bluuebunny/crossref_metadata_2025 huggingface dataset:
Selectivity of fatty acid mobilization: a general metabolic feature of adipose tissue
Authors: Raclot T. , Mioskowski E. , Bach A. C. , Groscolas R.
Published: December 2017

This study extends our earlier work (T. Raclot and R. Groscolas. J. Lipid Res. 34: 1515-1526, 1993), which showed that, under norepinephrine-stimulated lipolysis, fatty acids of rat retroperitoneal fat cells are selectively mobilized. The present study examines whether this selective mobilization of fatty acids 1) is based on their proportions in adipose tissue, 2) is a metabolic feature common to all adipose tissues, and/or 3) depends on the lipolysis-stimulating agent. Rat fat cells with two markedly different fatty acid compositions were isolated from four white adipose tissues and treated with three lipolytic agents. Fatty acid composition of in vitro released free fatty acids was compared with that of fat cell triacylglycerols, the ratio of percent in free fatty acid to percent in triacylglycerol being defined as the relative mobilization rate (RMR). The RMR of individual fatty acids was related to their molecular structure. It increased exponentially with unsaturation for a given chain length and decreased with increasing chain length for a given unsaturation. The selectivity of fatty acid mobilization was similar regardless of the fatty acid composition of adipose tissue, the tissue location, and the lipolytic agent used. Under conditions of stimulated lipolysis, the selectivity of fatty acid mobilization is therefore a general metabolic feature of adipose tissue. Fatty acids with 16-20 carbon atoms and 4 or 5 double bonds had the highest RMR (from 1.4 to > 5), whereas fatty acids with 20-22 carbon atoms and 0 or 1 double bond had the lowest RMR (from 0.3 to 0.7). For the other fatty acids, RMR was close to unity.(ABSTRACT TRUNCATED AT 250 WORDS)
Structure and concentrating ability of the mammalian kidney: correlations with habitat
Authors: Beuchat C. A.
Published: December 2017

Mammals with relatively long loops of Henle for their body size tend to have greater than average urinary concentrating ability, but the relationship between urine osmolality (Uosm) and absolute length of the loop of Henle (generally estimated as medullary thickness) is neither proportional nor direct. Uosm is independent of the thickness of the outer medulla (corresponding to the length of the medullary thick ascending limb), which scales similarly with body mass in animals from mesic, arid, and freshwater environments. After adjustment for the effect of body size, there is a significant relationship between the thickness of the inner medulla (corresponding to length of the thin ascending limb) and concentrating ability, but only in species from mesic environments; for these, the thickness of the inner medulla accounts for only 16% of the interspecific variability in Uosm. In marine mammals, both the cortex and medulla are surprisingly thin, yet these animals produce very concentrated urine for their size. A functional dependence of urinary concentrating ability on the length of the loop of Henle is a central tenet of countercurrent multiplier theory, but the correlation of maximum urine concentration with loop length is weak at best and largely reflects the influence of the thin ascending limb.
Effects of meal size on postprandial responses in juvenile Burmese pythons (Python molurus)
Authors: Secor S. M. , Diamond J.
Published: December 2017

Pythons were reported previously to exhibit large changes in intestinal mass and transporter activities on consuming meals equal to 25% of the snake's body mass. This paper examines how those and other adaptive responses to feeding vary with meal size (5, 25, or 65% of body mass). Larger meals took longer to pass through the stomach and small intestine. After ingestion of a meal, O2 consumption rates rose to up to 32 times fasting levels and remained significantly elevated for up to 13 days. This specific dynamic action equaled 29-36% of ingested energy. After 25 and 65% size meals, plasma Cl- significantly dropped, whereas plasma CO2, glucose, creatinine, and urea nitrogen increased as much as a factor of 2.3-4.2. Within 1 day the intestinal mucosal mass more than doubled, and masses of the intestinal serosa, liver, stomach, pancreas, and kidneys also increased. Intestinal uptake rates of amino acids and of D-glucose increased by up to 43 times fasting levels, whereas uptake capacities increased by up to 59 times fasting levels. Magnitudes of many of these responses (O2 consumption rate, kidney hypertrophy, and D-glucose and L-lysine uptake) increased with meal size up to the largest meals studied; other responses (Na+-independent L-leucine uptake, plasma Cl-, and organ masses) plateaued at meals equal to 25% of the snake's body mass; and still other responses (nutrient uptake at day 1, passive glucose uptake, and plasma protein and alkaline phosphatase) were all-or-nothing, being independent of meal size between 5 and 65% of body mass. Pythons undergo a wide array of postprandial responses, many of which differ in their sensitivity to meal size.
Hard training for 5 mo increases Na(+)-K+ pump concentration in skeletal muscle of cross-country skiers
Authors: Evertsen F. , Medbo J. I. , Jebens E. , Nicolaysen K.
Published: December 2017

To study how training affects the Na(+)-K+ pump concentration, 11 male and 9 female elite junior cross-country skiers trained 12-15 h/wk at 60-70% (moderate-intensity group) or 80-90% (high-intensity group) of their maximal O2 uptake for 5 mo. Muscle biopsies taken from the vastus lateralis muscle before and after the training period were analyzed for Na(+)-K+ pump concentration by the [3H]ouabain-binding technique. Before training, the concentration was 343 +/- 11 nmol/kg wet muscle mass (mean +/- SE) for the men and 281 +/- 14 nmol/kg for the women (18% less than for the men, P = 0.003). The Na(+)-K+ pump concentration rose by 49 +/- 11 nmol/kg (16%, P < 0.001) for all subjects pooled during the training period, and there was no difference between the two training groups (P = 0.3) or the sexes (P = 0.5) in this increase. The Na(+)-K+ pump concentration correlated with the maximal O2 uptake (r = 0.6, P = 0.003), with the performance during a 20-min treadmill run (r = 0.6, P = 0.003), and to the rank of the subjects' performance as cross-country skiers (Spearman's rank correlation coefficient = 0.76, P < 0.001). These data could mean that for elite cross-country skiers the performance is related to the Na(+)-K+ pump concentration. However, other studies have shown an equally high pump concentration for far less fit subjects, suggesting that the pump concentration may not be a limiting factor.
Local constriction of arteriovenous anastomoses in the cooled finger
Authors: Bergersen T. K. , Eriksen M. , Walloe L.
Published: December 2017

We have examined the influence of local cooling from 35 to 19 degrees C on spontaneous arterial blood velocity fluctuations in the acral skin of thermoneutral subjects. The skin temperature of one hand was gradually lowered in a water bath in two separate experimental runs. Simultaneous continuous blood velocity was measured from the third finger artery of both hands using ultrasound-Doppler. The large blood velocity fluctuations assumed to be caused by synchronous vasomotion of the arteriovenous anastomoses were invariably seen in the control finger artery throughout the two cooling periods, indicating that the subjects were in their thermoneutral zone. The velocity fluctuations on the cooled side remained nearly unchanged and closely correlated with those in the control finger artery during local cooling from 35 to approximately 21.5 degrees C. Below this temperature (range 23-20 degrees C) the velocity fluctuations ceased abruptly, and the velocity was nonfluctuating and continuously low. These results indicate a local thermal level below which there is abrupt, sustained closure of the arteriovenous anastomoses.
Reduced proximal reabsorption resets tubuloglomerular feedback in euvolemic rats
Authors: Thomson Scott C. , Vallon Volker , Blantz Roland C.
Published: December 2017

Inhibition of renal carbonic anhydrase reduces proximal reabsorption and activates tubuloglomerular feedback (TGF). The TGF response is saturable, with highest gain focused near the natural flow rate. Therefore, any large change imposed on ambient tubular flow should reduce the TGF response to subequent flow perturbations. However, TGF tends to align with ambient flow regardless of the rate of ambient flow, suggesting that TGF resets to accommodate changes in flow while maintaining feedback efficiency. We used micropuncture and videometric flow velocitometry to test for TGF resetting in free-flowing nephrons during systemic infusion of the carbonic anhydrase inhibitor benzolamide (BNZ, 5 mg ⋅ kg−1⋅ h−1) in euvolemic rats. Late proximal flow (VLP) and the fractional compensation (C) of TGF for perturbations in VLPwere assessed repeatedly before and during BNZ. Early on, BNZ reduced C, consistent with TGF saturation. Over the next 45–60 min, VLPincreased gradually by ∼5 nl/min as C recovered to pre-BNZ levels. BNZ also increased VLPby ∼5 nl/min when TGF was rendered inoperative by intratubular wax block, but this increase occurred rapidly. These data demonstrate rightward resetting of TGF during reduced proximal reabsorption.
Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo
Authors: Cheeseman C. I.
Published: December 2017

The effect of in vivo infusion of the peptide hormone glucagon-like peptide 2 (GLP-2) on glucose transport across the rat jejunal brush-border membrane (BBM) was assessed using isolated membrane vesicles. A 2-h infusion of GLP-2 produced a marked acceleration of sodium-dependent glucose uptake into BBM vesicles with a significant overshoot. There was no change in vesicle space or permeability resulting from the hormone infusion. Kinetic analysis showed this stimulation to be the result of a threefold increase in the maximal rate of transport, with no consistent change in the affinity constant ( Km). The time course of this response showed that the effect was observable, but smaller, after only 30 min of hormone infusion and was maximal after 1 h. Sodium-dependent phloridzin binding to the membrane vesicles showed a parallel increase in maximal binding after 1 and 2 h of hormone infusion. Western blotting showed a similar increase in sodium-dependent glucose transporter 1 (SGLT-1) abundance. The effect of GLP-2 could be blocked by luminal brefeldin A or wortmannin. These results indicate that GLP-2 is able to induce trafficking of SGLT-1 from an intracellular pool into the BBM within 60 min and that phosphoinositol 3-kinase may well be involved in the intracellular signaling pathway in this response.
Fat pad-specific compensatory mass increases after varying degrees of lipectomy in Siberian hamsters
Authors: Mauer Mary Margaret , Bartness Timothy J.
Published: December 2017

Long day-housed Siberian hamsters show compensatory mass increases in inguinal (I) white adipose tissue (WAT) after epididymal WAT pad (EWAT) removal (x) but do not increase EWAT mass after IWATx. This study tested whether EWAT is specifically unresponsive to IWATx or whether EWAT lacks responsiveness to body fat deficits in general. We also tested whether the compensatory mass increases that occur after side-specific body fat removal are unilateral or bilateral. Therefore EWAT and/or IWAT was removed unilaterally or bilaterally. The compensatory changes in WAT mass by the intact fat pads were measured 12 wk later. EWAT did not compensate for removal of its contralateral mate. Retroperitoneal WAT and IWAT showed greater compensatory mass increases ipsilateral to the side of fat pad removal when EWAT or IWAT pads were removed unilaterally but not after removal of larger amounts of body fat. These results suggest the following: 1) in general, the greater the lipectomy-induced lipid deficit, the greater is the relative fat pad mass compensation; 2) the restoration of body fat content after lipectomy may involve mechanisms that can detect the side of the lipid deficit and enhance fat deposition on this side; and 3) EWAT does not show compensatory mass increases after lipectomy.
PVN infusion of GLP-1-(7—36) amide suppresses feeding but does not induce aversion or alter locomotion in rats
Authors: McMahon Lance R. , Wellman Paul J.
Published: December 2017

Intracerebroventricular infusion of glucagon-like peptide-1-(7—36) amide (GLP-1) reduces feeding in rats, an effect that could be localized to the hypothalamic paraventricular nucleus (PVN). Intracerebroventricular GLP-1, however, may also induce conditioned taste aversion (CTA), thereby putting into question the specificity of the action of GLP-1 on feeding. The present experiments evaluated the action of PVN GLP-1 (0, 100, or 200 ng) on induction of CTA, on locomotion, and finally, on feeding and drinking in rats. PVN infusion of GLP-1 (100 or 200 ng) did not support the induction of CTA and did not reliably alter locomotion, but did suppress feeding and drinking. The present study suggests that GLP-1 infusions into the PVN reduce food and water intake without producing illness or disrupting locomotor behavior. These data, in conjunction with reports of increased feeding following antagonism of central GLP-1 receptors, support the notion that endogenous GLP-1, perhaps within the PVN, functions to suppress feeding in the rat.
Characterization of the ryanodine receptor/channel of invertebrate muscle
Authors: Quinn Kerry E. , Castellani Loriana , Ondrias Karol , Ehrlich Barbara E.
Published: December 2017

Electron-microscopic analysis was used to show that invertebrate muscle has feetlike structures on the sarcoplasmic reticulum (SR) displaying the typical four-subunit appearance of the calcium (Ca2+) release channel/ryanodine receptor (RyR) observed in vertebrate skeletal muscle (K. E. Loesser, L. Castellani, and C. Franzini-Armstrong. J. Muscle Res. Cell Motil. 13: 161–173, 1992). SR vesicles from invertebrate muscle exhibited specific ryanodine binding and single channel currents that were activated by Ca2+, caffeine, and ATP and inhibited by ruthenium red. The single channel conductance of this invertebrate RyR was lower than that of the vertebrate RyR (49 and 102 pS, respectively). Activation of lobster and scallop SR Ca2+release channel, in response to cytoplasmic Ca2+(1 nM–10 mM), reflected a bell-shaped curve, as is found with the mammalian RyR. In contrast to a previous report (J.-H. Seok, L. Xu, N. R. Kramarcy, R. Sealock, and G. Meissner. J. Biol. Chem. 267: 15893–15901, 1992), our results show that regulation of the invertebrate and vertebrate RyRs is quite similar and suggest remarkably similar paths in these diverse organisms.
Effects of interleukin-1β on sleep are mediated by the type I receptor
Authors: Fang Jidong , Wang Ying , Krueger James M.
Published: December 2017

Interleukin-1β (IL-1β) is a well characterized sleep regulatory substance. To study receptor mechanisms for the sleep-promoting effects of IL-1β, sleep patterns were determined in control and IL-1 type I receptor knockout (IL-1RI KO) mice with a B6x129 background after intraperitoneal injections of saline or murine recombinant IL-1β. The IL-1RI KO mice had slightly but significantly less sleep during the dark period compared with the controls. IL-1β dose dependently increased non-rapid eye movement sleep (NREMS) and suppressed rapid eye movement sleep (REMS) in the controls. The IL-1RI KO mice did not respond to IL-1β. In contrast, the IL-1RI KO mice increased NREMS and decreased REMS after administration of tumor necrosis factor-α (TNF-α), another well characterized sleep-promoting substance. These results 1) provide further evidence that IL-1β is involved in sleep regulation, 2) indicate that the effects of IL-1β on sleep are mediated by the type I receptor, and 3) suggest that TNF-α is capable of inducing sleep without the involvement of IL-1.
Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin
Authors: Havel Peter J. , Uriu-Hare Janet Y. , Liu Tina , Stanhope Kimber L. , Stern Judith S. , Keen Carl L. , Ahrén Bo
Published: December 2017

Evidence for regulation of circulating leptin by insulin is conflicting. Diabetes was induced in rats with streptozotocin (STZ; 40 mg ⋅ kg−1⋅ day−1× 2 days) to examine the effect of insulin-deficient diabetes and insulin treatment on circulating leptin. After 12 wk, plasma leptin concentrations in untreated rats were all <0.4 ng/ml versus 4.9 ± 0.9 ng/ml in control animals ( P < 0.005). In rats treated with subcutaneous insulin implants for 12 wk, which reduced hyperglycemia by ∼50%, plasma leptin was 2.1 ± 0.6 ng/ml, whereas leptin concentrations were 6.0 ± 1.6 ng/ml in insulin-implanted rats receiving supplemental injections of insulin for 4 days to normalize plasma glucose ( P< 0.005 vs. STZ untreated). In a second experiment, plasma leptin was monitored at biweekly intervals during 12 wk of diabetes. In rats treated with insulin implants, plasma leptin concentrations were inversely proportional to glycemia ( r= −0.64; P < 0.0001) and unrelated to body weight ( P = 0.40). In a third experiment, plasma leptin concentrations were examined very early after the induction of diabetes. Within 24 h after STZ injection, plasma insulin decreased from 480 ± 30 to 130 ± 10 pM ( P < 0.0001), plasma glucose increased from 7.0 ± 0.2 to 24.8 ± 0.5 mM, and plasma leptin decreased from 3.2 ± 0.2 to 1.2 ± 0.1 ng/ml (Δ = −63 ± 3%, P < 0.0001). In a subset of diabetic rats treated with insulin for 2 days, glucose decreased to 11.7 ± 3.9 mM and leptin increased from 0.5 ± 0.1 to 2.9 ± 0.6 ng/ml ( P< 0.01) without an effect on epididymal fat weight. The change of leptin was correlated with the degree of glucose lowering ( r = 0.75, P < 0.05). Thus insulin-deficient diabetes produces rapid and sustained decreases of leptin that are not solely dependent on weight loss, whereas insulin treatment reverses the hypoleptinemia. We hypothesize that decreased glucose transport into adipose tissue may contribute to decreased leptin production in insulin-deficient diabetes.
Role of IL-6 and TNF in thermoregulation and survival during sepsis in mice
Authors: Leon Lisa R. , White Andrew A. , Kluger Matthew J.
Published: December 2017

Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) have been implicated as key mediators in inflammation, morbidity, and mortality associated with sepsis. We examined the role of IL-6 and TNF-α signaling on hypothermia, fever, cachexia, anorexia, and survival during sepsis induced by cecal ligation and puncture (CLP) in male and female gene knockout mice. Male wild-type mice developed an initial hypothermia and subsequent fever during sepsis. Male IL-6 knockout mice did not develop fever; rather, they maintained a profound hypothermia during sepsis. Male TNF p55/p75 receptor (TNFR) knockout mice had attenuated hypothermia, but developed a virtually identical fever as wild-type mice. Cachexia did not differ between male wild-type and IL-6 or TNFR knockout mice, whereas anorexia was prolonged in IL-6 knockout mice. Due to the rapid lethality of sepsis in female mice, survival was the only variable we were able to statistically compare among female genotypes. Female wild-type mice had significantly decreased survival compared with male wild-type mice. Survival was significantly enhanced in male and female TNFR knockout mice compared with their wild-type controls. Lack of IL-6 did not affect male or female lethality. These data support the hypothesis that IL-6 is a key mediator of fever and food intake, whereas TNF is responsible for the initial hypothermia and lethality of sepsis in both sexes of mice. The enhanced lethality of CLP-treated female mice supports a role for sex steroids during sepsis.
Uncoupling of the autonomic and cardiovascular systems in acute brain injury
Authors: Goldstein Brahm , Toweill Daniel , Lai Susanna , Sonnenthal Karen , Kimberly Brent
Published: December 2017

We hypothesized that acute brain injury results in decreased heart rate (HR) variability and baroreflex sensitivity indicative of uncoupling of the autonomic and cardiovascular systems and that the degree of uncoupling should be proportional to the degree of neurological injury. We used HR and blood pressure (BP) power spectral analysis to measure neuroautonomic regulation of HR and BP and the transfer function magnitude (TF) between BP and HR as a measure of baroreflex modulation of HR. In 24 brain-injured patients [anoxic/ischemic injury ( n = 7), multiple trauma ( n = 6), head trauma ( n = 5), central nervous system infection ( n = 4), and intracranial hemorrhage ( n = 2)], neurological injury and survival was associated with low-frequency (0.01–0.15 Hz) HR and BP power and TF. Brain-dead patients showed decreased low-frequency HR power [0.51 ± 0.36 (SE) vs. 2.54 ± 0.14 beats/min2, P = 0.03] and TF [0.61 ± 0.16 (SE) vs. 1.29 ± 0.07 beats ⋅ min−1⋅ mmHg−1, P = 0.05] compared with non-brain-dead patients. We conclude that 1) severity of neurological injury and outcome are inversely associated with HR and BP variability and 2) there is direct evidence for cardiovascular and autonomic uncoupling in acute brain injury with complete uncoupling during brain death.
Later endogenous circadian temperature nadir relative to an earlier wake time in older people
Authors: Duffy Jeanne F. , Dijk Derk-Jan , Klerman Elizabeth B. , Czeisler Charles A.
Published: December 2017

The contribution of the circadian timing system to the age-related advance of sleep-wake timing was investigated in two experiments. In a constant routine protocol, we found that the average wake time and endogenous circadian phase of 44 older subjects were earlier than that of 101 young men. However, the earlier circadian phase of the older subjects actually occurred later relative to their habitual wake time than it did in young men. These results indicate that an age-related advance of circadian phase cannot fully account for the high prevalence of early morning awakening in healthy older people. In a second study, 13 older subjects and 10 young men were scheduled to a 28-h day, such that they were scheduled to sleep at many circadian phases. Self-reported awakening from scheduled sleep episodes and cognitive throughput during the second half of the wake episode varied markedly as a function of circadian phase in both groups. The rising phase of both rhythms was advanced in the older subjects, suggesting an age-related change in the circadian regulation of sleep-wake propensity. We hypothesize that under entrained conditions, these age-related changes in the relationship between circadian phase and wake time are likely associated with self-selected light exposure at an earlier circadian phase. This earlier exposure to light could account for the earlier clock hour to which the endogenous circadian pacemaker is entrained in older people and thereby further increase their propensity to awaken at an even earlier time.
Endotoxemia in mice stimulates production of complement C3 and serum amyloid A in mucosa of small intestine
Authors: Wang Quan , Meyer Tory A. , Boyce Steven T. , Wang Jing Jing , Sun Xiaoyan , Tiao Greg , Fischer Josef E. , Hasselgren Per-Olof
Published: December 2017

We examined the effect of endotoxemia in mice on protein and mRNA levels for the acute phase proteins complement C3 and serum amyloid A (SAA) in jejunal mucosa. Endotoxemia was induced in mice by the subcutaneous injection of 250 μg lipopolysaccharide per mouse. Control mice were injected with saline. C3 and SAA were measured by ELISA. Messenger RNA levels were determined by Northern blot analysis or competitive PCR. Immunohistochemistry was performed to determine in which cell type(s) C3 and SAA were present. Mucosal C3 and SAA protein and mRNA levels were increased in endotoxemic mice. Immunohistochemistry showed that C3 was present in both enterocytes and cells of the lamina propria, whereas SAA was seen mainly in lamina propria cells. Results suggest that endotoxemia stimulates production of C3 and SAA in small intestinal mucosa. The response may be regulated at the transcriptional level and probably reflects increased synthesis of the acute phase proteins in both enterocytes and cells of the lamina propria.
Hormonal regulation of leptin expression in broiler chickens
Authors: Ashwell Christopher M. , Czerwinski Susan M. , Brocht Donna M. , McMurtry John P.
Published: December 2017

Leptin, the polypeptide hormone encoded by the obese gene, is secreted by adipose tissue and has been shown to induce satiety and increase energy expenditure in mammals. In this study, we confirmed the presence of a leptin homolog in liver and adipose tissues of broiler chickens. Leptin expression was also detected in chicken embryonic liver and yolk sac. The effects of hormone treatment on leptin expression in chickens were also investigated. Leptin expression in the liver is increased by insulin and dexamethasone and decreased by glucagon and estrogen. There was no induction of leptin expression in adipose tissue by any treatment, whereas only estrogen decreased adipose expression. The differential effect on liver and adipose tissue suggests that adipocytes in chickens may be expressing leptin at a maximal rate or that its mechanism of expression regulation differs from liver. The localization of leptin expression and tissue-specific effects of hormone treatments on leptin expression observed in chickens may indicate a relationship between leptin and avian lipid metabolism.
Regulation of arginase isoforms I and II by IL-4 in cultured murine peritoneal macrophages
Authors: Louis Claudine A. , Mody Vino , Henry William L. , Reichner Jonathan S. , Albina Jorge E.
Published: December 2017

Macrophages can express two arginase isoforms with distinct subcellular localization (cytosolic AI and mitochondrial AII). These isoforms are products of different genes and are capable of differential induction. Experiments were performed to identify the specific arginase isoforms induced by interleukin (IL)-4, a Th2 cytokine shown by others to increase arginase activity in macrophages, and serum. Results indicate IL-4, in concert with serum, increases AI, but not AII, mRNA in cultured murine macrophages. Moreover, they show serum to induce both arginase isoforms and to be required for maximal AI induction by IL-4. Together with the enhanced expression of AI, IL-4 induced the expression of the cationic amino acid transporter MCAT-2 and increasedl-arginine transport into the cells. Present results confirm, then, specificity in the ability of macrophage arginase isoforms to be induced by different stimuli. Moreover, they suggest that a decrease in intracellularl-arginine concentration resulting from its consumption by arginase may be repaired by concurrent increases inl-arginine influx into the cell.
Arcuate NPY neurons and energy homeostasis in diet-induced obese and resistant rats
Authors: Levin Barry E.
Published: December 2017

The neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus regulate and are regulated by short-term changes in energy homeostasis. Both outbred and inbred strains of rats that develop diet-induced obesity (DIO) or are diet resistant (DR) when fed a diet relatively high in energy, fat, and sucrose content (HE diet) were used to study arcuate NPY mRNA expression during long-term changes in energy balance. Outbred, chow-fed obesity-prone rats had 59% higher NPY levels than obesity-resistant rats. After 14 wk on HE diet, DIO rats had 17% lower NPY levels than DR rats made comparably obese on a highly palatable diet. When switched to chow, obese DR rats spontaneously reduced their intake and their body weights fell to control levels in association with a 10% decrease in NPY levels. DIO rats lost weight only with energy restriction associated with a 21% increase in their NPY levels. When again fed ad libitum, the weight and NPY levels in the rats returned to those of unrestricted DIO rats. Chow-fed, inbred DIO rats weigh more and are fatter than age-matched inbred DR rats. As with outbred DIO rats fed the HE diet, inbred DIO rats had 20% lower NPY levels than DR rats. Thus preobese, outbred DIO rats have high levels of NPY message that are not susceptible to metabolic regulation. When obesity develops in both inbred and outbred rats, the levels of NPY mRNA fall but become responsive to alterations in energy availability.
Role of renal medullary adenosine in the control of blood flow and sodium excretion
Authors: Zou Ai-Ping , Nithipatikom Kasem , Li Pin-Lan , Cowley Allen W.
Published: December 2017

This study determined the levels of adenosine in the renal medullary interstitium using microdialysis and fluorescence HPLC techniques and examined the role of endogenous adenosine in the control of medullary blood flow and sodium excretion by infusing the specific adenosine receptor antagonists or agonists into the renal medulla of anesthetized Sprague-Dawley rats. Renal cortical and medullary blood flows were measured using laser-Doppler flowmetry. Analysis of microdialyzed samples showed that the adenosine concentration in the renal medullary interstitial dialysate averaged 212 ± 5.2 nM, which was significantly higher than 55.6 ± 5.3 nM in the renal cortex ( n = 9). Renal medullary interstitial infusion of a selective A1antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 300 pmol ⋅ kg−1 ⋅ min−1, n = 8), did not alter renal blood flows, but increased urine flow by 37% and sodium excretion by 42%. In contrast, renal medullary infusion of the selective A2 receptor blocker 3,7-dimethyl-1-propargylxanthine (DMPX; 150 pmol ⋅ kg−1 ⋅ min−1, n = 9) decreased outer medullary blood flow (OMBF) by 28%, inner medullary blood flows (IMBF) by 21%, and sodium excretion by 35%. Renal medullary interstitial infusion of adenosine produced a dose-dependent increase in OMBF, IMBF, urine flow, and sodium excretion at doses from 3 to 300 pmol ⋅ kg−1 ⋅ min−1( n = 7). These effects of adenosine were markedly attenuated by the pretreatment of DMPX, but unaltered by DPCPX. Infusion of a selective A3receptor agonist, N 6-benzyl-5′-( N-ethylcarbonxamido)adenosine (300 pmol ⋅ kg−1 ⋅ min−1, n = 6) into the renal medulla had no effect on medullary blood flows or renal function. Glomerular filtration rate and arterial pressure were not changed by medullary infusion of any drugs. Our results indicate that endogenous medullary adenosine at physiological concentrations serves to dilate medullary vessels via A2 receptors, resulting in a natriuretic response that overrides the tubular A1 receptor-mediated antinatriuretic effects.
Endogenous thermoregulatory rhythms of squirrel monkeys in thermoneutrality and cold
Authors: Robinson Edward L. , Fuller Charles A.
Published: December 2017

Whole body heat production (HP) and heat loss (HL) were examined to determine if the free-running circadian rhythm in body temperature (Tb) results from coordinated changes in HP and HL rhythms in thermoneutrality (27°C) as well as mild cold (17°C). Squirrel monkey metabolism ( n = 6) was monitored by both indirect and direct calorimetry, with telemetered measurement of Tb and activity. Feeding was also measured. Rhythms of HP, HL, and conductance were tightly coupled with the circadian Tb rhythm at both ambient temperatures (TA). At 17°C, increased HP compensated for higher HL at all phases of the Tb rhythm, resulting in only minor changes to Tb. Parallel compensatory changes of HP and HL were seen at all rhythm phases at both TA. Similar time courses of Tb, HP, and HL in their respective rhythms and the relative stability of Tb during both active and rest periods suggest action of the circadian timing system on Tb set point.
Myoglobin desaturation with exercise intensity in human gastrocnemius muscle
Authors: Molé Paul A. , Chung Youngran , Tran Tuan Khanh , Sailasuta Napapon , Hurd Ralph , Jue Thomas
Published: December 2017

The present study evaluated whether intracellular partial pressure of O2([Formula: see text]) modulates the muscle O2uptake (V˙o2) as exercise intensity increased. Indirect calorimetry followedV˙o2, whereas nuclear magnetic resonance (NMR) monitored the high-energy phosphate levels, intracellular pH, and intracellular[Formula: see text] in the gastrocnemius muscle of four untrained subjects at rest, during plantar flexion exercise with a constant load at a repetition rate of 0.75, 0.92, and 1.17 Hz, and during postexercise recovery.V˙o2increased linearly with exercise intensity and peaked at 1.17 Hz (15.1 ± 0.37 watts), when the subjects could maintain the exercise for only 3 min.V˙o2reached a peak value of 13.0 ± 1.59 ml O2⋅ min−1⋅ 100 ml leg volume−1. The31P spectra indicated that phosphocreatine decreased to 32% of its resting value, whereas intracellular pH decreased linearly with power output, reaching 6.86. Muscle ATP concentration, however, remained constant throughout the exercise protocol. The1H NMR deoxymyoglobin signal, reflecting the cellular[Formula: see text], decreased in proportion to increments in power output andV˙o2. At the highest exercise intensity and peakV˙o2, myoglobin was ∼50% desaturated. These findings, taken together, suggest that the O2gradient from hemoglobin to the mitochondria can modulate the O2flux to meet the increasedV˙o2in exercising muscle, but declining cellular [Formula: see text]during enhanced mitochondrial respiration suggests that O2availability is not limitingV˙o2during exercise.
Temperature-dependent expression of cytochrome-coxidase in Antarctic and temperate fish
Authors: Hardewig I. , van Dijk P. L. M. , Moyes C. D. , Pörtner H. O.
Published: December 2017

Seasonal acclimation versus permanent adaptation to low temperatures leads to a differential response in the expression of cytochrome- c oxidase (CCO) in temperate and Antarctic eelpouts. Although eurythermal eelpout from the North Sea ( Zoarces viviparus) displayed a cold-induced rise of CCO activity in white muscle, enzyme activity in the cold stenothermal Antarctic eelpout Pachycara brachycephalum failed to reflect such a compensatory increase. In Antarctic eelpout, CCO activity correlates with transcript levels of mitochondrial encoded subunits of CCO (CCO I and CCO II), whereas cold-acclimated eelpout from the North Sea show lower enzyme activities than expected on the basis of mitochondrial mRNA levels. In these animals, CCO expression at low temperatures may be limited either by nuclear CCO transcripts or by posttranscriptional processes. These may comprise translation of the subunits or assembly of the CCO holoenzyme. mRNA levels of CCO IV, one of the nuclear encoded subunits, increased strongly during cold acclimation, indicating that the expression of CCO is likely not message limited in cold-acclimated Z. viviparus. Our data suggest that seasonal cold acclimation of Z. viviparus results in a modification of the relationship between transcription and translation or posttranslational processes. In permanently cold-adapted P. brachycephalum, on the other hand, CCO expression shows similar characteristics as in the warm-acclimated confamilial species, e.g., low levels of enzyme activity correlated with low levels of mitochondrial message.
Time-dependent hypoxic ventilatory responses in rats: effects of ketanserin and 5-carboxamidotryptamine
Authors: Kinkead Richard , Mitchell Gordon S.
Published: December 2017

We hypothesized that the 5-hydroxytryptamine (5-HT) active drugs ketanserin and 5-carboxamidotryptamine (5-CT) would modulate time-dependent hypoxic phrenic and hypoglossal responses, including 1) short-term hypoxic response, 2) posthypoxia frequency decline (PHFD), and 3) long-term facilitation (LTF) of respiratory motor output. Phrenic and hypoglossal nerve activities were recorded in urethan-anesthetized, paralyzed, vagotomized, and artificially ventilated rats pretreated either with ketanserin (5-HT2A/Cantagonist; 2 mg/kg iv), 5-CT (5-HT1A/Bagonist; 10 μg/kg iv), or saline (sham). Rats were exposed to three 5-min episodes of hypoxia [fractional inspired O2([Formula: see text]) = 0.11], separated by 5 min of hyperoxia ([Formula: see text] = 0.5). During hypoxia, ketanserin augmented phrenic but not hypoglossal burst amplitude; 5-CT had no effect. Both drugs accentuated PHFD. Ketanserin blocked phrenic LTF; hypoglossal LTF was not apparent, even in sham-treated rats. 5-CT reversed LTF, resulting in a long-lasting depression of phrenic burst frequency and amplitude without effect on hypoglossal burst amplitude. The data suggest that 1) 5-HT2A/Creceptor activation modulates the short-term hypoxic phrenic response and PHFD and is necessary for LTF; and 2) 5-CT may affect time-dependent hypoxic ventilatory responses by reducing serotonin release via 5-HT1A/Bautoreceptor activation.
Responses of celiac and cervical vagal afferents to infusions of lipids in the jejunum or ileum of the rat
Authors: Randich Alan , Tyler William J. , Cox James E. , Meller Stephen T. , Kelm Gary R. , Bharaj Satinder S.
Published: December 2017

Multiunit celiac and single-unit cervical recordings of vagal afferents were performed before and during infusions of fatty acids, triglycerides, or saline into either the ileum or jejunum of the rat. In multiunit recordings, lipids increased activity of vagal afferents to a greater extent than saline. The greatest increases in vagal afferent activity resulted from infusions of linoleic acid, conjugated linoleic acid, or oleic acid. The triglycerides, corn oil or Intralipid, were less effective than the fatty acids in affecting vagal afferent activity. Ileal pretreatment with the hydrophobic surfactant Pluronic L-81 significantly attenuated the response of celiac vagal afferents to ileal infusion of linoleic acid. Single-unit recordings of cervical vagal afferents supported the multiunit data in showing lipid-induced increased vagal afferent activity in ∼50% of ileal units sampled and 100% of a limited number of jejunal units sampled. These data demonstrate that free fatty acids can activate ileal and jejunal vagal afferents in the rat, and this effect can be attenuated by pretreatment with a chylomicron inhibitor. These data are consistent with the view that lipid-induced activation of vagal afferents could be a potential substrate for the inhibitory effects of intestinal lipids on gastrointestinal function, food intake, and body weight gain.
Inhibition of cyclooxygenase-2 prevents inflammation-mediated preterm labor in the mouse
Authors: Gross Gil , Imamura Takuji , Vogt Sherri K. , Wozniak David F. , Nelson D. Michael , Sadovsky Yoel , Muglia Louis J.
Published: December 2017

Prostaglandins (PGs) have proven important during parturition, but inhibition of PG production treating preterm labor (PTL) results in significant maternal and fetal side effects. We hypothesize that specific inhibition of either cyclooxygenase (COX)-1 or -2 may result in separation of therapeutic and toxic effects. We demonstrate that COX-2, but not COX-1, is induced during inflammation-mediated PTL caused by lipopolysaccharide (LPS) administration. A two- to threefold increase in uterine and ovarian PG concentrations coincides with this induction of COX-2. The COX-2-selective inhibitor SC-236 proved effective in stopping preterm delivery and the increases in PGs. The COX-1-selective inhibitor SC-560 also attenuated uterine and ovarian PG production after LPS but did not inhibit PTL as efficiently as SC-236. COX-1-deficient mice, which show delay in the onset of term labor, exhibited no delay in onset of PTL after LPS. These findings suggest that the mechanisms for initiation of inflammation-mediated PTL and term labor differ and that selective COX-2 inhibition may provide a means of stopping inflammation-induced PTL in humans.
Is the spring quality of muscle plastic?
Authors: Reich T. E. , Lindstedt S. L. , LaStayo P. C. , Pierotti D. J.
Published: December 2017

During locomotion, major muscle groups are often activated cyclically. This alternate stretch-shorten pattern of activity could enable muscle to function as a spring, storing and recovering elastic recoil potential energy. Because the ability to store and recover elastic recoil energy could profoundly affect the energetics of locomotion, one might expect this to be an adaptable feature of skeletal muscle. This study tests the hypothesis that chronic eccentric (Ecc) training results in a change in the spring properties of skeletal muscle. Nine female Sprague-Dawley rats underwent chronic Ecc training for 8 wk on a motorized treadmill. The spring properties of muscle were characterized by both active and passive lengthening force productions. A single “spring constant” (Δforce/Δlength) from the passive length-tension curves was calculated for each muscle. Results from measurements on long heads of triceps brachii muscle indicate that the trained group produced significantly more passive lengthening force ( P = 0.0001) as well as more active lengthening force ( P = 0.0001) at all lengths of muscle stretch. In addition, the spring constants were significantly different between the Ecc (1.71 N/mm) and the control (1.31 N/mm) groups. A stiffer spring is capable of storing more energy per unit length stretched, which is of functional importance during locomotion.
Effect of 17β-estradiol on the expression of somatostatin genes in rainbow trout (Oncorhynchus mykiss)
Authors: Holloway Alison C. , Melroe Gregory T. , Ehrman Melissa M. , Reddy P. Konda , Leatherland John F. , Sheridan Mark A.
Published: December 2017

In the present study, the effects of 17β-estradiol (E2) treatment on the expression of preprosomatostatin (PPSS) I, PPSS II′, and PPSS II" mRNA in the hypothalamus and endocrine pancreas (Brockmann body), as well as the effects of E2 treatment on plasma somatostatin (SS)-14 and -25 concentrations in sexually immature rainbow trout ( Oncorhynchus mykiss), were investigated. E2treatment significantly ( P < 0.001) depressed both plasma SS-14 and SS-25. In the hypothalamus, E2 treatment significantly ( P < 0.001) decreased the levels of PPSS I and PPSS II" mRNA. However, there was no effect of E2treatment on PPSS II′ mRNA levels. In the pancreas, E2treatment had no significant effect on the levels of either PPSS II′ mRNA or PPSS II" mRNA. However, E2 treatment significantly ( P < 0.005) decreased levels of PPSS I mRNA. These data suggest that E2 acts, in part, to increase plasma growth hormone levels in rainbow trout by decreasing the endogenous inhibitory somatostatinergic tone by inhibiting plasma levels of both SS-14 and SS-25 and hypothalamic levels of mRNA encoding these proteins.
Nuclear factor-κB inhibitor peptide inhibits spontaneous and interleukin-1β-induced sleep
Authors: Kubota Takeshi , Kushikata Tetsuya , Fang Jidong , Krueger James M.
Published: December 2017

Nuclear factor-κB (NF-κB) is a transcription factor that when activated promotes production of several sleep-promoting substances such as interleukin-1β (IL-1β), tumor necrosis factor-α, and nerve growth factor. Therefore, we hypothesized that inhibition of NF-κB activation would attenuate sleep. A NF-κB cell-permeable inhibitor peptide (IP) was injected intracerebroventricularly (5 and 50 μg for rats, 100 μg for rabbits). On a separate day, time-matched control injections of a cell-permeable inactive control peptide were done in the same animals. The 50-μg dose of IP in rats and the 100-μg dose in rabbits significantly inhibited non-rapid eye movement sleep and rapid eye movement sleep if administered during the light period. Moreover, pretreatment of rabbits with 100 μg of the IP 12 h before intracerebroventricular injection of IL-1β (10 ng) significantly attenuated IL-1β-induced sleep and febrile responses. The current data support the hypothesis that a brain cytokine network is involved in sleep regulation and that NF-κB is a crucial factor in physiological sleep regulation.
A cortisol surge mediates the enhanced polyamine synthesis in porcine enterocytes during weaning
Authors: Wu Guoyao , Flynn Nick E. , Knabe Darrell A. , Jaeger Laurie A.
Published: December 2017

This study was conducted to determine whether a cortisol surge mediates the enhanced expression of intestinal ornithine decarboxylase (ODC) in weanling pigs. Piglets were nursed by sows until 21 days of age, when 40 pigs were randomly assigned into one of four groups (10 animals/group). Group 1continued to be fed by sows, whereas groups 2–4 were weaned to a corn and soybean meal-based diet. Weanling pigs received intramuscular injections of vehicle solvent (sesame oil), RU-486 (a potent blocker of glucocorticoid receptors; 10 mg/kg body wt), and metyrapone (an inhibitor of adrenal cortisol synthesis; 5 mg/kg body wt), respectively, 5 min before weaning and 24 and 72 h later. At 29 days of age, pigs were used to prepare jejunal enterocytes for ODC assay and metabolic studies. To determine polyamine (putrescine, spermidine, and spermine) synthesis, enterocytes were incubated for 45 min at 37°C in 2 ml Krebs-bicarbonate buffer containing 1 mM [U-14C]arginine, 1 mM [U-14C]ornithine, 1 mM [U-14C]glutamine, or 1 mM [U-14C]proline plus 1 mM glutamine. Weaning increased intestinal ODC activity by 230% and polyamine synthesis from ornithine, arginine, and proline by 72–157%. Arginine was a quantitatively more important substrate than proline for intestinal polyamine synthesis in weaned pigs. Administration of RU-486 or metyrapone to weanling pigs prevented the increases in intestinal ODC activity and polyamine synthesis, reduced intracellular polyamine concentrations, and decreased villus heights and intestinal growth. Our results demonstrate an essential role for a cortisol surge in enhancing intestinal polyamine synthesis during weaning, which may be of physiological importance for intestinal adaptation and remodeling.
Effect of locally applied drugs on the pH of luminal fluid in the endolymphatic sac of guinea pig
Authors: Couloigner Vincent , Teixeira Marie , Hulin Philippe , Sterkers Olivier , Bichara Maurice , Escoubet Brigitte , Planelles Gabrielle , Ferrary Evelyne
Published: December 2017

The aim of the present work was to assess the effect of various drugs applied locally on the pH of the luminal fluid (pHlum) in guinea pig endolymphatic sac. pHlum and transepithelial potential, when measured in vivo by means of double-barrelled pH-sensitive microelectrodes, were 7.06 ± 0.08 and +6.1 ± 0.34 mV (mean ± SE; n = 84), respectively, which is consistent with a net acid secretion in the luminal fluid of the endolymphatic sac. Bafilomycin and acetazolamide increased and decreased, respectively, pHlum. Amiloride, ethylisopropylamiloride, ouabain, and Schering 28080 had no effect on pHlum. Results obtained with inhibitors of anionic transport systems were inconclusive; e.g., DIDS reduced pHlum, whereas neither SITS nor triflocin had any effect. We conclude that bafilomycin-sensitive H+-ATPase activity accounts for the transepithelial acid gradient measured in the endolymphatic sac and that intracellular and membrane-bound carbonic anhydrase probably participates in regulating endolymphatic sac pHlum. The relationship between acid pH, endolymph volume, and Ménière's disease remains to be further investigated.