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expression in the hypothalamus
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060 - 0812, Japan
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Leptin is known to be an important
circulating signal for regulation of food intake and body weight.
Recent evidence has suggested that leptin is involved in infection and
inflammation. The afferent vagus nerve is known to be an important
component for transmitting peripheral immune signals to the brain, such
as interleukin (IL)-1
expression in the brain, anorexia, and fever
responses. In the present study, we investigated whether intravenous
leptin-induced IL-1 expression in the hypothalamus is mediated via
afferent vagus nerve. IL-1 transcripts in the hypothalamus were
significantly increased on RT-PCR assessment 1 h after the
administration of leptin (1 mg/kg iv) to mice. Subdiaphragmatic
vagotomy did not significantly modify intravenous leptin-induced
IL-1 expression in the hypothalamus compared with that in
sham-treated mice. These data suggest that circulating leptin directly
acts in the brain independently of afferent vagus nerve input
originating from the subdiaphragmatic organs.
afferent vagus nerve; immune-to-brain communication; inflammation
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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LEPTIN, the 16-kDa protein encoded by the ob gene (44), is known to be an important energy balance regulator through its actions in the hypothalamus, associating appetite and energy expenditure (9, 32). Leptin is mainly secreted by adipose tissue and released into circulation to act in both the periphery and the brain. Leptin enters the brain via a saturable transport mechanism (2) and is thought to activate primarily on the hypothalamic centers.
Increasing evidence has suggested that leptin may interact with
cytokines in the immune system. Intraperitoneal administration of
lipopolysaccharide (LPS) or cytokines such as interleukin (IL)-1 or
tumor necrosis factor (TNF) has been shown to increase leptin expression in serum and adipose tissue (16, 35).
Conversely, exogenous leptin has been shown to upregulate both
phagocytosis and the production of proinflammatory cytokines (TNF-
,
IL-6, and IL-12) in macrophages (26), and leptin increased
monocyte chemoattractant protein-1 expression in endothelial cells
(7). Moreover, it has been reported that leptin modulates
T-cell immune function (11, 27). LPS applied peripherally
increases IL-1 expression in the brain (12). A recent
report suggested that the effects of leptin on food intake and body
temperature were mediated by IL-1 in the hypothalamus
(28), and we reported that one of the target cells of the
leptin-induced IL-1 transcript in the brain may be glial cells
(22). These findings may lead us to hypothesize a
possibility that peripheral leptin functions as an afferent signal to
transmit peripheral immune signals in the brain. It was reported that
leptin activates afferent vagus nerve activity (40, 43).
The afferent vagus nerve is known to be an important component for
transmitting peripheral immune signals to the brain, such as IL-1
expression in the brain (18, 21, 25), stimulation of the
hypothalamic-pituitary-adrenal (HPA) axis (13), anorexia,
and fever responses (6, 8, 37). However, there is
inconsistent evidence showing that vagotomy does not block suppression
of food intake induced by the peripheral application of LPS or IL-1
(33, 36). Therefore, using subdiaphragmatic vagotomized
mice, we investigated whether intravenous leptin-induced IL-1
transcript in the brain is mediated via afferent vagus nerve activity.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Animals. C57BL/KsJ mice were obtained at 7 wk old from Central Laboratories for Experimental Animals (Japan). Mice were maintained in a room at 22-24°C under a constant day-night rhythm and were given food and water ad libitum. All animal experiments were carried out in accordance with the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals and were approved by the animal care and use committee at Hokkaido University.
Surgical preparations. The procedure for bilateral subdiaphragmatic vagotomy or sham surgery was adapted from that described previously (18). Mice were anesthetized with pentobarbital sodium (50 mg/kg ip). The stomach and lower esophagus were visualized from an upper midline laparotomy. The stomach was gently retracted down beneath the diaphragm to clearly expose both vagal trunks. At least 1 cm of the visible vagal nerves was dissected. In addition, all neural and connective tissues surrounding the esophagus immediately beneath the diaphragm were removed to transect all small vagal branches. For sham-operated animals, the vagus nerves were similarly exposed but not cut.
Three weeks after either vagotomy or sham surgery, the completeness of vagotomy was assessed. This test is based on the satiety effect of cholecystokinin-octapeptide (CCK-8; Peptide Institute, Japan), which is known to be mediated by the vagus nerve (39). Mice were injected with saline or CCK-8 (8 µg/kg ip) after food deprivation from 0930 to 1830. Five minutes after saline or CCK-8 application, food intake was measured for 30 min in both vagotomized and sham-operated mice. Two days were allowed between the saline and CCK-8 injections. The animals were then allowed at least 1 additional week recovery period. After the experiment, the wet weight of the stomach was measured after removing residual gastric contents.Leptin injection and sample preparation.
Mice were given food and water ad libitum before the leptin injection.
Murine leptin (Pepro Tech, London) was dissolved in saline, and all
injections were administered intravenously (1 mg/kg) via the tail vein
and delivered at an injection volume of 5 ml/kg. One hour after leptin
injection, mice were killed by decapitation, and the brain was quickly
removed. The hypothalamus was rapidly dissected out on an ice-cold
plate. The samples were then snap-frozen in liquid nitrogen and stored
at 
80°C.
RT-PCR.
Total RNA was isolated using TRI REAGENT (Sigma). cDNA was synthesized
from 2 µg of total RNA by reverse transcription using 100 U of
Superscript RT (GIBCO BRL) and oligo(dT)12-18 primer (GIBCO BRL) in a 20-µl reaction containing 1× Superscript buffer (GIBCO BRL), 1 mM dNTP mix, 10 mM dithiothreitol, and 40 U of RNase
inhibitor. Total RNA and oligo(dT)12-18 primer were incubated at 70°C for 10 min before the reverse transcription. After
incubation for 1 h at 42°C, the reaction was terminated by a
denaturing enzyme for 15 min at 70°C. For PCR amplification, 1.2 µl
of cDNA was added to 12 µl of a reaction mix containing 0.2 µM of
each primer, 0.2 mM of dNTP mix, 0.6 U of Taq polymerase, and 1× reaction buffer. PCR was performed in a DNA thermal cycler (Perkin-Elmer 2400-R). Primers used were as follows: IL-1 upstream, 5'-aat ctc aca gca gca cat caa-3'; IL-1 downstream, 5'-agc cca tac
ttt agg aag aca-3'; glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
upstream, 5'-aaa ccc atc acc atc ttc cag-3'; and GAPDH downstream,
5'-agg ggc cat cca cag tct tct-3'. The PCR products (10 µl) were
resolved by electrophoresis in an 8% polyacrylamide gel in 1×
Tris-borate, EDTA buffer. The gel was stained with ethidium bromide, and the gels were photographed under ultraviolet light. Band
densities were obtained using NIH Image 1.61 software.
mRNAs in the different experimental groups, the amount of
IL-1 mRNA in each structure studied was estimated as the ratio
IL-1/GAPDH.
Statistics. Results were expressed as means ± SE. Statistical analysis was performed with Student's t-test.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Verification of vagotomy.
Four weeks after subdiaphragmatic vagotomy, the body weight of
vagotomized mice did not differ significantly from that of sham-operated mice (24.9 ± 0.59 and 25.3 ± 0.91 g,
respectively). To assess the completeness of vagotomy, food intake
analysis was performed. Food intake was significantly decreased by 61%
in CCK-8-injected (8 µg/kg ip, 30 min) sham-operated mice compared
with those animals that received saline (Fig.
1A). Subdiaphragmatic vagotomy
abolished the satiety effect of CCK-8 compared with sham-operated mice
(Fig. 1A). Moreover, CCK-8 did not significantly decrease
food intake in vagotomized mice compared with the saline-injected
animals (Fig. 1A). Furthermore, we also measured stomach
weight to verify vagotomy as reported previously (5).
Stomach weight in vagotomized mice showed a 2.1-fold increase compared
with that of sham-operated mice (Fig. 1B). The stomach
weight of the sham-operated and vagotomized mice was 0.17 ± 0.01 g (n = 6) and 0.35 ± 0.05 g
(n = 6), respectively.
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Effect of vagotomy on intravenous leptin-induced IL-1
transcription in the hypothalamus.
Leptin (1 mg/kg iv, 1 h) was applied to sham-operated or
vagotomized mice, and IL-1 expression in the hypothalamus was
measured. IL-1 transcripts in the hypothalamus were significantly
increased 1 h after the application of leptin (1 mg/kg iv) in
sham-operated mice (see Fig. 3). The effect of leptin was not due to
endotoxin contamination because heat-inactivated leptin (5 mg/kg,
98°C, 30 min) did not induce an increase in IL-1 mRNA expression
in the hypothalamus (Fig. 2).
Subdiaphragmatic vagotomy did not significantly modify the intravenous
leptin-induced IL-1 expression compared with the sham-operated mice
(Fig. 3). Thus leptin may act in the brain and directly induce IL-1 expression independently of the afferent vagus nerve.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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It is becoming well accepted that the peripheral immune system can
signal the brain during inflammation. Peripheral administration of LPS
increases IL-1 expression in the brain (1, 20). Moreover, peripheral or central application of cytokines such as IL-1 induces fever (24), inhibition of food intake (29)
and gastric acid secretion (42), and activation of the
sympathetic (30) and HPA axis (4, 34). The
precise mechanisms by which IL-1 signals the brain are unknown, but
several mechanisms have been proposed. These mechanisms include
1) direct entry of IL-1 into the brain across the
blood-brain barrier by a saturable transport mechanism (3), 2) interaction of IL-1 with
circumventricular organs (organum vasculosum of the lamina terminalis,
area postrema, etc.) that lack the blood-brain barrier
(23), and 3) activation of afferent neurons of
the vagus nerve (41).
Increasing evidence has suggested that the vagus nerve is an important
pathway for cytokine-to-brain communication. IL-1 immunoreactivity was expressed in dendritic cells and macrophages within connective tissues associated with the abdominal vagus after
intraperitoneal injection of LPS (14), and systemic
application of IL-1 increases electrical activity of vagal afferent
nerves (10, 31). Furthermore, subdiaphragmatic vagotomy
has blocked or attenuated IL-1 expression in the brain (18,
25), stimulation of the HPA axis (13), and anorexia
and fever responses (6, 8, 37) induced by peripheral
IL-1 or LPS. Moreover, the selective transection of hepatic vagus
nerve effectively inhibited a pyrogenic response induced by LPS
(38). We previously reported that direct electrical
stimulation of afferent vagus nerve induces IL-1 expression in the
brain (21).
Recent evidence has suggested that leptin is involved in the immune
system (7, 11, 26, 27). Peripheral administration of LPS
or cytokines has been shown to increase leptin expression in serum and
adipose tissue (16, 35). Furthermore, peripheral leptin
induces IL-1 expression in the brain (22, 28). It was
reported that leptin activates the afferent vagus nerve in an in vitro
experiment (40, 43). Therefore, we examined whether intravenous leptin-induced IL-1 induction is mediated through the
activated vagal afferent nerve. In the present study, subdiaphragmatic vagotomy did not inhibit intravenous leptin-induced IL-1 expression in the hypothalamus. This finding suggests that leptin may directly induce the IL-1 transcript in the hypothalamus independently of
vagal afferent nerve activity. Leptin enters the brain across the
blood-brain barrier (2, 15), and it was recently
postulated that such transport occurs through the Ob-Ra receptor
(19). Herein, we propose that the afferent signal for
IL-1 induction in the brain during peripheral inflammation may
partly be mediated by the direct action of leptin in the brain.
Perspectives
It was reported that subdiaphragmatic vagotomy failed to block suppression of food intake induced by the peripheral application of LPS or IL-1 (33, 36). Hansen et al. (17)
suggested that low-dose IL-1-induced fever is dependent on vagal
afferent nerves, and high-dose IL-1-mediated fever may be dependent
on a blood-borne route. One of the possible explanations for these
observations is that unknown humoral factor(s) may contribute to
transmit signals to the brain independently of afferent vagus nerve
activity. It was reported that the effects of leptin on food intake and
body temperature may be mediated by IL-1 in the hypothalamus
(28). In the present study, we have shown that peripheral
leptin increases IL-1 expression in the hypothalamus independently
of the afferent vagus nerve. Herein, we propose that one of the unknown
humoral factor(s) involved in the afferent signal for IL-1 induction in the brain during peripheral inflammation may partly be mediated by leptin.
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ACKNOWLEDGEMENTS |
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This research was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture, Japan (to Y. Okuma and Y. Nomura) and by Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists (to T. Hosoi).
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FOOTNOTES |
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Address for reprint requests and other correspondence: Y. Okuma, Dept. of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido Univ., Sapporo 060-0812, Japan (E-mail: okumay{at}pharm.hokudai.ac.jp).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
10.1152/ajpregu.00549.2001
Received 7 September 2001; accepted in final form 30 October 2001.
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REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Ban, E,
Haour F,
and
Lenstra R.
Brain interleukin 1 gene expression induced by peripheral lipopolysaccharide administration.
Cytokine
4:
48-54,
1992[Web of Science][Medline].
2.
Banks, WA,
Kastin AJ,
Huang W,
Jaspan JB,
and
Maness LM.
Leptin enters the brain by a saturable system independent of insulin.
Peptides
17:
305-311,
1996[Web of Science][Medline].
3.
Banks, WA,
Ortiz L,
Plotkin SR,
and
Kastin AJ.
Human interleukin (IL)-1, murine IL-1 and murine IL-1 are transported from blood to brain in the mouse by a shared saturable mechanism.
J Phamacol Exp Ther
259:
988-996,
1991
4.
Berkenbosch, F,
van Oers J,
del Rey A,
Tilders F,
and
Besedovsky H.
Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1.
Science
238:
524-526,
1987
5.
Bluthé, RM,
Michaud B,
Kelley KW,
and
Dantzer R.
Vagotomy attenuates behavioural effects of interleukin-1 injected peripherally but not centrally.
Neuroreport
7:
1485-1488,
1996[Web of Science][Medline].
6.
Bluthé, RM,
Walter V,
Parnet P,
Layé S,
Lestage J,
Verrier D,
Poole S,
Stenning BE,
Kelley KW,
and
Dantzer R.
Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism.
C R Acad Sci III
317:
499-503,
1994[Medline].
7.
Bouloumie, A,
Marumo T,
Lafontan M,
and
Busse R.
Leptin induces oxidative stress in human endothelial cells.
FASEB J
13:
1231-1238,
1999
8.
Bret-Dibat, JL,
Bluthé RM,
Kent S,
Kelley KW,
and
Dantzer R.
Lipopolysaccharide and interleukin-1 depress food-motivated behavior in mice by a vagal-mediated mechanism.
Brain Behav Immun
9:
242-246,
1995[Web of Science][Medline].
9.
Campfield, LA,
Smith FJ,
Guisez Y,
Devos R,
and
Burn P.
Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks.
Science
269:
546-549,
1995
10.
Ek, M,
Kurosawa M,
Lundeberg T,
and
Ericsson A.
Activation of vagal afferents after intravenous injection of interleukin-1: role of endogenous prostaglandins.
J Neurosci
18:
9471-9479,
1998
11.
Faggioni, R,
Jones-Carson J,
Reed DA,
Dinarello CA,
Feingold KR,
Grunfeld C,
and
Fantuzzi G.
Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: role of tumor necrosis factor- and IL-18.
Proc Natl Acad Sci USA
97:
2367-2372,
2000
12.
Gabellec, MM,
Griffais R,
Fillion G,
and
Haour F.
Expression of interleukin 1, interleukin 1, and interleukin 1 receptor antagonist mRNA in mouse brain: regulation by bacterial lipopolysaccharide (LPS) treatment.
Brain Res Mol Brain Res
31:
122-130,
1995[Medline].
13.
Gaykema, RPA,
Dijkstra I,
and
Tilders FJH
Subdiaphragmatic vagotomy suppresses endotoxin-induced activation of hypothalamic corticotropin-releasing hormone neurons and ACTH secretion.
Endocrinology
136:
4717-4720,
1995[Abstract].
14.
Goehler, LE,
Gaykema RP,
Nguyen KT,
Lee JE,
Tilders FJ,
Maier SF,
and
Watkins LR.
Interleukin-1 in immune cells of the abdominal vagus nerve: a link between the immune and nervous systems?
J Neurosci
19:
2799-2806,
1999
15.
Golden, PL,
Maccagnan TJ,
and
Pardridge WM.
Human blood-brain barrier leptin receptor. Binding and endocytosis in isolated human brain microvessels.
J Clin Invest
99:
14-18,
1997[Web of Science][Medline].
16.
Grunfeld, C,
Zhao C,
Fuller J,
Pollack A,
Moser A,
Friedman J,
and
Feingold KR.
Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters.
J Clin Invest
97:
2152-2157,
1996[Web of Science][Medline].
17.
Hansen, MK,
O'Connor KA,
Goehler LE,
Watkins LR,
and
Maier SF.
The contribution of the vagus nerve in interleukin-1-induced fever is dependent on dose.
Am J Physiol Regulatory Integrative Comp Physiol
280:
R929-R934,
2001
18.
Hansen, MK,
Taishi P,
Chen Z,
and
Krueger JM.
Vagotomy blocks the induction of interleukin-1 (IL-1) mRNA in the brain of rats in response to systemic IL-1.
J Neurosci
18:
2247-2253,
1998
19.
Hileman, SM,
Tornoe J,
Flier JS,
and
Bjorbaek C.
Transcellular transport of leptin by the short leptin receptor isoform ObRa in Madin-Darby canine kidney cells.
Endocrinology
141:
1955-1961,
2000
20.
Hillhouse, EW,
and
Mosley K.
Peripheral endotoxin induces hypothalamic immunoreactive interleukin-1 in the rat.
Br J Pharmacol
109:
289-290,
1993[Web of Science][Medline].
21.
Hosoi, T,
Okuma Y,
and
Nomura Y.
Electrical stimulation of afferent vagus nerve induces IL-1 expression in the brain and activates HPA axis.
Am J Physiol Regulatory Integrative Comp Physiol
279:
R141-R147,
2000
22.
Hosoi, T,
Okuma Y,
and
Nomura Y.
Expression of leptin receptors and induction of IL-1 transcript in glial cells.
Biochem Biophys Res Commun
273:
312-315,
2000[Web of Science][Medline].
23.
Katsuura, G,
Arimura A,
Koves K,
and
Gottschall PE.
Involvement of organum vasculosum of lamina terminalis and preoptic area in interleukin 1-induced ACTH release.
Am J Physiol Endocrinol Metab
258:
E163-E171,
1990
24.
Kluger, MJ.
Fever: the role of pyrogens and cryogens.
Physiol Rev
71:
93-127,
1991[Abstract].
25.
Layé, S,
Bluthé RM,
Kent S,
Combe C,
Médina C,
Parnet P,
Kelley K,
and
Dantzer R.
Subdiaphragmatic vagotomy blocks induction of IL-1 mRNA in mice brain in response to peripheral LPS.
Am J Physiol Regulatory Integrative Comp Physiol
268:
R1327-R1331,
1995.
26.
Loffreda, S,
Yang SQ,
Lin HZ,
Karp CL,
Brengman ML,
Wang DJ,
Klein AS,
Bulkley GB,
Bao C,
Noble PW,
Lane MD,
and
Diehl AM.
Leptin regulates proinflammatory immune responses.
FASEB J
12:
57-65,
1998
27.
Lord, GM,
Matarese G,
Howard JK,
Baker RJ,
Bloom SR,
and
Lechler RI.
Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression.
Nature
394:
897-901,
1998[Medline].
28.
Luheshi, GN,
Gardner JD,
Rushforth DA,
Loudon AS,
and
Rothwell NJ.
Leptin actions on food intake and body temperature are mediated by IL-1.
Proc Natl Acad Sci USA
96:
7047-7052,
1999
29.
McCarthy, DO,
Kluger MJ,
and
Vander AJ.
Suppression of food intake during infection: is interleukin-1 involved?
Am J Clin Nutr
42:
1179-1182,
1985
30.
Murakami, Y,
Yokotani K,
Okuma Y,
and
Osumi Y.
Nitric oxide mediates central activation of sympathetic outflow induced by interleukin-1 in rats.
Eur J Pharmacol
317:
61-66,
1996[Web of Science][Medline].
31.
Niijima, A.
The afferent discharges from sensors for interleukin 1 in the hepatoportal system in the anesthetized rat.
J Auton Nerv Syst
61:
287-291,
1996[Web of Science][Medline].
32.
Pelleymounter, MA,
Cullen MJ,
Baker MB,
Hecht R,
Winters D,
Boone T,
and
Collins F.
Effects of the obese gene product on body weight regulation in ob/ob mice.
Science
269:
540-543,
1995
33.
Porter, MH,
Hrupka BJ,
Langhans W,
and
Schwartz GJ.
Vagal and splanchnic afferents are not necessary for the anorexia produced by peripheral IL-1, LPS, and MDP.
Am J Physiol Regulatory Integrative Comp Physiol
275:
R384-R389,
1998
34.
Sapolsky, R,
Rivier C,
Yamamoto G,
Plotsky P,
and
Vale W.
Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor.
Science
238:
522-524,
1987
35.
Sarraf, P,
Frederich RC,
Turner EM,
Ma G,
Jaskowiak NT,
Rivet DJ, III,
Flier JS,
Lowell BB,
Fraker DL,
and
Alexander HR.
Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia.
J Exp Med
185:
171-175,
1997
36.
Schwartz, GJ,
Plata-Salamán CR,
and
Langhans W.
Subdiaphragmatic vagal deafferentation fails to block feeding-suppressive effects of LPS and IL-1 in rats.
Am J Physiol Regulatory Integrative Comp Physiol
273:
R1193-R1198,
1997
37.
Sehic, E,
and
Blatteis CM.
Blockade of lipopolysaccharide-induced fever by subdiaphragmatic vagotomy in guinea pigs.
Brain Res
726:
160-166,
1996[Web of Science][Medline].
38.
Simons, CT,
Kulchitsky VA,
Sugimoto N,
Homer LD,
Szekely M,
and
Romanovsky AA.
Signaling the brain in systemic inflammation: which vagal branch is involved in fever genesis?
Am J Physiol Regulatory Integrative Comp Physiol
275:
R63-R68,
1998
39.
Smith, GP,
Jerome C,
Cushin BJ,
Eterno R,
and
Simansky KJ.
Abdominal vagotomy blocks the satiety effect of cholecystokinin in the rat.
Science
213:
1036-1037,
1981
40.
Wang, YH,
Taché Y,
Sheibel AB,
Go VLW,
and
Wei JY.
Two types of leptin-responsive gastric vagal afferent terminals: an in vitro single-unit study in rats.
Am J Physiol Regulatory Integrative Comp Physiol
273:
R833-R837,
1997
41.
Watkins, LR,
Maier SF,
and
Goehler LE.
Cytokine-to-brain communication: a review and analysis of alternative mechanisms.
Life Sci
57:
1011-1026,
1995[Web of Science][Medline].
42.
Yokotani, K,
Okuma Y,
and
Osumi Y.
Recombinant interleukin-1 inhibits gastric acid secretion by activation of central sympatho-adrenomedullary outflow in rats.
Eur J Pharmacol
279:
233-239,
1995[Web of Science][Medline].
43.
Yuan, CS,
Attele AS,
Wu JA,
Zhang L,
and
Shi ZQ.
Peripheral gastric leptin modulates brain stem neuronal activity in neonates.
Am J Physiol Gastrointest Liver Physiol
277:
G626-G630,
1999
44.
Zhang, Y,
Proenca R,
Maffei M,
Barone M,
Leopold L,
and
Friedman JM.
Positional cloning of the mouse obese gene and its human homologue.
Nature
372:
425-432,
1994[Medline].
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