexual receptivity compared with saline-treated controls. This insulin-induced inhibition of estrous behavior was prevented by lesions of the area postrema. Insulin treatments also caused changes in the number of detectable estrogen receptor immunoreactive cells in the hypothalamus and preoptic area. Therefore, insulin-induced repartitioning of metabolic fuels induces changes in estrous behavior and neural estrogen receptors that are indistinguishable from those caused by food deprivation, cold exposure, or treatment with metabolic inhibitors.
Renal neutral α-d-glucosidase has no role in transport ofd-glucose derived from maltose hydrolysis
Authors: Giudicelli Jean , Delque-Bayer Pascale , Sudaka Pierre , Poiree Jean-Claude
Published: December 2017

To reinvestigate the “hydrolase-related transport” concept, neutral α-d-glucosidase, a membrane-bound disaccharidase of renal proximal tubule, was first purified from brush-border membranes and then asymmetrically reincorporated into egg phosphatidylcholine vesicles. Proteolytic treatments and immunotitration studies demonstrated that this enzyme was integrated in native and artificial membrane vesicles with a similar topology. The uptake of free glucose and glucose produced by maltose hydrolysis was studied using 1) proteoliposomes containing integrated neutral α-d-glucosidase, in combination with other membrane proteins, and 2) proteoliposomes containing only the other membrane proteins but incubated in a medium containing neutral α-d-glucosidase in its hydrophilic form. No modification was observed in the uptake of freed-glucose or d-glucose produced by maltose hydrolysis, regardless of enzyme localization. In contrast to previous findings on the hydrolase-related transport concept, these results rule out any participation of neutral α-d-glucosidase in the transport of free glucose or glucose produced by maltose hydrolysis. Hydrolytic activity and transmembrane transport appear to be two independent and sequential steps.
Cerebral cortex does not modulate “regulated” decrease in core temperature during hypoxemia in rats
Authors: Rollins Evvi-Lynn M. , Fewell James E.
Published: December 2017

In newborns and adults of a number of species including humans, exposure to acute hypoxemia produces a “regulated” decease in core temperature, the mechanism of which is unknown. Considering that various cortical areas participate in autonomic regulation including thermoregulation, the present experiments were carried out to test the hypothesis that the cerebral cortex plays a role in modulating the regulated decrease in core temperature during acute hypoxemia. This hypothesis was tested by determining the core temperature response to acute hypoxemia in chronically instrumented adult Sprague-Dawley rats before and after cortical spreading depression (i.e., functional decortication) was produced by the local application of potassium chloride to the dura overlying the cerebral hemispheres. There was no effect of cortical spreading depression on baseline core temperature. Core temperature decreased during acute hypoxemia in a similar fashion when the cerebral cortex was intact as well as during functional decortication. Thus our data do not support the hypothesis that the cerebral cortex modulates the regulated decrease in core temperature that occurs in adult rats during acute hypoxemia.
Stanniocalcin in the seawater salmon: structure, function, and regulation
Authors: Wagner Graham F. , Jaworski Ewa M. , Haddad Michel
Published: December 2017

Stanniocalcin (STC) is a homodimeric glycoprotein hormone that was first discovered in fish, where it is produced by unique endocrine glands known as the corpuscles of Stannius (CS). In freshwater salmon, STC plays an integral role in Ca2+ and phosphate homeostasis. High levels of extracellular Ca2+promote the synthesis and release of STC, which on entering the bloodstream reduces the levels of gill and gut Ca2+ transport and renal phosphate excretion to restore normocalcemia. In this report, we have examined STC in seawater salmon. We have studied the distribution of STC protein and mRNA in marine Atlantic salmon CS cells, the responsiveness of these cells to Ca2+, and some physical properties of the hormone. Our results demonstrated that all Atlantic salmon CS cells expressed the STC gene. Furthermore, these cells exhibited a Ca2+ sensitivity that was remarkably similar to those in freshwater salmon in terms of its ability to stimulate STC secretion and gene expression. When Atlantic salmon glands were fractionated by concanavalin A (ConA)-Sepharose chromatography, two distinct forms of the hormone were identified, both of which were recognized by sockeye salmon STC antiserum, and designated as STC1 and STC2. STC1 was a glycosylated, 42-kDa disulfide-linked dimer, with a high affinity for ConA. STC2 did not bind to ConA, was 44 kDa in size, and had a different subunit structure. STC2 was also a less effective inhibitor of gill Ca2+ transport in fish. Collectively, the results suggest that there is a second form of STC in salmon.
Heterozygosity forLepoborLeprdbaffects body composition and leptin homeostasis in adult mice
Authors: Chung Wendy K. , Belfi Kristen , Chua Melvin , Wiley Jennifer , Mackintosh Ronald , Nicolson Margery , Boozer Carol N. , Leibel Rudolph L.
Published: December 2017

In an effort to understand the genetics of human obesity, we have studied the physiology and molecular genetics of rodent models with monogenetic forms of obesity including the leptin gene-defective ( Lepob/ Lepob) and leptin receptor gene-defective ( Leprdb/ Leprdb) mouse. In the experiments reported here, we investigated the effects of heterozygosity at Lepoband Leprdbon body composition and circulating leptin concentration in +/+, Leprdb/+, and Lepob/+ adult mice to identify possible gene dosage effects of these mutations that might elucidate their physiology. Adult mice heterozygous for the Lepobor Leprdballele had equivalent fat mass and percentage body fat, which was increased 27–47% and 23–35%, respectively, relative to +/+ littermates. Plasma leptin concentrations adjusted for fat mass were 6.5 ng/ml in the Lepob/+, 9.6 ng/ml in the +/+, and 11.5 ng/ml in the Leprdb/+ mice. Sex had no effect on plasma leptin after controlling for fat mass. These data, and data from a small number of mice heterozygous at both Lepoband Leprdb(compound heterozygotes), suggest that leptin protein produced per mass of body fat is reduced in Lepob/+ mice and that body fat is increased in Lepob/+ mice until plasma leptin concentrations reach that of a normal +/+ mouse. The elevated plasma leptin concentration in the Leprdb/+ mice suggests that LEPR may mediate autocrine suppression of Lep expression. These results raise the possibility that human mutations that have even subtle effects on the leptin/leptin receptor system in either the homozygous or heterozygous state may have significant effects on adiposity.
Tonic neurogenic inhibition of interleukin-6 secretion from murine spleen caused by opioidergic transmission
Authors: Straub Rainer H. , Dorner Monika , Riedel Jens , Kubitza Marion , Van Rooijen Nico , Lang Bernhard , Schölmerich Jürgen , Falk Werner
Published: December 2017

The peripheral nervous system and the immune system were shown to have neurohumoral interactions. This study extends observations that demonstrated neuronal modulation of spontaneous interleukin-6 (IL-6) secretion in the spleen by norepinephrine (NE) and β-endorphin. Spontaneous IL-6 secretion in vivo was markedly reduced by removal of macrophages with the clodronate technique. Furthermore, spontaneous IL-6 secretion was significantly inhibited at physiological concentrations of cortisol (10−7M). In the presence of 10−7M cortisol, addition of norepinephrine (NE; 10−5M) and isoproterenol (10−6and 10−5M) significantly increased spontaneous IL-6 secretion (+20%; P = 0.0280, P = 0.0005, and P = 0.0050, respectively). In contrast, addition of β-endorphin significantly inhibited spontaneous IL-6 secretion in the presence of 10−7M cortisol (−40%; 10−11M, P = 0.0410; 10−10M, P = 0.0005). To study the effect of endogenously released transmitters on spontaneous IL-6 secretion, spleen slices were electrically stimulated with 1, 5, 10, 50, and 100 Hz. Spontaneous IL-6 secretion was markedly reduced at a frequency of 10 Hz with 10−7M cortisol present ( P < 0.0001). This indicates that the combination of nerve firing at 5–10 Hz and physiological cortisol conditions inhibits spontaneous IL-6 secretion. Inhibition of spontaneous IL-6 secretion from spleen macrophages is most probably due to a net inhibitory effect of opioidergic transmission under these conditions.
Gelatinase B modulates selective opening of the blood-brain barrier during inflammation
Authors: Mun-Bryce Sheila , Rosenberg Gary A.
Published: December 2017

Matrix metalloproteinases (MMPs) are associated with neuroinflammatory diseases, and blood-brain barrier damage is a pathophysiological consequence of central nervous system inflammation. We examined whether an increase in MMP production is coupled with the breakdown of blood-brain barrier integrity in the lipopolysaccharide (LPS)-injured brain. Rat brain stimulated with LPS showed a significant rise in gelatinase B (MMP-9) production at 24 h compared with either tumor necrosis factor-α (TNF-α) or saline-injected controls. Latent 92-kDa gelatinase B was detected by 4 h, peaked at 8 h, and persisted for 24 h after LPS injection. Production of the active 84-kDa form of gelatinase B was less pronounced, but paralleled 92-kDa enzyme expression. Breakdown in blood-brain barrier integrity, measured by the infiltration of radiolabeled exogenous markers into the brain, was significant to [14C]sucrose (molecular mass 342 Da) and [14C]dextran (molecular mass 50–90 kDa) molecules in LPS-injected animals compared with saline-injected controls. The extent of MMP involvement in barrier permeability was examined in animals treated with the MMP inhibitor BB-1101. A significant drop in gelatinase A and B production was detected in LPS-injured animals receiving BB-1101 compared with untreated animals. This MMP inhibitor also reduced [14C]sucrose uptake in LPS-injected animals, but had no effect on [14C]dextran uptake. MMP production is upregulated in LPS-injured brain tissue and is instrumental in regulating the size-differentiated opening of the blood-brain barrier during acute neuroinflammation.
Rat trehalase: cDNA cloning and mRNA expression in adult rat tissues and during intestinal ontogeny
Authors: Oesterreicher Thomas J. , Nanthakumar Nanda N. , Winston John H. , Henning Susan J.
Published: December 2017

A partial rat trehalase cDNA has been cloned and used to examine trehalase mRNA expression. Northern blotting with total RNA from 11 adult rat tissues showed a trehalase transcript only in small intestine, where it was abundant in proximal regions but declined steeply toward the ileum. During development, trehalase mRNA was not detectable in jejunum until postnatal day 19 and then increased markedly through day 25. Modest levels of trehalase mRNA were induced precociously by administration of dexamethasone, with increasing responsiveness evident between the first and second postnatal weeks. In contrast, analysis of sucrase-isomaltase mRNA on the same blots showed maximal induction at both ages. In adrenalectomized animals, the ontogenic increase of trehalase mRNA began as usual but proceeded more slowly than in control animals. Overall, trehalase mRNA expression in the rat displayed both similarities and differences compared with rabbit. Moreover, the differences revealed in glucocorticoid responsiveness of trehalase mRNA and sucrase-isomaltase mRNA suggest that the actions of these hormones on the developing intestine may be more complex than previously recognized.
Effect of renal interstitial adenosine infusion on phosphate excretion in diabetes mellitus rats
Authors: Pflueger Axel C. , Berndt Theresa J. , Knox Franklyn G.
Published: December 2017

We previously demonstrated an increased sensitivity of the renal vasculature to adenosine (ADO) mediated via ADO A1receptors in streptozotocin (STZ) diabetic rats. Because ADO stimulates Pireabsorption in the proximal tubule, the present study was performed to determine whether the sensitivity of the renal tubular system to the antiphosphaturic effect of ADO is enhanced in STZ rats. Clearance studies were performed, and ADO was infused into the renal interstitium via implanted matrices in STZ- and control (Con) rats to mimic the effects of endogenous ADO. Renal phosphate excretion was significantly increased in STZ rats (0.75 ± 0.05 μmol/24 h) compared with Con rats (0.35 ± 0.08 μmol/24 h), and fractional phosphate excretion ([Formula: see text]) tended to be higher in STZ rats (34.8 ± 4.1%) than in Con rats (26.7 ± 2.2%). Renal interstitial ADO infusion (5 μmol/h) was significantly more antiphosphaturic in STZ rats ([Formula: see text] decreased by 6.95 ± 1.36%; P < 0.05) than in Con rats ([Formula: see text] decreased by 2.90 ± 1.6%; P > 0.05), in which ADO only tended to decrease[Formula: see text]. To determine the role of ADO A1receptors on Piexcretion, the selective ADO A1receptor blocker 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was infused into the renal interstitium. DPCPX increased[Formula: see text] by 4.3 ± 1.2% ( P < 0.05) in the presence and 7.1 ± 3.9% ( P < 0.05) in the absence of ADO infusion in Con rats but had no effect on[Formula: see text] in STZ rats. In conclusion, STZ-diabetes mellitus enhances the antiphosphaturic effect of ADO by mechanisms unrelated to ADO A1receptor stimulation.
Insulin increases fatty acid synthase gene transcription in human adipocytes
Authors: Claycombe Kate J. , Jones Brynn H. , Standridge Melissa K. , Guo Yingshi , Chun Joseph T. , Taylor James W. , Moustaïd-Moussa Naïma
Published: December 2017

The purpose of this study was to investigate the molecular mechanism whereby insulin increases expression of a key de novo lipogenic gene, fatty acid synthase ( FAS), in cultured human adipocytes and hepatoma cells. RNA isolated from cultured adipocytes or from Hep G2 cells treated with or without insulin (20 nM) was analyzed. In addition, run-on transcription assays and measurements of RNA half-life were performed to determine the controlled step in FAS gene regulation by insulin. We demonstrated that FAS mRNA was expressed in both Hep G2 cells and human adipocytes. Insulin induced an approximately five- and threefold increase in FAS mRNA content in adipocytes and hepatoma cells, respectively. Similar regulation of FAS was observed in adipocytes from lean and obese human subjects. Furthermore, we demonstrated that the induction of human FAS expression by insulin was due to increased transcription rate of the FAS gene in human adipocytes, whereas mRNA stabilization accounted for increased FAS mRNA content in hepatoma cells. In conclusion, we report here for the first time expression of human FAS mRNA and its specific transcriptional induction by insulin in cultured human adipocytes.
Changes in extracellular serotonin in rat hypothalamus affect thermoregulatory function
Authors: Lin M. T. , Tsay H. J. , Su W. H. , Chueh F. Y.
Published: December 2017

Experiments were carried out to determine the effects of altering the serotonin (5-HT) levels in the hypothalamus on thermoregulatory function in unanesthetized restrained rats. Local perfusion of the hypothalamus with dialysis solution containing 5-hydroxytryptophan (a 5-HT precursor), fluoxetine (a 5-HT reuptake inhibitor), or high potassium significantly increased both colonic temperature (Tco) and the extracellular concentrations of 5-HT in the hypothalamus. Reciprocally, both extracellular concentration of 5-HT in the hypothalamus and Tco were decreased with a dialysis solution containing tetrodotoxin (which blocks the voltage-dependent sodium channel), zero calcium concentration, or systemic administration of 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT, 5-HT1Aagonist). Intrahypothalamic administration of 8-OH-DPAT and (2,5-dimethoxy-4-iodophenyl)-2-aminopropane (a 5-HT2 agonist) produced hypothermic and hyperthermic effects, respectively. The results indicate that elevating the 5-HT levels in the hypothalamus activates postsynaptic 5-HT2 receptors and results in hyperthermic effects, whereas stimulation of presynaptic 5-HT1A receptors in the hypothalamus reduces the endogenous 5-HT release and results in hypothermic effects.
Hypothalamic-pituitary-adrenal axis changes allow seasonal modulation of corticosterone in a bird
Authors: Romero L. Michael , Soma Kiran K. , Wingfield John C.
Published: December 2017

We examined possible mechanisms underlying seasonal stress modulation in Lapland longspurs ( Calcarius lapponicus), a species that breeds and molts (the energetically costly replacement of feathers) in the Alaskan Arctic. Free-living Lapland longspurs show dramatically reduced maximal corticosterone release during molt compared with the breeding season, an effect lost in captive birds. Neither changes in corticosterone binding proteins nor the overall condition of the bird (assessed by weight and fat storage) can explain different seasonal corticosterone responses. Adrenal insensitivity also does not fully explain reduced maximal output because exogenous ACTH enhanced corticosterone release during molt. Exogenous ACTH in molting birds, however, cannot stimulate corticosterone to stress-induced levels during breeding, implying reduced adrenal capacity. Lapland longspur pituitaries appeared to respond to exogenous corticotropin-releasing factor, arginine vasotocin, and mesotocin (the avian equivalents of arginine vasopressin and oxytocin) during molt, suggesting that a mechanism upstream of the pituitary blunts corticosterone release. Taken together, these results indicate that seasonal modulation of corticosterone release in this species is controlled at multiple sites in the hypothalamic-pituitary-adrenal axis.
Evidence for a low-affinity, high-capacity uniport for amino acids inBombyx morilarval midgut
Authors: Leonardi M. G. , Casartelli M. , Parenti P. , Giordana B.
Published: December 2017

We investigated the kinetics of leucine influx as a funtion of external substrate concentration between 0.03 and 16 mM in brush-border membrane vesicles (BBMV) prepared from the middle region of Bombyx mori larval midgut. A detailed kinetic analysis of leucine uptake led to the identification, in parallel with the K+-dependent symporter for neutral amino acids, of a K+-independent, low-affinity, high-capacity system. The parameter values of the Michaelis constant (7.12 mM) and maximal rate of transport (4.48 nmol ⋅ 7 s−1⋅ mg protein−1) were not influenced by an external alkaline pH nor by a transmembrane electrical potential difference. The uniporter is poorly specific, as it displayed the following rank of preference: Leu, His, Val, Ile, Phe, Ser > Lys, Arg, Gln > Pro, 2-amino-2-norbornane-carboxylic acid, Ala, Gly. The kinetic analysis performed in BBMV prepared from the posterior midgut portion indicates that the low-affinity, high-capacity uniporter is present along the entire length of the silkworm larval midgut with similar expression and functional properties.
Mitochondrial oxidative phosphorylation thermodynamic efficiencies reflect physiological organ roles
Authors: Cairns Charles B. , Walther James , Harken Alden H. , Banerjee Anirban
Published: December 2017

Mitochondria cannot maximize energy production, efficiency, and the cellular ATP phosphorylation potential all at the same time. The theoretical and observed determinations of coupling of oxidative phosphorylation in mitochondria from rat liver, heart, and brain were compared using classical and nonequilibrium thermodynamic measures. Additionally, the optimal thermodynamic efficiency and flow ratios were determined for control of the two energy-converting complexes of the respiratory chain: complex I (NADH), which reflects the integrated cellular pathway, and complex II (FADH2), the predominantly tricarboxylic acid (TCA) cycle pathway. For all three organs, the cellular respiratory pathway was more tightly coupled than the TCA pathway and resulted in a greater optimal efficiency. Liver mitochondria are the most thermodynamically efficient at ATP production using oxidative phosphorylation. Heart and brain mitochondrial systems utilize more oxygen, but can produce ATP at a faster rate than liver systems. Per the theory of economic degrees of coupling, isolated rat liver mitochondrial systems are designed for the economic production of ATP for use in cellular processes. In the brain, the mitochondrial TCA cycle pathway promotes the maximal maintenance of the cellular energy state for cellular viability, whereas in the heart the TCA cycle pathway maximizes the production of ATP. The coupling of oxidative phosphorylation not only can be expected to change with substrate availability but may also reflect an ontogenetic response of mitochondria to fit specific organ roles in the rat.
Role of the insular cortex in the modulation of baroreflex sensitivity
Authors: Saleh Tarek M. , Connell Barry J.
Published: December 2017

Cervical vagal stimulation for 2 h results in a depressed baroreflex sensitivity produced by an enhanced sympathetic output, as indicated by increased plasma norepinephrine levels. The current study examined the role of the insular cortex in modulating the vagal stimulation-induced changes in baroreflex sensitivity. Male Sprague-Dawley rats were anesthetized with thiobutabarbitol sodium and instrumented for recording blood pressure, heart rate, intravenous drug administration, and vagal afferent nerve stimulation. Stereotaxic microinjections (300 nl) of either 5% lidocaine or 0.9% saline were made bilaterally into the insula. Thirty minutes after 2 h of vagal stimulation, the baroreflex was significantly depressed and plasma norepinephrine levels were significantly elevated in both groups. The baroreflex was also significantly depressed after bilateral lidocaine injections into the insula, independent of vagal stimulation. However, no significant change in plasma norepinephrine was observed, suggesting that an attenuated parasympathetic output contributed to the altered baroreflex. Taken together, the results suggest that the insular cortex modulates the cardiac baroreflex through a modulation of parasympathetic output.
Qualitative regional differences in adipose tissue growth and cellularity in male Wistar rats fed ad libitum
Authors: DiGirolamo M. , Fine J. B. , Tagra K. , Rossmanith R.
Published: December 2017

Adipose tissue grows primarily by a combination of increases in fat cell volume (hypertrophy) and in fat cell number (hyperplasia), but the regional growth pattern of white adipose tissue depots in animal species and in the human is still unclear. In this study we characterized fully the age-related changes in adipose tissue growth, composition, and cellularity of four fat depots of male Wistar rats that varied in age from 7 wk to 15 mo and in body weight from 178 to 808 g. Body weight and the weight of each of the four adipose depots studied (epididymal, mesenteric, subcutaneous inguinal, and retroperitoneal) increased progressively with age and ad libitum feeding. Comparison of the cellularity of the four adipose depots, however, showed remarkable and significant differences in the pattern of growth within the same animals. The cumulative growth of the two intra-abdominal fat depots (mesenteric and epididymal) was due mostly to hypertrophy (increases in cell volume of 83 and 64%, respectively), whereas the growth of the other two depots (retroperitoneal and inguinal) was due predominantly to hyperplasia (increases in cell number of 58 and 65%, respectively). These findings uncover major and unexpected regional differences in the modulation of adipose tissue growth within aging animals fed ad libitum and suggest local, region-specific regulatory controls of this growth.
Neurophysiological modeling of voiding in rats: urethral nerve response to urethral pressure and flow
Authors: Le Feber Joost , Van Asselt Els , Van Mastrigt Ron
Published: December 2017

In male urethan-anesthetized rats, activity was measured in nerves that run over the proximal urethra. The urethral nerve response to stepwise urethral perfusion could be described by a four-parameter model (fit error <6%). At the onset of perfusion, the urethra was closed and the pressure increased with the infused volume. The nerve activity (NA) increased linearly with this inserted volume to a maximum (NAmax), which was proportional to the instantaneous pressure. The duration of this first episode (δ t) was inversely proportional to the perfusion rate. After infusion of a fixed volume, the urethra opened and the NA decreased with a time constant ϕ−1 (∼1.8 s) to an elevated level (NAlevel). NAlevel was linearly related to the steady-state pressure. Accordingly, sensors in the urethra are sensitive to pressure rather than to the perfusion rate. The parameters NAmax, NAlevel, and δ t showed very good reproducibility (SD ∼19% of mean). The measured activity was most likely afferent and conducted to the major pelvic ganglion.
Electrical potential difference between exocelomic fluid and maternal blood in early pregnancy
Authors: Ward Stuart , Jauniaux Eric , Shannon Claire , Rodeck Charles , Boyd Robert , Sibley Colin
Published: December 2017

The forces that drive transfer of solutes between maternal blood and embryo in early human pregnancy are poorly understood. The aim of this study was to determine whether there is an electrical potential difference (PD) between maternal blood and the exocelomic cavity and between maternal blood and the amniotic cavity in the normal human conceptus at or before 10 wk of pregnancy. We measured PD between a saline-filled catheter in a forearm vein of women undergoing termination of pregnancy for psychological reasons in the first trimester and a second saline-filled catheter in the exocelomic cavity or amniotic cavity of their conceptus. The mean (±SE) maternal blood/exocelomic cavity PD in eight women was 8.7 ± 1.0 mV and the mean maternal blood/amniotic cavity PD in four of the women was 6.7 ± 1.3 mV, embryo side negative for both sets of measurement. These data show that there is a PD between maternal and embryonic extracellular fluid in the first trimester that will directly influence exchange of ions between the two compartments.