| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
INSERM U 317 and Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, 31073 Toulouse Cedex, France
1Correspondence: INSERM U317, Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, 37 Allées Jules Guesde, 31073 Toulouse Cedex, France. E-mail: galitzky{at}cict.fr
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
2-adrenergic and adenosine A1 agonists receptors) did
not change ANP- but suppressed isoproterenol-induced lipolysis. The
noninvolvement of the PDE-3B was finally confirmed by measuring its
activity under ANP stimulation. Thus, we demonstrate that natriuretic
peptides are a new pathway controlling human adipose tissue lipolysis
operating via a cGMP-dependent pathway that does not involve PDE-3B
inhibition and cAMP production.—Sengenès, C., Berlan, M., De
Glisezinski, I., Lafontan, M., Galitzky, J. Natriuretic peptides: a
new lipolytic pathway in human adipocytes.
Key Words: human fat cells • ANP • BNP • lipolysis • microdialysis
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
showed that
infusion of atrial tissue extracts in rats induced strong natriuresis.
The first member of the natriuretic family was discovered: atrial
natriuretic peptide (ANP). Subsequently two other natriuretic peptides
were isolated: brain natriuretic peptide (BNP) (2)
and
C-type natriuretic peptide (CNP) (3)
. Their biological
activities are mediated by specific receptors bearing a guanylyl
cyclase activity (NPr-A, NPr-B) or not (NPr-C). NPr-A and NPr-B are the
active receptors whereas NPr-C seems to be involved in clearance of the
peptide. Moreover, some studies have established that NPr-C might be
negatively coupled to adenylyl cyclase via a Gi protein (4
, 5)
. Natriuretic peptides are involved in the regulation of blood
pressure and blood volume. They inhibit renin, vasopressin, and
aldosterone release. They markedly stimulate diuresis and natriuresis
and are potent vasodilators.
ANP receptors have been identified in various tissues including
rat fat cells (6
7
8
9)
. Furthermore, some studies have shown
that human adipose tissue expresses natriuretic peptide receptor
messenger RNA (10)
. However, despite the presence of
natriuretic peptide receptors in rodent fat cells and ANP-induced
cyclic GMP (cGMP) production (6
7
8
, 11)
, no biological
responses have yet been reported for fat cells.
The aim of our work was to study the biological effect of natriuretic peptides in human adipose tissue. We demonstrate, for the first time, that atrial natriuretic peptide is a powerful lipolytic agent both in situ in human adipose tissue and in vitro isolated fat cells. ANP acts through guanylyl cyclase activation and cGMP production. However, its lipolytic effect does not involve phosphodiesterase (PDE) inhibition or cyclic AMP (cAMP) production.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Adipocyte preparation and lipolysis measurements
Isolated adipocytes were obtained according to the method of
Rodbell (12)
by collagenase digestion of adipose fragments
in Krebs Ringer bicarbonate buffer containing albumin (3.5 g/100 ml)
(KRBA) and glucose (6 mmol/l) at pH 7.4 and under gentle shaking at
around 60 cycles/min at 37°C. Then, the fat cells were filtered
through a silk screen and washed three times with KRBA buffer to
eliminate collagenase. Isolated adipocytes were brought to a suitable
dilution (2000–3000 cells/assay) in KRBA buffer for lipolysis assays
and incubated with pharmacological agents in a final volume of 100 µl
and for 90 min at 37°C. At the end of the incubation, 20 to 50 µl
aliquots of the infranatant were taken for glycerol determination
(13)
, which was used as the lipolytic index. Total lipid
was determined gravimetrically after solvent extraction.
Determination of cAMP and cGMP concentrations
Fat cells were preincubated in 1 ml of KRBA for 15 min at 37°C
in the presence of 0.1 mmol/l IBMX (nonspecific PDE inhibitor). Cells
were then further incubated for 10 min in the presence or absence of
0.1 µmol/l ANP or of 10 µmol/l forskolin (a specific adenylyl
cyclase activator). The reaction was stopped by addition of a solution
of chloroform, methanol, 1N HCl (2V/1V/0,1V). After centrifugation
(5000 rpm, 5 min), the aqueous phase of each sample was freeze-dried
and redissolved in ELISA buffer in order to measure cyclic nucleotide
content according to the kit manufacturer’s instructions (Cayman
Chemical Company, Ann Arbor, Mich.).
Radioligand binding assay
Isolated adipocytes were broken in a hypotonic lysing medium (5
mmol/l Tris pH 7.5, 5 mmol/l EDTA) containing several protease
inhibitors (100 µmol/l phenylmethylsulfonyl fluoride, 0.5 mg/ml
bacitracin, 1 µmol/l aprotinin, 10 µmol/l thiorphan). Then crude
adipocyte membranes were pelleted by centrifugation (48,000
g, 15 min at 4°C). The pellet was washed twice with 10 ml
of binding buffer [50 mmol/l Tris pH 7.5, 5 mM
MgCl2, 1% bovine serum albumin (BSA), 0.5 mg/ml
bacitracin, 1 µmol/l aprotinin, 10 µmol/l thiorphan]. The pellet
was finally resuspended in the same buffer at a final concentration of
1–2 mg of protein per milliliter and immediately used for binding
experiments. Assays were performed in a final volume of 400 µl
containing 100 µl membrane suspension, 100 µl
[125I]-ANP. Nonspecific binding was defined in
the presence of 1 µmol/l of unlabeled ANP. Saturation experiments
were carried out under constant shaking for 45 min at 25°C. The
incubation was stopped by centrifugation (13,000 g for 10
min). The pellet was washed twice with 500 µl of binding buffer and
the radioactivity was counted in a gamma counter.
Measurements of PDE-3B activity
Adipocytes were incubated in KRB (pH 7.4) in the presence of
insulin (0.1 µmol/l) (insulin was used for its potency to activate
adipocyte type III phosphodiesterase), OPC 3911 (10 µmol/l) (PDE-3B
specific inhibitor), or ANP (0.1 µmol/l) for 30 min at 37°C. The
reaction was stopped by addition of an equal volume of hypotonic buffer
(20 mmol/l Tris, 1 mmol/l EDTA pH 7.4) containing 1 complete mini
tablet of protease inhibitors per 10 ml. Cells were homogenized and
stored at -80°C until used. The day of the assay, cell homogenate
was centrifuged at 48,000 g for 20 min at 4°C. The pellet
was washed and rehomogeneized in TES buffer (10 mmol/l TES, 5 mmol/l
MgCl2 pH 7.4) and recentrifuged.
The membrane fraction (20–40 µg) was incubated for 15 min in a final volume of 100 µl of TES buffer containing 250 mmol/l sucrose, 0.5 µmol/l cAMP, 0.5 U/ml adenosine deaminase, 2% BSA, and ~100 000 dpm/assay of [3H]cAMP at 30°C in the presence or absence of 10 µmol/l OPC 3911 or 10 µmol/l IBMX (nonspecific PDE inhibitor). The reaction was stopped at 95°C for 2 min. Then 50 µl of Crotalux atrox snake venom (2 mg/ml) was added. Samples were further incubated for 20 min at 30°C. The reaction was stopped at 95°C for 2 min. Unreacted cAMP was removed by mixing samples with 500 µl of a 33% slurry of Dowex AG-1 x 2 (Bio-Rad, Hercules, Calif.). The mixture was shaken and centrifuged for 5 min at 15,000 g. Finally, 0.2 ml of the supernatant was removed and counted in 4 ml of scintillation liquid. PDE activities were expressed as picomoles of cAMP transformed per minute and per milligram of protein (determined using a Bio-Rad kit, DC protein assay). In our experimental conditions, PDE-3B activity represented 84.6 ± 4.16% of the total PDE activity present in the membrane fraction.
In vivo studies
Subjects
Seven lean men (mean age: 22.3±1.5 years) were involved in the
study. The mean body weight and body mass index of the subjects were
73.7 ± 5.3 kg (range: 70–81 kg) and 23.0 ± 1.6 kg/m2
(range: 21–25 kg/m2), respectively. All were drug-free and had a
stable weight for at least 3 months before the beginning of the study.
All subjects gave their written informed consent before the study. The
studies were performed according to the Declaration of Helsinki and
approved by the Ethical Committee of Toulouse University Hospital.
The subjects were investigated at 8 AM after an overnight
fast and were placed in a semirecumbent position. A microdialysis study
was performed as described previously (14)
. Briefly, a
microdialysis probe (Carnegie Medicine, Stockholm, Sweden) of 20 x 0.5 mm and 20,000 mol wt cutoff was inserted into the abdominal s.c.
adipose tissue (SCAT) and connected to a microinjection pump (Harvard
apparatus, S.A.R.L., Les Ulis, France). The probe was perfused with
Ringer solution (139.3 mmol/l sodium, 2.7 mmol/l potassium, 0.9 mmol/l
calcium, 140.5 mmol/l chloride, 2.4 mmol/l bicarbonate, and 5.6 mmol/l
glucose; B. BRAUN Medical SA, Boulogne, France) supplemented with
ethanol (1.7 g/l) in order to estimate local SCAT blood flow changes
(14)
. No outgoing dialysate was collected during the first
30 min after the implantation. The in vivo recovery rate was
then determined for each probe using measurement of dialysate glycerol
concentrations at various perfusion rates. This calibration procedure
has previously been described for the estimation of the interstitial
glycerol concentration in adipose tissue (14)
. Briefly,
the probes were perfused at four successive rates (0.8, 1.5, 2.5, and
3.5 µl/min), separated by appropriate washout periods, and glycerol
concentrations were determined in the dialysate for each perfusion
rate. Dialysate concentrations were plotted (after log transformation)
against the perfusion rates. Linear regression analysis was used to
calculate the glycerol concentration at zero flow, corresponding to the
interstitial glycerol concentration.
After this calibration period, the perfusion flow rate was maintained at 2.5 µl/min. Two 15 min fractions of the outgoing dialysate were collected for basal evaluations. After this, the probe was infused with initial perfusate solution supplemented with 10 µmol/l ANP. Collection of 15 min fractions was performed during 60 min of ANP infusion. During the last 60 min, the initial perfusate (without ANP) was infused and 15 min fractions of the dialysate were collected.
Drugs and chemicals
(-)Isoproterenol hydrochloride (nonselective ß-adrenergic
receptor agonist), R-(-)PIA (phenylisopropyladenosine, a specific
A1-adenosine receptor agonist), UK14304
(2-adrenergic receptor agonist), IBMX (nonselective
phosphodiesterase inhibitor), insulin, BSA (fraction V), and forskolin
were from Sigma-Aldrich (Saint Quentin Fallavier, France). OPC 3911
{N-cyclohexyl-N-2-hydroxyethyl-4(6-(1,2-dihydro-2-oxo-quinolyloxy))butyramide}
was kindly provided by Otsuka Pharmaceutical (Tokushima, Japan). Crude
collagenase, enzymes for glycerol assays and tablets of protease
inhibitors came from Boehringer Mannheim Corp. (Mannheim, Germany).
Human -ANP (1–28) and CNP (C-type natriuretic peptide) were from
Neosystem Laboratories (Strasbourg, France). Human BNP (1–32) came
from Novabiochem (France Biochem, Meudon, France). Bromo cGMP was from
Alexis Biochemicals (Coger SA, Paris, France). Human
3-[125I]-iodotyrosyl 28 (-ANP) was from
Amersham France (Les Ulis, France). For microdialysis experiments, the
human atrial natriuretic peptide was from Clinalpha (France Biochem).
Data analysis
Values are given as means ± SEM of
(n) separate experiments. Student’s paired t
tests were used for comparisons between matched pairs. Differences were
considered significant when P<0.05. The
concentration-response curves were fitted by nonlinear regression and
EC50 (half-maximal effective drug concentration)
calculated using the program Prism (GraphPad Software, San Diego,
Calif.).
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
. Spontaneous glycerol release (basal lipolysis), maximum
lipolytic effects, and calculated pD2 values for
isoproterenol, ANP, BNP, and CNP are given in Table 1
. In comparison with isoproterenol, ANP and BNP induced a strong
lipolytic effect; maximal values were similar to those obtained with
isoproterenol whereas CNP had a maximum effect corresponding only to
17.7% of that of isoproterenol. pD2 values gave
the relative rank order of potency: ANP > BNP >> CNP.
|
|
cGMP is classically considered to be the second messenger generated after natriuretic peptide receptor A or B (NPr-A or -B) activation. Bromo cGMP (a membrane-permeable cGMP analog) increased lipolysis (0.83±0.28 vs. 0.43±0.02 µmol glycerol/100 mg lipid; n=5, P<0.05); at 4 mmol/l, its effect represented 47.8 ± 13.2% of the maximal lipolytic effect initiated by the highest isoproterenol concentration.
In situ lipolytic effects of ANP
The effects of 10 µmol/l ANP on extracellular glycerol
concentration and on blood flow in SCAT are depicted in Fig. 1B
. The concentration of ANP was chosen because in
vitro experimentation using
[3-(125I)-iodotyrosyl 28] -ANP showed that
the recovery was ~5% (personal data). So it was expected that the
local ANP concentration in adipose tissue could reach a maximal
concentration around 0.5 µmol/l. A further dilution of ANP occurs in
the extracellular space, and the true concentration of ANP around the
receptor level was probably still lower. Due to the vasodilating effect
of ANP, the ethanol outflow/inflow ratio (expressed as a percentage,
i.e., the ethanol concentration measured in the dialysate divided by
the ethanol concentration measured in the perfusate x 100) was
lowered in the probe during ANP infusion. A significant effect was
observed within 15 min of infusion and the maximum effect was obtained
30 min after infusion. The ethanol ratio returned to preinfusion values
30 min after the cessation of the infusion. Simultaneously, the
extracellular glycerol concentration in SCAT increased significantly
within 30 min of ANP infusion; the maximum effect (~250%) being
observed after 45 min. Then the extracellular glycerol concentration
progressively decreased after the end of infusion and reached
preinfusion values after 45 min.
[125I]ANP binding studies on fat cell membranes
ANP receptors were quantified on human fat cell membrane
preparations by saturation experiments, using
[125I]ANP as a ligand. Specific binding of
[125I]ANP was saturable and of high affinity
(Fig. 2
). Nonspecific binding defined in the presence of 1 µmol/l of ANP
represented ~10% of the total radioactivity bound. Scatchard
analysis indicated a homogeneous population of
[125I]ANP binding sites with a
Kd value of 72.9 ± 16.0 pmol/l and a
Bmax value of 400 ± 38 fmol/mg protein
(n=5).
|
Intracellular cAMP and cGMP determination in fat cells
The effects of ANP on intracellular cyclic nucleotide formation
were investigated in the presence of IBMX. Basal intracellular cGMP and
cAMP were 0.98 ± 0.25 and 29.7 ± 2.1 pmol/100 mg lipid/10
min, respectively. In these conditions, forskolin (10 µmol/l) induced
an increase in cAMP level (191.8±33.6 pmol/100 mg lipid/10 min) but
did not modify the cGMP level (1.5±0.3 pmol/100 mg lipid/10 min). ANP
(0.1 µmol/l) potently increased (187-fold) the cGMP level
(183.7±68.3 pmol/100 mg lipid/10 min), whereas the cAMP level remained
unchanged (40.8±9.1 pmol/100 mg lipid).
Putative role of PDE-3B in ANP-induced lipolysis
The activity of type 3B phosphodiesterase (PDE-3B), the main
enzyme involved in cAMP degradation in the adipocyte, is known to be
inhibited by cGMP in acellular systems (15)
. To explore
the putative involvement of PDE-3B in ANP-induced lipolysis, in a first
set of studies human white fat cells were preincubated for 30 min at
37°C in KRBA containing 0.5 µmol/l OPC 3911, a potent and highly
specific inhibitor of PDE-3B. Adipocytes were then exposed to
increasing concentrations of ANP or isoproterenol. As shown in
Fig. 3
, OPC 3911 did not modify the ANP concentration-response curve
(pD2 were 9.29±0.24 and 9.51±0.30,
respectively), whereas the isoproterenol effect was potentiated as
assessed by the shift to the left of the concentration-response curve;
pD2 value was significantly (P<0.05)
increased from 7.70 ± 0.11 to 8.22 ± 0.12.
|
Since PDE-3B is known to be activated by insulin (16
, 17)
,
a second set of experiments was designed to compare ANP- (1 nmol/l) and
isoproterenol-induced (10 nmol/l) lipolysis after pretreatment (30 min)
of fat cells by 100 nmol/l insulin. As shown in Fig. 4A
, ANP exhibited similar lipolytic effects in control and
insulin-treated cells whereas isoproterenol-induced lipolysis was
significantly reduced (values were reduced from 49.5±7.6% of the
maximum isoproterenol effect to 7.6±7.6%) after insulin treatment.
|
In a third set of experiments, cAMP levels were pharmacologically
reduced through activation of Gi protein in fat cells using a mixture
of the 2-agonist UK 14304 (1 µmol/l) plus the adenosine agonist
phenylisopropyladenosine (1 µmol/l). In these conditions of potent
inhibition of adenylyl cyclase activity and of reduced cAMP levels, the
PDE-3B activity was expected to be strongly decreased. Preincubation of
adipocytes with the inhibitory mixture totally abolished the lipolytic
effect usually found with the PDE-3B inhibitor OPC 3911 (from 76.9±7.9
to 1.4±6.8% of the maximal isoproterenol effect) and decreased the
lipolytic effects of isoproterenol, but did not modify ANP-induced
lipolysis (Fig. 4B
).
Finally, PDE-3B activities in human adipocytes were determined in order
to evaluate the effect of ANP on low Km cAMP PDE.
The results are reported in Table 2
. PDE-3B activity was significantly higher when cells were treated with
insulin (0.1 µmol/l) and significantly lower when treated with OPC
3911 (10 µmol/l). PDE-3B activity was not modified in adipocytes
treated with ANP (0.1 µmol/l).
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Our data clearly show that natriuretic peptides can control human
adipocyte lipolysis. Their lipolytic effect represented 92.8 ±
1.4%, 84.5 ± 5.5%, 17.7 ± 3.4% of the maximal effect of
isoproterenol for ANP, BNP, and CNP, respectively (Table 1)
. Our
in vitro data show a statistical difference in glycerol
production between basal and in the presence of ANP
10-11 M. This result shows that ANP is lipolytic
at a concentration close to circulating ANP levels in humans (10 to 20
pmol/l). Moreover, as expected from the presence of NPr-A mRNA in human
adipocyte (10)
, we identify, using binding experiments
with [125I]ANP on membranes from isolated human
adipocytes, a single population of high-affinity ANP binding sites
(Fig. 2)
. According to the relative affinity of the different
natriuretic peptides for this site (reflected by the
pD2 values depicted in Table 1
), the ANP receptor
has the pharmacological profile of a Npr-A receptor (18
, 19)
. As expected for a guanylyl-cyclase-containing receptor, its
activation promotes a strong increase in intracellular cGMP in the
human adipocyte. The fact that ANP induced-lipolysis could be mimicked
with a cell-permeable analog of cGMP (bromo-cGMP) raised the question
of the target that can be activated by cGMP in adipocytes to lead to
hormone-sensitive lipase activation.
Generally, lipolysis in adipocytes is stimulated by hormones that
activate adenylyl cyclase, elevate cAMP, and activate cAMP-dependent
protein kinase, resulting in phosphorylation and activation of
hormone-sensitive lipase (HSL). The enzyme PDE-3B, the main one
involved in the degradation of cAMP in adipocyte, is known to be
inhibited by cGMP in acellular assays (15
16
17
, 20)
.
Inhibition of PDE-3B increases lipolysis; an ANP-induced cGMP
production could therefore inhibit PDE-3B. We therefore focused our
study on PDE-3B as a putative intermediate of the ANP lipolytic effect.
However, our results show that ANP-induced lipolysis was independent of
PDE-3B inhibition. Different data supported this point. First,
inhibition of PDE-3B activity with the specific inhibitor OPC 3911
(15
, 21)
, which significantly potentiates the lipolytic
effect of isoproterenol, was without effect on the lipolytic response
initiated by ANP (Fig. 3)
. Second, PDE-3B activation by insulin
(16
, 17)
led to inhibition of isoproterenol-induced
lipolysis, whereas a full lipolytic effect was conserved with ANP (Fig. 4A
). Third, since the substrate of PDE-3B is cAMP, we
compared isoproterenol- and ANP-induced lipolysis in the presence of a
mixture of agonists for fat cell 2-adrenergic
receptors and A1-adenosine receptors. These drugs exert potent
antilipolytic actions through inhibition of adenylyl cyclase activity
(22
23
24)
, reduction of cAMP formation, and consequently
PDE-3B substrate availability. In that context, the lipolytic effect of
ANP was still preserved whereas the isoproterenol-induced lipolysis was
strongly blunted (Fig. 4B
). Fourth, exposure of cells to ANP
did not change the cAMP levels whereas forskolin (as expected) did.
Finally, and to confirm our hypothesis, quantification of PDE-3B
activity in adipocytes exposed to ANP, insulin and OPC 3911 was
undertaken. Our data clearly show that ANP did not modify PDE-3B
activity whereas insulin activated it and OPC 3911 inhibited it. Thus,
we conclude that ANP promotes cGMP intracellular accumulation and
lipolysis independently of PDE-3B inhibition.
The activation of cGMP-dependent protein kinase (PKG) could represent
the key mechanism of the action of ANP in human adipocytes. Such a
potential role for PKG is consistent with previously described effects
of ANP observed in other systems (25
, 26)
.
Hormone-sensitive lipase, the sole enzyme able to catalyze triglyceride
hydrolysis in adipocyte, is known to be principally phosphorylated by a
cAMP-dependent protein kinase (27)
. However, some earlier
studies observed in acellular systems that HSL could also be
phosphorylated by a cGMP-dependent PKG (28)
. Taken
together, one can propose that ANP-induced lipolysis involves cGMP
generation and thus PKG activation, leading finally to the
phosphorylation and stimulation of the HSL. Further studies are needed
to completely delineate all the components involved in the activation
of ANP-dependent lipolytic cascade.
Until now, most of the pharmacological approaches of the
physiopathology of the human fat cell have focused their attention on
the adrenergic control of this cell. This was based on the fact that
norepinephrine and epinephrine are the two main hormones controlling
human adipocyte lipolysis through different adrenergic receptor
subtypes (29)
. However, Uehlinger et al. (30)
have described that ANP infusion increased NEFA levels in control
subjects. They attributed this result to a sympathetic nervous system
activation. Our data suggest that part of this lipid mobilization could
be due to a direct effect of ANP on human adipocyte. Finally, many
studies have shown the possible dysregulation of the adrenergic control
in adipose tissue lipolysis in obese subjects. The present finding of a
new control of lipolysis by natriuretic peptides in human adipose
tissue raises the question of the physiological role of this new
lipolytic pathway and its putative involvement in the development and
in the pathogenesis of obesity.
|
ACKNOWLEDGMENTS |
|---|
Received for publication August 18, 1999.
Revision received December 6, 1999.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
ke, R., Gke, B., Noll, B., Richter, G., Christoph-Fehmann, H., Arnold, R. (1989) Receptors for atrial natriuretic peptide on isolated rat adipocytes. Biomed. Res. 10,463-467
This article has been cited by other articles:
|
|
 |
|
  N. O. Belo, M. R. Sairam, and A. M. dos Reis Impairment of the Natriuretic Peptide System in Follitropin Receptor Knockout Mice and Reversal by Estradiol: Implications for Obesity-Associated Hypertension in Menopause Endocrinology, March 1, 2008; 149(3): 1399 - 1406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Polak, C. Moro, D. Bessiere, J. Hejnova, M. A. Marques, M. Bajzova, M. Lafontan, F. Crampes, M. Berlan, and V. Stich Acute exposure to long-chain fatty acids impairs {alpha}2-adrenergic receptor-mediated antilipolysis in human adipose tissue J. Lipid Res., October 1, 2007; 48(10): 2236 - 2246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Moro, F. Pillard, I. de Glisezinski, F. Crampes, C. Thalamas, I. Harant, M.-A. Marques, M. Lafontan, and M. Berlan Atrial natriuretic peptide contribution to lipid mobilization and utilization during head-down bed rest in humans Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R612 - R617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Polak, C. Moro, E. Klimcakova, M. Kovacikova, M. Bajzova, M. Vitkova, Z. Kovacova, R. Sotornik, M. Berlan, N. Viguerie, et al. The atrial natriuretic peptide- and catecholamine-induced lipolysis and expression of related genes in adipose tissue in hypothyroid and hyperthyroid patients Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E246 - E251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Gutkowska, A. Paquette, D. Wang, J.-M. Lavoie, and M. Jankowski Effect of exercise training on cardiac oxytocin and natriuretic peptide systems in ovariectomized rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R267 - R275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Richards Natriuretic Peptides: Update on Peptide Release, Bioactivity, and Clinical Use Hypertension, July 1, 2007; 50(1): 25 - 30. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Meirhaeghe, M. S. Sandhu, M. I. McCarthy, P. de Groote, D. Cottel, D. Arveiler, J. Ferrieres, C. J. Groves, A. T. Hattersley, G. A. Hitman, et al. Association between the T-381C polymorphism of the brain natriuretic peptide gene and risk of type 2 diabetes in human populations Hum. Mol. Genet., June 1, 2007; 16(11): 1343 - 1350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Aoyagi, J.-i. Birumachi, M. Hiroyama, Y. Fujiwara, A. Sanbe, J. Yamauchi, and A. Tanoue Alteration of Glucose Homeostasis in V1a Vasopressin Receptor-Deficient Mice Endocrinology, May 1, 2007; 148(5): 2075 - 2084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. McEntegart, B. Awede, M. C. Petrie, N. Sattar, F. G. Dunn, N. G. MacFarlane, and J. J.V. McMurray Increase in serum adiponectin concentration in patients with heart failure and cachexia: relationship with leptin, other cytokines, and B-type natriuretic peptide Eur. Heart J., April 2, 2007; (2007) ehm033v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Wang, M. G. Larson, M. J. Keyes, D. Levy, E. J. Benjamin, and R. S. Vasan Association of Plasma Natriuretic Peptide Levels With Metabolic Risk Factors in Ambulatory Individuals Circulation, March 20, 2007; 115(11): 1345 - 1353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Birkenfeld, M. Boschmann, C. Moro, F. Adams, K. Heusser, J. Tank, A. Diedrich, C. Schroeder, G. Franke, M. Berlan, et al. {beta}-Adrenergic and Atrial Natriuretic Peptide Interactions on Human Cardiovascular and Metabolic Regulation J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 5069 - 5075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Engeli, M. Boschmann, P. Frings, L. Beck, J. Janke, J. Titze, F. C. Luft, M. Heer, and J. Jordan Influence of Salt Intake on Renin-Angiotensin and Natriuretic Peptide System Genes in Human Adipose Tissue Hypertension, December 1, 2006; 48(6): 1103 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I J Bujalska, M Quinkler, J W Tomlinson, C T Montague, D M Smith, and P M Stewart Expression profiling of 11{beta}-hydroxysteroid dehydrogenase type-1 and glucocorticoid-target genes in subcutaneous and omental human preadipocytes. J. Mol. Endocrinol., October 1, 2006; 37(2): 327 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Malavazos, L. Morricone, A. Marocchi, F. Ermetici, B. Ambrosi, and M. M. Corsi N-terminal pro-B-type natriuretic Peptide and echocardiographic abnormalities in severely obese patients: correlation with visceral fat. Clin. Chem., June 1, 2006; 52(6): 1211 - 1213. [Full Text] [PDF]
|
|
|
|
|
|
C. Moro, J. Polak, J. Hejnova, E. Klimcakova, F. Crampes, V. Stich, M. Lafontan, and M. Berlan Atrial natriuretic peptide stimulates lipid mobilization during repeated bouts of endurance exercise Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E864 - E869. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Potter, S. Abbey-Hosch, and D. M. Dickey Natriuretic Peptides, Their Receptors, and Cyclic Guanosine Monophosphate-Dependent Signaling Functions Endocr. Rev., February 1, 2006; 27(1): 47 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nishikimi, N. Maeda, and H. Matsuoka The role of natriuretic peptides in cardioprotection Cardiovasc Res, February 1, 2006; 69(2): 318 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bionda, C. Bergerot, D. Ardail, C. Rodriguez-Lafrasse, and R. Rousson Plasma BNP and NT-proBNP Assays by Automated Immunoanalyzers: Analytical and Clinical Study Ann. Clin. Lab. Sci., January 1, 2006; 36(3): 299 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lafontan, C. Moro, C. Sengenes, J. Galitzky, F. Crampes, and M. Berlan An Unsuspected Metabolic Role for Atrial Natriuretic Peptides: The Control of Lipolysis, Lipid Mobilization, and Systemic Nonesterified Fatty Acids Levels in Humans Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2032 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kistorp, J. Faber, S. Galatius, F. Gustafsson, J. Frystyk, A. Flyvbjerg, and P. Hildebrandt Plasma Adiponectin, Body Mass Index, and Mortality in Patients With Chronic Heart Failure Circulation, September 20, 2005; 112(12): 1756 - 1762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. K. Antos, S. E. Abbey-Hosch, D. R. Flora, and L. R. Potter ATP-independent Activation of Natriuretic Peptide Receptors J. Biol. Chem., July 22, 2005; 280(29): 26928 - 26932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Birkenfeld, M. Boschmann, C. Moro, F. Adams, K. Heusser, G. Franke, M. Berlan, F. C. Luft, M. Lafontan, and J. Jordan Lipid Mobilization with Physiological Atrial Natriuretic Peptide Concentrations in Humans J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3622 - 3628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. McCord, B. J. Mundy, M. P. Hudson, A. S. Maisel, J. E. Hollander, W. T. Abraham, P. G. Steg, T. Omland, C. W. Knudsen, K. R. Sandberg, et al. Relationship Between Obesity and B-Type Natriuretic Peptide Levels Arch Intern Med, November 8, 2004; 164(20): 2247 - 2252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Filippatos, S. D. Anker, and F. Kardaras B-type natriuretic peptide serum levels in acute heart failure Eur. Heart J., June 2, 2004; 25(12): 1085 - 1085. [Full Text] [PDF]
|
|
|
|
|
|
G. H. Goossens, E. E. Blaak, W. H. M. Saris, and M. A. van Baak Angiotensin II-Induced Effects on Adipose and Skeletal Muscle Tissue Blood Flow and Lipolysis in Normal-Weight and Obese Subjects J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2690 - 2696. [Abstract] [Full Text] [PDF]
|
|
), BNP (
), and CNP (
) in human fat cells.
Lipolysis is expressed in percent maximum effect of isoproterenol.
Values are means ± SEM of 8 to 16 experiments.
B) Changes in ethanol ratio (ethanol dialysate
concentration/ethanol perfusate level x 100) and extracellular
glycerol concentrations in human s.c. adipose tissue during the
infusion of 10 µmol/l ANP in the probes. Values are means ±
SEM of 7 subjects. *Significantly different from basal
value.
