bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated infusions of TNF-alpha cause attenuation of the thermal response and influence LPS fever in guinea pigs
Authors: Goldbach J. M. , Roth J. , Storr B. , Zeisberger E.
Published: December 2017

In conscious, freely moving guinea pigs, tumor necrosis factor (TNF)-alpha and TNF-beta, infused into the aortic arch within a period of 45 min at a dosage of 5 micrograms/kg, induced different thermal responses. TNF-alpha evoked a biphasic elevation of abdominal temperature, both phases together lasting longer than 6 h. In response to infusions of TNF-beta, the first phase, lasting approximately 120 min, was the same as was observed in response to TNF-alpha, whereas the longer second phase of temperature increase was missing. When the infusion of TNF-alpha was repeated four times at intervals of 3 days, the second phase of the increase in abdominal temperature (120-360 min after start of infusion) tended to decrease in response to the third and was significantly attenuated in response to the fourth infusion of TNF-alpha. A control group of guinea pigs received four infusions of solvent (0.9% sterile pyrogen-free saline). Another 3 days after the fourth infusion of TNF-alpha or solvent, all animals were injected with 20 micrograms/kg bacterial lipopolysaccharide (LPS from Escherichia coli; intramuscular injection). In those guinea pigs having developed a reduced responsiveness to TNF-alpha, the first phase of LPS-induced fever was significantly suppressed, whereas the second phase tended to be enhanced, compared with animals having received four infusions of solvent. In conclusion, guinea pigs develop a reduced responsiveness to TNF-alpha after its repeated administration. In the state of lower reactivity to exogenous TNF-alpha, a reduced response of the first phase of LPS-induced fever (during which endogenous TNF-alpha is released) can be observed. This indicates that endogenous TNF-alpha may contribute to LPS-induced fever only in the initial phase of the febrile response of guinea pigs.
Perinatal expression of adenylyl cyclase subtypes in rat brown adipose tissue
Authors: Chaudhry A. , Muffler L. A. , Yao R. , Granneman J. G.
Published: December 2017

The ability of norepinephrine to stimulate adenylyl cyclase (AC) activity increases during the perinatal period in rat brown adipose tissue (BAT), and this increase is associated with changes in the activities of both GS alpha and AC. The purpose of this study was to determine which AC subtypes are present in neonatal BAT and to examine whether the perinatal increase in AC activity corresponds to an increase in the expression of a particular AC subtype. Analysis of AC mRNAs by nuclease protection assay demonstrated the presence of mRNAs encoding AC-III, AC-IV, AC-VI, and AC-IX in embryonic and postnatal BAT. Of the subtypes detected, only AC-III mRNA levels increased substantially during the perinatal period. The increase in AC-III expression was paralleled by an increase in isoproterenol-stimulated AC activity. Treatment of neonates was the sympathetic neurotoxin 6-hydroxydopamine abolished the perinatal increase in both AC activity and AC-III mRNA levels but had no effect on the expression of other AC subtypes. These results strongly indicate that the increase in AC activity during the perinatal period is due to an increase in the expression of AC-III.
Does ingested fat produce satiety?
Authors: Horn C. C. , Tordoff M. G. , Friedman M. I.
Published: December 2017

Administration of fat directly into the gastrointestinal tract of rats produces a rapid and often substantial reduction of feeding behavior. This contrasts with the normal consumption of a fat meal, which produces little change in subsequent food intake. To determine whether procedural differences account for this discrepancy, we examined the satiating effect of ingested fat on food intake of rats maintained under feeding conditions similar to those employed in studies involving gastrointestinal delivery of fat (i.e., food deprivation, liquid diet). Ingestion of approximately 1.5 ml corn oil had no effect on subsequent liquid diet intake until 90 min after oil ingestion. When rats ingested oil 4 h before access to the liquid diet, to allow time for additional gastrointestinal clearance, liquid diet intake was reduced by 13% in the first 30 min of access. These findings indicate that ingested fat decreases short-term intake slightly, but only if time is allowed for postabsorptive delivery. The results question the physiological significance of the marked suppression of food intake observed in response to administration of fat directly into the gastrointestinal tract.
Effect of high FFA on glycogenolysis in oxidative rat hindlimb muscles during twitch stimulation
Authors: Dyck D. J. , Peters S. J. , Wendling P. S. , Spriet L. L.
Published: December 2017

The effect of elevated free fatty acids (FFA) on carbohydrate (CHO) utilization in the oxidative muscles of the isolated hindlimb was determined using twitch contraction paradigms evoking a wide range of O2 uptakes and glycogenolysis. The hindlimb was perfused with either 0 or 1.8 mM FFA for 10 min at rest and then subjected to 20 min of stimulation at 0.4, 0.7, 1, 2, 3, or 4 Hz. Soleus (Sol), plantaris (Pl), and red gastrocnemius (RG) were sampled after rest perfusion or stimulation. FFA had little effect on glycogenolysis during stimulation, although glycogen sparing occurred with one of the lesser intensity protocols in each muscle (Sol, 0.4 Hz; RG, 0.7 Hz; Pl, 1 Hz). Muscle citrate and acetyl-CoA were elevated in Sol during several stimulation protocols with high FFA, but this effect was inconsistent in Pl and RG. The sparing of glycogen, when it did occur, was generally unrelated to increases in either citrate or acetyl-CoA content. Furthermore, protocols in which citrate or acetyl-CoA were elevated in the presence of elevated FFA did not demonstrate glycogen sparing. Hindlimb lactate efflux at rest was reduced with FFA but unaffected during stimulation. Glucose uptake was unaffected by FFA at rest and during stimulation protocols, except 3 Hz. The present study does not support the classically proposed roles of citrate and acetyl-CoA in the FFA-induced downregulation of CHO utilization in electrically stimulated rat skeletal muscle.
Adipose-specific overexpression of GLUT-4 in transgenic mice alters lipoprotein lipase activity
Authors: Gnudi L. , Jensen D. R. , Tozzo E. , Eckel R. H. , Kahn B. B.
Published: December 2017

Transgenic mice overexpressing GLUT-4 selectively in adipose tissue using the aP2 promoter/enhancer develop obesity, enhanced glucose tolerance, and increased insulin sensitivity. The current study was designed to determine whether altering glucose transport affects lipoprotein lipase (LPL) activity. Female transgenic mice (10-12 mo old) have increased parametrial fat pad weight, adipocyte size, total body lipid and fasting plasma triglycerides, fatty acids, and glycerol compared with nontransgenics. Stimulation of LPL activity by feeding is blunted in parametrial and perirenal fat from 15- and 22-fold in nontransgenic mice to three- to sevenfold in transgenics. LPL activity in the fed state in transgenic mice is reduced 60-75% in fat. In heart and skeletal muscle of transgenic mice, LPL activity in the fasted state is 55-65% lower than in nontransgenics and feeding induces an unexpected rise in LPL activity. Muscle LPL activity is strongly and inversely correlated with glucose transport in adipocytes (r = -0.942, P < 0.005), which is increased 15- to 27-fold in the basal state and 4.5- to 6.9-fold in the insulin-stimulated state in transgenics. Whereas stimulation of adipose LPL may be blunted by lower plasma insulin levels in transgenics, fasting muscle LPL may be suppressed by elevated plasma lipids. Thus altering the partitioning of glucose between adipose tissue and muscle alters a critical step for the partitioning of lipoprotein fatty acids between these tissues.
Potassium conductance activated during regulatory volume decrease by mudpuppy red blood cells
Authors: Bergeron L. J. , Stever A. J. , Light D. B.
Published: December 2017

The cellular basis of regulatory volume decrease (RVD) by mudpuppy (Necturus maculosus) red blood cells (RBCs) was examined. Volume regulation was inhibited by replacing extracellular Na+ with K+. In contrast, addition of gramicidin (5 microM) to the extracellular medium enhanced RVD. The K(+)-channel blocker quinine (1 mM) also inhibited RVD, and this inhibition was reversed by gramicidin (5 microM). In addition, a 0 Ca(2+)-EGTA Ringer blocked RVD, whereas the Ca2+ ionophore A23187 ( microM) enhanced recovery of cell volume. The stretch-activated ion channel antagonist gadolinium (10 microM) inhibited RVD, and this effect was reversed by A23187 (2 microM). Furthermore, the calmodulin inhibitors pimozide (10 microM) and N-(6-aminohexyl)-5-chloro-1-napthalene-sulfonamide (0.1 mM) blocked RVD, and this inhibition was reversed with gramicidin (5 microM). Consistent with these findings, a K(+)-selective membrane conductance was activated by exposing RBCs to a 0.5x Ringer solution (observed with the whole cell patch clamp technique). This conductance was inhibited by quinine (1 mM), gadolinium (10 microM), and pimozide (10 microM). These results indicate that cell swelling activates a K+ conductance by a Ca(2+)-calmodulin-dependent mechanism and that this channel mediates K+ loss during RVD.
Metabolic fate of an oral tracer dose of [13C]docosahexaenoic acid triglycerides in the rat
Authors: Brossard N. , Croset M. , Lecerf J. , Pachiaudi C. , Normand S. , Chirouze V. , Macovschi O. , Riou J. P. , Tayot J. L. , Lagarde M.
Published: December 2017

The appearance of 13C in rat lipoprotein, blood cells, and brain lipids was followed as a function of time after the ingestion of triglycerides (TG) containing [13C]22:6n-3. The time course of 13C abundance in 22:6n-3 of various lipid pools, measured by gas chromatography combustion-isotope mass spectrometry, established precursor-product relationships within lipids. The [13C]22:6n-3 was rapidly incorporated into very low density lipoprotein-chylomicron-TG and unesterified fatty acids bound to albumin, with a concomitant maximal appearance at 3 h and further decline. Lysophosphatidylcholines (lysoPC) bound to albumin were also enriched in [13C]22:6n-3, and their labeling appeared to be mainly due to hepatic secretion at the earliest time points. From 12 h postingestion, the synthesis of [13C]22:6n-3-lysoPC was twice as high as that of unesterified [13C]22:6n-3, making lysoPC a potential source of 22:6n-3 supply for tissues. The labeling of platelets, red blood cells, and brain phospholipids presented different kinetics, presumably involving the two lipid forms of [13C]22:6n-3 bound to albumin, to different extents. We conclude that [13C]22:6n-3 esterified in TG is rapidly redistributed within blood lipoproteins and the albumin fraction and that its incorporation in lipid species bound to albumin influences its uptake by target tissues.
Ultradian rhythms of autonomic, cardiovascular, and neuroendocrine systems are related in humans
Authors: Shannahoff-Khalsa D. S. , Kennedy B. , Yates F. E. , Ziegler M. G.
Published: December 2017

Autonomic, cardiovascular, and neuroendocrine activities were monitored for 5-6 h in 10 normal adult resting humans (8 males, 2 females). The nasal cycle, a measure of lateralized autonomic tone, was measured at 4 Hz. Impedance cardiography (BoMed NCCOM3) was used to measure cardiac output, thoracic fluid index, heart rate, ejection velocity index, stroke volume, and ventricular ejection time (averages of 12 heart beats). Systolic, diastolic, and mean arterial pressures were measured with an automated cuff at 7.5-min intervals. Separate blood samples were taken every 7.5 min simultaneously from both arms with the use of indwelling venous catheters. Assays for adrenocorticotropic hormone, luteinizing hormone, norepinephrine, epinephrine, and dopamine were performed on samples from each arm. Time-series analysis, using the fast orthogonal search method of Korenberg, was used to detect variance structure. Significant spectral periods were observed in five windows at 220-340, 170-215, 115-145, 70-100, and 40-65 min. The greatest spectral power was observed in the lower frequencies, but periods at 115-145, 70-100, and 40-65 min were common across variables. Significant correlation coefficients for linear regressions of all paired variables in each subject were observed in 38.87% of the comparisons (subject range, 18.05-48-9.70%) with r > 0.30. These results suggest that either a common oscillator (the hypothalamus) or mutually entrained oscillators regulate these systems.
Integration of vascular, contractile and metabolic responses to hypoxia: effects of maturation and adenosine
Authors: Matherne G. P. , Berr S. S. , Headrick J. P.
Published: December 2017

We examined myocardial responses to reduced arterial PO2 and the role of endogenous adenosine in constant-pressure perfused hearts from immature (Imm) and mature (Mat) rabbits. During normoxia, coronary flow and myocardial O2 consumption were similar in both groups. With moderate hypoxia, coronary perfusate flow increased by 125 +/- 16% in Imm but by only 68 +/- 12% in Mat hearts. Imm hearts displayed better maintenance of contractile function (87 vs. 67% in Mat hearts) and metabolic state. Blockade of cardiac adenosine receptors with 25 microM 8-p-sulfophenyltheophylline attenuated vasodilation during hypoxia, reduced contractile function, and abolished age-related differences in one response to hypoxia. Myocardial purine release and extracellular purine levels were threefold higher in Mat compared with Imm hearts and was associated with higher cytosolic 5'-AMP concentration (and lower [ATP]/[ADP].[P(i)], where [ATP], [ADP], and [P(i)] are concentrations of ATP, ADP and P(i), respectively) in Mat hearts. In summary, 1) Imm hearts are functionally and metabolically more tolerant of hypoxic perfusion, largely because of improved hypoxia-induced coronary vasodilation; 2) endogenous adenosine mediates this beneficial vasodilation, enhancing hypoxic tolerance; and 3) improved vascular sensitivity to adenosine allows for enhanced vasodilatory responses in the face of lower adenosine levels and higher energy state in immature hearts.
Capsaicin attenuates feeding suppression but not reinforcement by intestinal nutrients
Authors: Lucas F. , Sclafani A.
Published: December 2017

During and after a meal, the presence of nutrients in the intestine can be rapidly detected and signaled to the brain via visceral afferents. Intestinal infusions of carbohydrate and fat suppress food intake, and this satiety action is inhibited by capsaicin, a neurotoxin that produces a partial visceral deafferentation. This study determined if the postingestive reinforcing action of nutrients is also suppressed by capsaicin treatment. Food-restricted control and capsaicin-treated rats were trained to drink a flavored solution paired with intraduodenal infusions of carbohydrate (Polycose solution) on some days and, on other days, a differently flavored solution paired with intraduodenal water infusions. In a choice test, both groups displayed a strong preference for the Polycose-paired flavor. In a subsequent satiety test, however, intraduodenal Polycose suppressed sucrose sham feeding in the controls but not in capsaicin-treated rats. The same rats were next trained to associate new flavors with intraduodenal fat (corn oil emulsion) and intraduodenal water infusions. During training, oil infusions reduced oral intakes in the controls much more than in the capsaicin-treated rats. Both groups reliably preferred the oil-paired flavor in the subsequent choice test. These results indicate that, unlike the satiating effect of intestinal carbohydrate and fat, the reinforcing actions of these nutrients are not mediated by capsaicin-sensitive visceral afferents. The data also imply that the postingestive reinforcement produced by nutrients is not dependent on the nutrients' satiating quality.
Rapid elicitation of salt appetite by an intravenous infusion of angiotensin II in rats
Authors: Fitts D. A. , Thunhorst R. L.
Published: December 2017

A role for the renal renin-angiotensin system in the direct stimulation of salt appetite in the rat remains controversial because attempts to elicit the behavior by intravenous administration of angiotensin II (ANG II) have been unconvincing. We recently demonstrated that depletion-induced salt appetite was attenuated by selective blockade of peripheral ANG II synthesis with an intravenous dose of converting enzyme inhibitor [captopril (Cap)] that does not block the synthesis of ANG II inside the blood brain barrier. We now show that intravenous ANG II at 30 ng/min rapidly reestablishes salt appetite in Cap-blocked rats. The mean arterial blood pressure (MAP) of unblocked, sodium-depleted rats was normal, but Cap-blocked, depleted rats had low MAP. An intravenous infusion of ANG II in Cap-blocked rats brought MAP into the normal range and elicited water and salt drinking within 90 min. Phenylephrine also normalized MAP but failed to elicit fluid intake in Cap-blocked, sodium-deficient rats. Sodium and water balances tended to be more positive during ANG II than during phenylephrine infusions. Thus circulating ANG II may stimulate both thirst and salt appetite by a direct action on the brain and not by causing natriuresis or by raising the blood pressure.
Interaction of type I and type II corticosteroid receptor stimulation on carcass energy and carcass water
Authors: White B. D. , Edwards G. L. , Martin R. J.
Published: December 2017

The effects of chronic type I and type II corticosteroid receptor stimulation were examined in adrenalectomized Sprague-Dawley rats to quantify the relative contribution of body energy and body water changes to changes in body weight. Adrenalectomy caused a decrease in both body energy and water. Aldosterone (type I agonist) treatment increased body weight gain and returned energy accretion to the level of sham-operated animals. However, most of the change in body weight (72%) was attributable to a change in body water. The aldosterone-induced increase in body weight gain and carcass water were attenuated by RU-28362 (type II receptor agonist) infusion, suggesting that type II receptor stimulation can antagonize the effect of type I receptor stimulation. Changes in carcass water were paralleled by changes in soluble carcass sodium. Despite alterations in soluble body sodium, no measurable differences in cumulative sodium retention were found. These findings confirm previous studies suggesting an effect of type I receptor stimulation on energy accretion. However, they also caution that changes in body weight cannot be equated with changes in body energy.
Human immunodeficiency virus envelope glycoprotein 120 alters sleep and induces cytokine mRNA expression in rats [published errata appear in Am J Physiol 1996 Aug;271(2 Pt 2):section R following table of contents and 1996 Dec;271(6 Pt 3):section R following table of contents]
Authors: Opp M. R. , Rady P. L. , Hughes T. K. , Cadet P. , Tyring S. K. , Smith E. M.
Published: December 2017

Sleep is altered during the course of viral infection, including that in which the human immunodeficiency virus (HIV) is the etiologic agent. Alterations in the sleep of HIV-infected individuals occur early in the course of infection, prior to the onset of AIDS. The mechanisms for such alterations in sleep are not known. The HIV envelope glycoprotein 120 (gp120) induces the synthesis and secretion of cytokines that enhance [e.g., interleukin (IL)-1 and tumor necrosis factor] and suppress (e.g., IL-10 and IL-1 receptor antagonist) sleep. We used a well-defined rat model to test the hypothesis that the HIV gp120 alters sleep. Recombinant HIV-1IIIB gp120 was injected intracerebroventricularly (20- 500 ng) into rats prior to dark onset. Sleep-wake behavior was not altered after the 20-ng dose, whereas both non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) were initially enhanced and subsequently suppressed after the 100-ng dose. NREMS was enhanced for 8 h after the 500-ng dose; REMS was not affected by this dose. Brain temperature was not altered by any of the gp120 doses used in this study. In addition, mRNA expression for IL-1 beta and IL-10 was induced in the hypothalamus by gp120; this brain region is crucial for the regulation of sleep. These new data support the hypothesis that altered cytokine concentrations within the central nervous system play a pivotal role in the complex alterations in sleep observed during HIV infection.
Cold-induced expression of the metallothionein-1 gene in brown adipose tissue of rats
Authors: Beattie J. H. , Black D. J. , Wood A. M. , Trayhurn P.
Published: December 2017

Heat production by brown adipose tissue (BAT) is important for thermoregulation in a cold environment. During thermogenesis, oxygen utilization increases, with an associated rise in free radical generation. Our objective was to investigate the expression of metallothionein (MT), which is thought to have an antioxidant role in BAT of rates transferred from 25 to 6 degrees C for 6 or 24 h or maintained at 25 degrees C throughout the study (control group). For comparison, MT expression was also measured in white adipose tissue (WAT), liver, and kidney. MT-1 mRNA and 18S rRNA were measured by Northern blotting using specific digoxigenin-labeled antisense oligonucleotide probes with chemiluminescence detection, and MT-1 protein was determined by radioimmunoassay. MT-1 mRNA in BAT increased after 6 h, and the mRNA level after 24 h was equivalent to that in liver 6 h after injection of rats with 10 mg Zn/kg. By 24 h, liver and kidney MT-1 protein had increased relative to the controls by 3- and 1.4-fold, respectively, but in BAT the relative induction was 16-fold. Zn injection did not affect BAT MT-1. As with MT-1 protein, Zn in BAT increased only after 24-h cold exposure. WAT MT-1 was not affected by any treatment. It is concluded that could exposure induces MT-1 in BAT, but in contrast to other tissues induction may be independent of Zn.
Effect of NaCl load administered to the fetus on the bidirectional movement of 51Cr-EDTA across rat placenta
Authors: Stulc J. , Stulcova B.
Published: December 2017

A hypothesis that, in the rat, fluid circulates across the placenta, with circulation being maintained by active transport of Na+ from mother to fetus, has been tested. Transfer of 51Cr-EDTA from mother to fetus and from fetus to mother has been measured and the respective unidirectional transfer constants, Kmf and Kfm, have been calculated. Immediately before the transfer measurement, the fetuses were injected intravenously with 10 microliters of isotonic glucose (controls); with 30 or 300 microliters of isotonic saline; or with 10, 30, or 60 microliters of 9% NaCl. In controls, Kmf of 51Cr-EDTA was 2.0 +/- 0.6 microliters/min, and Kfm was 4.3 +/- 1.0 microliters/min. Injecting the fetus with NaCl had no effect on Kmf, whereas the Kfm was increased significantly in a dose-dependent way. In other experiments, 51Cr-EDTA was injected into nephrectomized maternal animals, and the radioactivity of maternal and fetal plasma was followed for 30 h. The time course of fetal plasma radioactivity supported the thesis that the transfer of 51Cr-EDTA across the rat placenta is highly asymmetrical.
Increased NaCl preference of rats fed low-protein diet
Authors: Okiyama A. , Torii K. , Tordoff M. G.
Published: December 2017

Four studies were conducted to assess the effect of a low-protein diet on NaCl intake. Young rats fed either control (20% casein) or low-protein (5% casein) high-carbohydrate (CHO) diet were allowed to drink either water alone or water and 300 mM NaCl. Relative to rats fed control diet, rats fed the low-protein diet progressively increased NaCl intake so that, despite lower food and water intakes, they drank 180% more NaCl during the last 3 days of the 21-day test. Additional studies found that rats fed low-protein diet always maintained positive sodium balance, were neither sodium depleted nor hypovolemic, and had normal plasma renin activity and aldosterone concentrations. The elevated NaCl intake was not secondary to calcium deficiency and was unaffected by mineral supplementation of the protein-deficient diet. Increases in the diet's CH and/or fat content incidental to decreases in its protein content influenced, but could not completely account for, the effect of protein deficiency on NaCl intake. We conclude that protein deficiency is the primary cause of the elevated NaCl preference produced by being fed a low-protein diet and that a novel physiological mechanism underlies this behavior.
Effects of gold thioglucose on neuropeptide Y messenger RNA levels in the mouse hypothalamus
Authors: Marks J. L. , Waite K. , Cameron-Smith D. , Blair S. C. , Cooney G. J.
Published: December 2017

Elevated hypothalamic neuropeptide Y (NPY) expression is found in several rodent genetic models of obesity, but any association in nongenetic models of obesity is unclear. Consequently, we have measured NPY mRNA levels in the ventromedial hypothalamus of a well-characterized model of obesity, the gold thioglucose (GTG)-injected mouse. Fourteen days after injection (early stage), animals were hyperphagic but not obese, hyperglycemic, or overtly hyperinsulinemic. Ten weeks after treatment (late stage), animals were obese, markedly hyperinsulinemic, and hyperglycemic. In both the early and late stages, NPY mRNA levels were reduced in the arcuate nucleus of GTG-injected animals. Although overnight fasting doubled NPY mRNA levels in control animals, there was no change at either stage in GTG-injected animals. NPY mRNA levels in the deep layers of the cerebral cortex and in the dentate gyrus were not affected by GTG treatment or overnight fasting. We conclude that GTG treatment reduces the expression of NPY mRNA in the arcuate nucleus and that, therefore, increased hypothalamic NPY expression is unlikely to be an important factor causing the obesity and other metabolic changes found in this model.
Neostigmine in the hippocampus increases thermogenesis and T4-to-T3 conversion
Authors: Monda M. , Papa A. , Brizzi G. , DeLuca B.
Published: December 2017

The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (TIBAT and TC), and O2 consumption were monitored in urethan-anesthetized male Sprague-Dawley rats. These variables were measured for 40 min before (baseline values) and 40 min after a neostigmine (5 x 10(-7) mol) or saline injection in the hippocampus. The blood level of 3,5,3'-triiodothyronine and L-thyroxine (T3 and T4) and the 5'-deiodinating activity of IBAT, liver, and kidneys were determined in other rats with neostigmine or saline injection. The results showed that neostigmine injection increased firing rate, TIBAT, TC, O2 consumption, blood level of T3, and 5'-deiodinating activity of IBAT. No change was found in the T4 level and in 5'-deiodinating activity of the liver and kidneys. These findings suggest that neostigmine injection in the hippocampus increases heat production by stimulating sympathetic nerves to IBAT and by elevating the blood level of T3.
Renal responses to amino acids in the sheep fetus
Authors: Woods L. L. , Hohimer A. R. , Davis L. E.
Published: December 2017

Adult animals and humans are known to increase renal blood flow and glomerular filtration rate (GFR) in response to an acute protein load or amino acid infusion; however, the ontogeny of this phenomenon is not known. This study was designed to test the hypothesis that, despite normally high baseline amino acid levels in the fetus, increases in plasma amino acids stimulate increases in GFR before birth. Eight chronically instrumented fetal sheep (126 +/- 1 days gestation) were infused with a mixture of amino acids (0.15 and 0.30 mmol . kg-1 . min-1 i.v.). Plasma alpha-amino nitrogen levels increased significantly from 7.1 +/- 0.3 to 13.0 +/- 0.9 and 25.5 +/- 2.1 mg/dl, respectively, in response to the two doses, and GFR increased significantly from 3.2 +/- 0.4 to 4.0 +/- 0.5 and 4.6 +/- 0.5 ml/min, respectively. Arterial pressure did not change. Renal amino acid reabsorption was significantly increased at all time points during the amino acid infusion, reaching a value nearly five times that of control by the last clearance period. Na+ reabsorption was also increased throughout the infusion. Na+, K+, and Cl- excretions increased significantly only at the very last time point. These data indicate that the mechanism or mechanisms responsible for amino acid-induced hyperfiltration are present and functional even before birth in the sheep. Because maternal eating patterns and protein intake are known to change maternal plasma amino acid levels and amino acids are actively transported across the placenta, our findings suggest that both acute and chronic changes in maternal protein intake may alter fetal renal function.
A comparison of the effects of food deprivation and 2,5-anhydro-D-mannitol on metabolism and ingestion
Authors: Park C. R. , Benthem L. , Seeley R. J. , Friedman M. I. , Wilkinson C. W. , Woods S. C.
Published: December 2017

Using respiratory quotient as an index of metabolic state, we compared the effects of administrations of the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) at a dose of 300 mg/kg with the effect of 10 h of food deprivation. We measured behavioral and physiological responses of the animals receiving the two treatments, including food intake, energy expenditure, rates of carbohydrate and fatty acid utilization, and plasma levels of glucose, insulin, corticosterone, epinephrine, and norepinephrine. A vehicle-treated control group was also included. Fasting produced a greater food intake than 2,5-AM administration. Although plasma glucose, insulin, and norepinephrine levels were similar between the two treatments, plasma corticosterone and epinephrine levels were significantly elevated in animals receiving 2,5-AM. We conclude that although 2,5-AM can produce a metabolic state similar to fasting, as measured by an index of whole body metabolic state (respiratory quotient), there remain factors that influence food intake that are not similar in the two conditions.
Interrelationships between muscle morphology, insulin action, and adiposity
Authors: Kriketos A. D. , Pan D. A. , Lillioja S. , Cooney G. J. , Baur L. A. , Milner M. R. , Sutton J. R. , Jenkins A. B. , Bogardus C. , Storlien L. H.
Published: December 2017

There is evidence that insulin resistance and obesity are associated with relative increases in the proportion of glycolytic type IIb muscle fibers and decreases in the proportion of oxidative type I fibers. Futhermore, insulin resistance and obesity are associated with the fatty acid (FA) profile of structural membrane lipids. The present study was undertaken to define interrelationships between muscle fiber type and oxidative capacity, muscle membrane FA composition, and insulin action and obesity. Muscle morphology, insulin action, and body fat content were measured in 48 male nondiabetic Pima Indians. Percent body fat (pFAT, determined by hydrodensitometry) correlated negatively with percentage of type I fibers (r = -0.44, P = 0.002) and positively with percentage of type IIb fibers (r = 0.40, P = 0.005). Consistent with this finding, pFAT was also significantly related to oxidative capacity of muscle, as assessed by NADH staining (r = -0.47, P = 0.0007) and citrate synthase (CS) activity (r = -0.43, P = 0.008). Insulin action was correlated with oxidative capacity (CS; r = 0.41, P = 0.01) and weakly correlated with percentage of type IIb fibers (r = -0.29, P = 0.05). In addition, relationships were shown between muscle fiber type and FA composition (e.g., percentage of type I fibers related to n-3 FA; r = 0.37, P = 0.01). Thus leaness and insulin sensitivity are associated with increased oxidative capacity and unsaturation of membranes in skeletal muscle. Present studies support the hypothesis that muscle oxidative capacity and fiber type may play a genetically determined or an environmentally modified role in development of obesity and insulin resistance.
Anorexia induced by cytokine interactions at pathophysiological concentrations
Authors: Sonti G. , Ilyin S. E. , Plata-Salaman C. R.
Published: December 2017

Interleukin (IL)-1 beta, IL-8, and tumor necrosis factor-alpha (TNF-alpha) induce anorexia when administered intracerebroventricularly at doses that yield estimated pathophysiological concentrations reported in the cerebrospinal fluid (CSF). Our hypothesis is that pivotal cytokines released during pathological processes interact to induce anorexia during disease. In the present study, we investigated the effects of the intracerebroventricular microinfusion of individual or multiple combinations (8 dyads and 5 triads) of IL-1 beta, IL-8, and TNF-alpha on feeding and the microstructure of eating in rats maintained ad libitum. Estimated pathophysiological concentrations of cytokine combinations exhibited additive or synergistic activities in inducing anorexia. Computerized analysis of behavioral patterns demonstrated that the most effective treatment (triad of 1.0 ng IL-1 beta + 20 ng IL-8 + 20 ng TNF-alpha/rat, n = 11) decreased nighttime meal size by 42% and feeding rate (meal size/meal duration) by 26%, whereas it increased the satiety ratio (postprandial intermeal intervals/meal size) by 80%; meal duration and meal frequency were not significantly affected. Analysis of meal parameters in 4-h intervals revealed a maximum effect during the first 4-h interval after the intracerebroventricular administration. The time course during this initial 4-h interval analyzed in 10-min periods was similar for IL-8 (n = 10) and TNF-alpha (n = 11), and both were significantly different from the time course induced by IL-1 beta (n = 10) and the most effective triad (n = 11). Intracerebroventricular microinfusion of heat-inactivated triad or intraperitoneal administration of the most effective triad, in doses-equivalent to those administered centrally, had no effect on feeding. The results suggest that estimated pathophysiological concentrations of cytokines in the CSF act centrally and additively or synergistically to decrease feeding, and this effect may participate in the anorexia frequently accompanying pathological processes.
Human immunodeficiency virus envelope glycoprotein 120 alters sleep and induces cytokine mRNA expression in rats
Authors: Opp M. R. , Rady P. L. , Hughes T. K. , Cadet P. , Tyring S. K. , Smith E. M.
Published: December 2017

Pages R963–R970: M. R. Opp, P L. Rady, T. K. Hughes, Jr., P. Cadet, S. K. Tyring, and E. M. Smith. “Human immunodeficiency virus envelope glycoprotein 120 alters sleep and induces cytokine mRNA expression in rats.” On p. R968, Fig. 3 should appear as below.

(See PDF)
Differences in calcium kinetics between adolescent girls and young women
Authors: Wastney M. E. , Ng J. , Smith D. , Martin B. R. , Peacock M. , Weaver C. M.
Published: December 2017

Rapid bone accretion occurs throughout childhood but peaks during adolescence. The achievement of optimal peak bone mass, which can protect against osteoporosis later in life, is greatly dependent on rates of bone accretion. To identify differences in calcium metabolism during rapid vs. slower bone accretion, calcium kinetics were compared in 14 healthy girls aged 11-14 yr and 11 women aged 19-31 yr. Calcium kinetics were measured while subjects were undergoing a calcium balance study in a camp simulating a free-living environment. After 7 days on a diet containing 1,330 mg Ca/day, two stable isotopes were administered (44Ca orally and 42Ca intravenously), and blood samples and all urine and feces were collected for 14 days. Samples were analyzed for total calcium by atomic absorption spectrophotometry and for enrichment of 42Ca and 44Ca by fast atom bombardment mass spectrometry. Data from serum, urine, and feces were analyzed using the Simulation, Analysis and Modeling (SAAM) software. Data were fitted by a three-compartment model; the first pool was the same size in girls and women (1.6 g) but the second and third pools were larger in girls (2.85 vs. 1.66 g and 12 vs. 5 g). Compared with the women, girls absorbed more calcium from the diet (38 vs. 22% or 494 vs. 283 mg/day), excreted less calcium in urine (100 vs. 203 mg/day), deposited more calcium in bone (1,459 vs. 501 mg/day), and resorbed more calcium from the skeleton (1,177 vs. 542 mg/day), whereas endogenous calcium excretion did not differ between girls and women (112 vs. 121 mg/day). Girls retained more calcium than women (282 vs. -41 mg/day) through increased absorption, lower urine excretion, and higher bone turnover.
Naltrexone induces arcuate nucleus neuropeptide Y gene expression in the rat
Authors: Kotz C. M. , Grace M. K. , Briggs J. E. , Billington C. J. , Levine A. S.
Published: December 2017

Neuropeptide Y (NPY) has potent effects on several components of energy metabolism, including increased feeding and decreased brown fat thermogenesis. Negative energy balance, such as food deprivation, increases NPY mRNA in hypothalamic arcuate nucleus (ARC). Naltrexone (NLTX), an opioid receptor antagonist, decreases NPY-induced feeding. We hypothesized that NLTX would alter ARC NPY mRNA and change NPY effects on brown fat. Osmotic minipumps prefilled with either saline or NLTX (70 micrograms/h) were implanted subcutaneously in 32 male Sprague-Dawley rats. One-half of the rats were food deprived and one-half were allowed food ad libitum for 48 h. Food intake was measured at 24 and 48 h. At 48 h, ARC NPY mRNA and brown fat uncoupling protein (UCP) mRNA levels were determined using cDNA probes. Forty-eight-hour food intake was significantly decreased by 24% after NLTX infusion. Food deprivation and NLTX treatment significantly and independently increased ARC NPY mRNA and decreased UCP mRNA levels in brown fat, suggesting a complex interaction between hypothalamic NPY and endogenous opioids in the regulation of energy balance.
Subcellular mechanisms of angiotensin II and arginine vasopressin activation of area postrema neurons
Authors: Consolim-Colombo F. M. , Hay M. , Smith T. C. , Elizondo-Fournier M. , Bishop V. S.
Published: December 2017

Angiotensin II (ANG II) and arginine vasopressin (AVP) act on area postrema (AP) neurons to modulate the baroreflex. Because activation of AP neurons by either ANG II or AVP increases intracellular free Ca2+ concentrations ([Ca2+]i), the goal of this study was to analyze the factors affecting the [Ca2+]i responses to ANG II and AVP. Neurons were recovered from 14- to 16-day old rats and studied after 8-14 days in culture by use of the microscopic digital image analysis for fura 2-loaded cells. The effects of ANG II (100 nM) and AVP (100 nM) on [Ca2+]i were determined in normal (2 mM) and low (< 10 nM) extracellular Ca2+ concentrations. In 143 of 240 neurons, ANG II increased [Ca2+]i 4.65-fold after 20 s, and a similar response was observed in the absence of extracellular Ca2+ (3.65-fold after 20 s). After 60 s of observation, steady-state levels of increased [Ca2+]i were still present under both conditions. Pretreatment with AT1 antagonist or pertussis toxin abolished the response to ANG II. AVP also increased [Ca2+]i (3.6-fold at peak, 20 s) in normal and low extracellular Ca2+. Pretreatment with AVP V1 antagonist or pertussis toxin abolished the response to AVP. This study indicates that ANG II-induced increases in [Ca2+]i are independent of extracellular Ca2+ concentrations and involve the activation of AT1 receptors and a pertussis toxin-sensitive G protein. Although AVP affects a fewer number of AP neurons, the mechanisms of activation are also independent of extracellular Ca2+ concentration and are mediated by a pertussis toxin-sensitive G protein.
Effects of photoperiod and androgen on pituitary function and neuropeptide staining in Siberian hamsters
Authors: Bittman E. L. , Jetton A. E. , Villalba C. , Devries G. J.
Published: December 2017

Short photoperiods decrease gonadotropin secretion in Siberian hamsters, but it is unknown whether the negative feedback effects of androgens are amplified under such conditions, as is the case in other species. Photoperiod regulates the synthesis and secretion of gonadotropin-releasing hormone (GnRH), beta-endorphin, and arginine vasopressin (AVP), which influence gonadotropin release and sexual behavior but are themselves regulated by gonadal steroid hormones. To determine the role of androgen in these effects of daylength, immunostaining and gonadotropin concentrations were examined after 8 wk of exposure to long or short days (LD or SD). Animals were either left intact, castrated, or castrated with immediate or delayed replacement of testosterone (T). We also investigated effects of age on photoperiodic influences on brain peptides and serum hormone levels. Serum prolactin concentrations were regulated by photoperiod and by gonadal status in LD hamsters. Effects of T on follicle-stimulating hormone secretion were more pronounced in SD hamsters. Older hamsters were generally less responsive to effects of daylength on pituitary function. Photoperiod and gonadal status regulated the number of AVP-immunoreactive (ir) cells in the bed nucleus of the stria terminalis and the medial amygdala. Androgen treatment yielded more AVP-ir neurons in LD than in SD. Photoperiod influenced the number of GnRH-ir cells only in the medial septum of castrated hamsters. Daylength regulated beta-endorphin-ir neurons in intact hamsters, but not in castrates. Only among old hamsters did photoperiod affect the influence of T on beta-endorphin staining in neurons and fibers. Such fiber staining was unaffected by photoperiod in intact and T-treated castrate hamsters, but was reduced in SD castrates. We conclude that daylength modulates the effects of androgen on gonadotropin secretion and influences the effect of T on neuropeptide staining in regionally specific patterns that depend on the age of the animal and its history of prior steroid exposure.
Leptin-induced decrease in food intake is not associated with changes in gastric emptying in lean mice
Authors: Barrachina M. D. , Martinez V. , Wei J. Y. , Tache Y.
Published: December 2017

Chronic treatment with leptin regulates body weight and energy balance and reduces food intake in obese and lean mice. In 18- to 20-h fasted lean mice (C57BL/6, +/+), we examined the acute effect of a single intraperitoneal injection of recombinant mouse leptin (0.12 mg/kg) on food intake and gastric emptying. Leptin reduced food intake, with a peak inhibition at the 5th h postinjection (69 +/- 12%/h), although there was no change in food consumption at the 1st h. Leptin did not alter the 4-h rate of gastric emptying of a solid nutrient meal (free access to Purina chow for either 1-, 2-, or 4-h period). In normal Sprague-Dawley rats fasted for 18-20 h, a single intraperitoneal injection of recombinant mouse leptin (0.2 or 1.2 mg/kg) did not modify the 7-h cumulative or hourly food intake. These results show that a single intraperitoneal injection of recombinant mouse leptin reduces food intake within 5 h while not influencing gastric emptying of ingested food in lean mice. Sprague-Dawley rats are unresponsive to the food intake-reducing effect of a single intraperitoneal injection of mouse leptin at a dose 10-fold higher than that shown to be effective in mice within the first 4-7 h postinjection.
Gigantocellular vasodepressor area is tonically active and distinct from caudal ventrolateral vasodepressor area
Authors: Aicher S. A. , Reis D. J.
Published: December 2017

The gigantocellular depressor area (GiDA) is a functionally defined subdivision of the medullary gigantocellular reticular formation where vasodepressor responses are evoked by glutamate microinjections (Aicher, S. A., D. J. Reis, D. A. Ruggiero, and T. A. Milner. Neuroscience 60: 761-779, 1994). The present experiments sought to determine whether the GiDA 1) tonically inhibits the sympathetic nervous system; 2) is necessary for baroreflex function; and 3) is functionally distinct from adjacent vasodepressor regions in the medullary reticular formation, including the midline raphe nuclei and the caudal ventrolateral medulla (CVL). Excitotoxic lesions of the GiDA abolished the baroreflex and significantly increased sympathetic nerve activity in anesthetized rats. Equivalent injections into the midline raphe nuclei elevated sympathetic activity but did not alter baroreflex responses. Therefore, the GiDA is functionally distinct from the raphe nuclei, although both contain tonically active sympathoinhibitory neurons. Because the effects of GiDA lesions were identical to those seen after lesions of the CVL, further studies were required to demonstrate that the GiDA and CVL are functionally and anatomically distinct. First, intramedullary injections of kynurenic acid produced hypertension and blocked the baroreflex when placed in the CVL, but not when placed in the GiDA. Second, muscimol inactivation of the RVL blocked the hypertension produced by excitotoxic lesions of the CVL, but failed to block the hypertension produced by similar lesions of the GiDA. Third, CVL neurons project to the RVL but not the spinal cord, whereas GiDA neurons project to the spinal cord but not the RVL. These studies show that the CVL and GiDA are both tonically sympathoinhibitory regions, but they are distinct with regard to their functional connectivity with other autonomic regions.
Intragastric hypertonic saline increases vasopressin and central Fos immunoreactivity in conscious rats
Authors: Carlson S. H. , Beitz A. , Osborn J. W.
Published: December 2017

Although experimental evidence supports peripheral osmoreceptor modulation of arginine vasopressin (AVP) release, a local osmotic signal required for osmoreceptor activation has yet to be identified using physiological sodium loads. Additionally, the central pathway involved in peripheral control of AVP has not been clearly established. Experiments were conducted to examine the effect of intragastric saline on portal venous osmolarity, plasma AVP (P(AVP)), and Fos immunoreactivity. In anesthetized rats, intragastric infusion (2.9 ml) of hypertonic (600 mosM) saline significantly increased portal venous osmolarity while systemic blood osmolarity remained constant. In conscious rats, intragastric hypertonic saline significantly elevated P(AVP) (3.6 +/- 1.3 to 5.8 +/- 1.9 pg/ml), whereas no changes were observed in plasma osmolarity in either the isotonic (296.2 +/- 1.4 to 297.6 +/- 1.1 mosM) or hypertonic (291.7 +/- 1.7 to 291.4 +/- 1.8 mosM) group. Finally, intragastric hypertonic saline significantly increased Fos immunoreactivity in the nucleus of the solitary tract (NTS), area postrema (AP), lateral parabrachial nucleus (LPBN), supraoptic nucleus (SON), and paraventricular nucleus (PVN). These results indicate that intragastric hypertonic saline produces a portal venous osmotic signal that triggers peripheral osmoreceptors to stimulate AVP release while activating the NTS, AP, and LPBN in addition to the SON and PVN.