help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Saint-Marc, P.
Right arrow Articles by Negrel, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saint-Marc, P.
Right arrow Articles by Negrel, R.
Endocrinology Vol. 142, No. 1 487-492
Copyright © 2001 by The Endocrine Society

ARTICLES

Angiotensin II as a Trophic Factor of White Adipose Tissue: Stimulation of Adipose Cell Formation1

Perla Saint-Marc, Leslie P. Kozak, Gérard Ailhaud, Christian Darimont2 and Raymond Negrel

Institut de Recherches Signalisation, Biologie du Développement et Cancer, Laboratoire Biologie du Développement du Tissu Adipeux, Centre de Biochimie, Unité Mixte de Recherches 6543, Centre National de la Recherche Scientifique, Université de Nice-Sophia Antipolis, Faculté des Sciences (P.S.-M., G.A., R.N.), 06108 Nice, France; and Pennington Biomedical Research Center, Louisiana State University (L.P.K.), Baton Rouge, Louisiana 70808-4124

Address all correspondence and requests for reprints to: Prof. Gérard Ailhaud, Institute of Signaling, Developmental Biology, and Cancer Research, Laboratory Biology of Adipose Tissue Development, Centre de Biochimie, Unité Mixte de Recherches 6543, Centre National de la Recherche Scientifique, Université de Nice-Sophia Antipolis, Faculté des Sciences, Parc Valrose, 06108 Nice Cedex 2, France. E-mail: ailhaud{at}unice.fr


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
White adipose tissue is known to contain the components of the renin-angiotensin system giving rise to angiotensin II (AngII). In vitro, prostacyclin is synthesized from arachidonic acid through the activity of cyclooxygenases 1 and 2 and is released from AngII-stimulated adipocytes. Prostacyclin, in turn, is able to favor adipocyte formation. Based upon in vivo and ex vivo experiments combined to immunocytochemical staining of glycerol-3-phosphate dehydrogenase (GPDH), an indicator of adipocyte formation, it is reported herein that AngII favors the appearance of GPDH-positive cells. In the presence of a cyclooxygenase inhibitor, this adipogenic effect is abolished, whereas that of (carba)prostacyclin, a stable analog of prostacyclin that bypasses this inhibition, appears unaltered. Taken together, these results are in favor of AngII acting as a trophic factor implicated locally in adipose tissue development. It is proposed that AngII enhances the formation of GPDH-expressing cells from preadipocytes in response to prostacyclin released from adipocytes.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
WHITE ADIPOSE tissue (WAT) is known as an important organ of angiotensinogen production. Angiotensinogen is expressed and released by mature white fat cells from rodents and humans. This observation is consistent with the differentiation-dependent expression of angiotensinogen in cells of preadipocyte clonal lines 3T3-F442A, 3T3-L1, and Ob1771 cells (1, 2, 3, 4, 5). Differentiated adipose cells from these clonal lines are aneuploid, but exhibit most, if not all, of the characteristics of mature fat cells (6). White adipose tissue and adipocytes contain the components of the renin-angiotensin system giving rise to angiotensin II (AngII) from angiotensinogen (7, 8, 9, 10, 11, 12). A role of AngII in adipose tissue development is suggested from several in vitro observations: 1) AngII is present in the culture medium of 3T3-F442A adipocytes (12); 2) regarding the AngII receptor, the AT1 and AT2 receptor subtypes have been characterized as the major species in rat and mouse adipocytes, respectively (13, 14); and 3) AngII is able, by means of binding to a receptor of the AT2 subtype present in mouse Ob1771 adipocytes, to trigger the release of prostacyclin. Prostacyclin, in turn, is able to promote in vitro the formation of new fat cells from Ob1771 preadipocytes through a paracrine mode of action (15).

We have also reported that prostacyclin, under the form of its stable analog (carba)prostacyclin, is a potent adipogenic hormone. (Carba)prostacyclin is active within a critical time window during preadipocyte differentiation, consistent with the presence of cell surface prostacyclin IP receptor in preadipocytes and its disappearance in adipocytes (16, 17, 18). The potency of (carba)prostacyclin is probably due to its ability to bind both to the cell surface IP receptors and to a nuclear receptor of the family of peroxisome proliferator-activated receptor, i.e. PPAR{delta}. First, activation of IP receptor by specific agonists i.e. prostacyclin, (carba)prostacyclin, PGE1, and BMY45778, regulates the expression of early transcription factors of the family of CCAAT/enhancer-binding proteins, i.e. C/EBPß and C/EBP{delta} (19). Second, like (carba)prostacyclin (20), it is assumed that prostacyclin binds to PPAR{delta} and acts at the gene level, as (carba)prostacyclin up-regulates at a transcriptional level the expression of the genes encoding cytosolic adipocyte fatty acid-binding protein, mitochondrial uncoupling protein-2, and secreted angiotensinogen in Ob1771 cells (21). In contrast to (carba)prostacyclin and prostacyclin, this gene effect is not mimicked by the other specific ligands of cell surface IP receptors (21, 22). Collectively, these in vitro observations emphasize the role played by AngII via prostacyclin in adipocyte differentiation and suggest its role in adipose tissue development, consistent with the results of microdialysis of rat epididymal fat pads, which showed a specific 3-fold increase in prostacyclin release for 30 min after AngII perfusion (23). In the studies presented herein, the formation of new fat cells after exposure to AngII or (carba)prostacyclin was examined in rat epididymal fat pads both in vivo and ex vivo. This formation was examined by determining the number of cells expressing glycerol-3-phosphate dehydrogenase (GPDH), a well known indicator of adipocyte formation. GPDH has been reported to be expressed during the differentiation of preadipose to adipose cells and is required in vitro for triacylgycerol accumulation (6). In vivo, this accumulation takes place immediately after GPDH emergence in differentiating adipose cells (24).


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Animals
Male BALB/cBy homozygous GPDH+/+ (wild-type) mice at 5–6 weeks of age were used. A second mouse strain not expressing GPDH was used as a control, e.g. homozygous GPDH-/- BALB/cHeA mice. Adipose tissue and other characteristics of these mutant mice appeared normal, suggesting the occurrence of alternate pathways of triacylglycerol synthesis (25). A third mouse strain was used, e.g. transgenic mice overexpressing GPDH on the GPDH-null background of BALB/cHeA mice. These mice exhibited hypertrophy of brown adipose tissue and reduction of white adipose tissue (26). GPDH activities of white fat tissue of wild-type BALB/cBy, GPDH-null BALB/cHeA mice, and transgenic BALB/cHeA mice were in the range of 940, 6, and 45,000 mU/mg, respectively (25, 26). Mice from the different strains and male Wistar rats (Charles River Laboratories, Inc., St Aubin-Les-Elbeuf, France) were used after being kept at a constant temperature of 22 C with a 12-h dark, 12-h light cycle. All animals had free access to water and a standard chow-low fat diet (UAR, Epinay-sur-Orge, France).

In vivo experiments
Rats were anesthetized at 0900 h, and microdialysis of epididymal fat pads was performed as previously described (23). Perfusion was carried out for 5 h in the presence of a stable analog of prostacyclin, e.g. (carba)prostacyclin at 10 µM in Ringer’s solution, whereas the contralateral pad was used as an internal control in the presence of Ringer’s solution alone. Then, approximately 300 mg of each pad surrounding the microdialysis probe were removed for isolation of stromal-vascular cells.

Ex vivo experiments
Male Wistar rats (220–250 g) were kept as described above. Epididymal fat pads were removed and rinsed in PBS, pH 7.4, chopped into approximately 10-mm3 pieces, and transferred into 60-mm culture dishes containing 5 ml DMEM/H16 medium (1/1, vol/vol) supplemented with 850 nM insulin, 0.2 nM T3, 10 µg/ml transferrin, 100 µM sodium ascorbate, and 20 nM sodium selenite in the absence or presence of 1 µM AngII or 1 µM (carba)prostacyclin, without or with 100 µM aspirin. Twenty hours later, adipose tissue fragments were digested with collagenase at 37 C, and stromal-vascular cells were isolated by centrifugation as previously described (27).

Cultured cells
Cells were cultured on 13-mm glass coverslips at the bottom of 24-mm wells in 12-well plastic plates. Stromal-vascular cells isolated directly from mouse epididymal fat pads or stromal-vascular cells isolated from adipose tissue fragments of rat epididymal fat pads after collagenase treatment were maintained for 2 days in DMEM/H16 medium containing 850 nM insulin, 0.2 nM T3, and 10 µg/ml transferrin (ITT medium) before immunostaining (27). Ob1771 cells were grown in the presence of 8% FCS. At confluence, cells were shifted to ITT medium supplemented with 1 µM (carba)prostacyclin for the indicated time period before immunostaining.

Fluorescence microscopy
Two-day cultured stromal-vascular cells were rinsed briefly at 37 C with PBS (pH 7.4), fixed and permeabilized with acetone/methanol mixture (30:70, vol/vol) for 5 min at -20 C, washed twice in PBS, and processed. Permeabilized cells were subsequently incubated at 20 C first in 1 ml PBS containing 3% BSA for 30 min and then in a humid atmosphere in the presence of anti-GPDH Igs as primary antibodies for 1 h (1:500 dilution in a final volume of 0.04 ml/coverslip). After washing in PBS, cells were stained for immunodetection first in 1 ml PBS containing 3% BSA for 15 min and then in a humid atmosphere with goat antirabbit {gamma}-globulins labeled with fluorescein for 1 h (1:100 dilution in a final volume of 0.04 ml/coverslip). For nuclei staining, cells were washed and stained with 0.15 µM propidium iodide (0.04 ml/coverslip for 3 min), washed in PBS, mounted under 13-mm coverslips with immunofluorescence medium, viewed through a x40 objective using a Diaphot fluorescence microscope (Nikon, Melville, NY), and counted. An identical procedure was used for immunodetection of GPDH in mouse Ob1771 cultured adipocytes.

Miscellaneous
Antimouse GPDH Igs were raised in rabbits and purified as previously described (28). GPDH activity (expressed in milliunits per mg) and protein concentration were determined as previously described (27).

Materials
FBS was a product of Life Technologies, Inc. (Cergy-Pontoise, France). Prostacyclin and (carba)prostacyclin were products of Cayman Chemicals (Ann Arbor, MI). All other products as well as conjugated goat antirabbit Igs were purchased from Sigma-Aldrich Corp. (Saint Quentin Fallavier, France).

Statistical analysis
Statistical comparisons were performed on absolute values by ANOVA with use of ANOVA from the StatView Student’s software package (Abacus Concepts, Inc., Berkeley, CA).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Specificity of GPDH antibodies and GPDH immunostaining during adipocyte differentiation
Preliminary investigations had shown that upon adipose differentiation of stromal-vascular cells in ITT medium (27), immunostaining of GPDH was increased (see Fig. 1DGo compared with Fig. 1EGo). However, a 2-day culture period was routinely selected, as it is the minimal time required to observe differences between cells after their isolation from unstimulated and stimulated fat pad explants. To characterize the specificity of GPDH antibodies, immunochemical staining of GPDH was performed in stromal-vascular cells isolated from epididymal fat pads of wild-type mice, GPDH-null mice, and transgenic mice overexpressing GPDH (Fig. 1Go, A–C). As shown in Fig. 1AGo, GPDH was detected in stromal-vascular cells from wild-type mice, showing fluorescence concentrated in the vicinity of nuclei. No labeling was observed in stromal-vascular cells isolated from GPDH-null mouse mutants (Fig. 1BGo) even after 1 week in culture (not shown), whereas labeling became intense and spread within the cytosol of stromal-vascular cells from GPDH-overexpressing mice (Fig. 1CGo). To ascertain the specificity of GPDH antibodies, immunostaining of mouse Ob1771 cells was also carried out as a function of adipocyte differentiation. Confluent cells, which express various early markers, but express GPDH only at very low levels (14, 15, 16) and have not yet accumulated triacylglycerol droplets, exhibited a weak immunostaining of GPDH (Fig. 1DGo). In contrast, differentiated Ob1771 cells exhibited a strong fluorescence in lipid droplet-containing cells (Fig. 1EGo). These observations were in agreement with GPDH activities, which were respectively 9 mU/mg in confluent cells and 591 mU/mg in 12-day postconfluent, differentiated cells. As expected, no fluorescence labeling was detected in differentiated Ob1771 cells using the nonimmune rabbit {gamma}-globulin fraction (Fig. 1FGo). Antimouse GPDH Igs were clearly able to cross-react with the rat enzyme, as revealed by immunochemical staining of GPDH in stromal-vascular cells isolated from rat epididymal fat pads that were cultured for 2 days and showed a GPDH activity of 146 mU/mg (Fig. 1GGo), whereas no labeling was observed in the same cells using the nonimmune {gamma}-globulin fraction (Fig. 1HGo).



View larger version (88K):
[in this window]
[in a new window]
  		Figure 1. Specificity of GPDH antibodies and immunochemical staining of GPDH during adipocyte differentiation. The first horizontal row of micrographs represents immunochemical staining of GPDH in cultured stromal-vascular cells isolated from epididymal fat pads of wild-type mice (A), GPDH-null mice (B), and GPDH-overexpressing mice (C). The second horizontal row of micrographs represents immunochemical staining of GPDH in mouse Ob1771 preadipocyte cells at confluence (day 0; D) and after differentiation (day 12; E and F). As indicated by arrows, fully differentiated cells were present in clusters, accumulated triacylglycerol droplets, and exhibited a strong immunofluorescence (E). No immunofluorescence was observed in differentiated cells using the nonimmune {gamma}-globulin fraction (F). The third horizontal row of micrographs represents staining of GPDH in cultured stromal-vascular cells from epididymal fat pad of male Wistar rats using the mouse GPDH antibodies (G) and the nonimmune {gamma}-globulin fraction (H). In each case, nuclei were stained in red with propidium iodide, whereas GPDH fluorescence appeared in green. Magnification, x400.

 
Appearance of GPDH-positive cells following (carba)prostacylin perfusion in vivo
Coculture experiments had shown that upon stimulation by AngII, prostacyclin secreted from adipocytes triggered from precursor cells the formation of new adipocytes, i.e. GPDH-positive, lipid-containing cells. To assess whether adipocyte differentiation of precursor cells could also take place in vivo, a single rat epididymal fat pad was perfused with (carba)prostacyclin for 5 h; perfusion of the contralateral pad with Ringer’s solution alone served as a control. Stromal-vascular cells were then isolated from both fat pads and cultured separately for 2 days in ITT medium (27). Subsequently, in each case, enumeration of cells expressing, or not, GPDH as well as enumeration of GPDH-positive cells containing, or not, lipid droplets were carried out. Compared with control untreated explants, it is clear from data in Table 1Go that perfusion of (carba)prostacyclin for 5 h led to a dramatic decrease in the proportion of undifferentiated stromal-vascular cells, i.e. GPDH- and lipid-negative cells, and this was associated with a significant increase in the proportion of differentiating cells, i.e. GPDH-positive, lipid-negative cells and, at least in Exp 1 and 2, in that of differentiated cells, i.e. GPDH-positive, lipid-containing cells. Although a strong adipogenic effect of (carba)prostacyclin could be observed in each case, it was difficult to obtain reproducible data on a quantitative basis, possibly due to differences 1) between animals and 2) in the localization of the microdialysis probe within individual pads. Therefore, we further tested the effects of AngII or (carba)prostacyclin in ex vivo experiments using adipose tissue fragments.


View this table:
[in this window]
[in a new window]
  		Table 1. Appearance of GPDH-positive cells after exposure of epididymal fat pad to (carba)prostacyclin (cPGI2) in vivo

 
Effect of angiotensin II and (carba)prostacyclin on adipose cell formation ex vivo
In the absence of effector, the results presented in Fig. 2Go show the occurrence of a spontaneous cyclooxygenasedependent formation of GPDH-positive cells during 20-h exposure, as this formation was nearly abolished in the presence of 100 µM aspirin. In these experiments, aspirin was selected as a cyclooxygenase inhibitor instead of indomethacin, because the latter behaves at micromolar concentrations as a PPAR{gamma} ligand and promotes adipocyte differentiation (29). Among hypotheses to explain this phenomenon, it is assumed that within control explants a release of prostacyclin and/or other unidentified adipogenic effectors is taking place, triggering, in turn, the differentiation of preadipocytes (29). Upon inclusion of AngII in the incubation medium, a statistically significant increase in the proportion of GPDH-positive cells was observed, which was also abolished by aspirin, strongly suggesting a cyclooxygenase-dependent phenomenon. From in vitro experiments, (carba)prostacyclin is known to induce the formation of GPDH-positive cells and the accumulation of triacylglycerol droplets (15, 16, 17, 30); this effect is not abolished by cyclooxygenase inhibitors (30). In agreement with these observations, the ex vivo experiments reported in Fig. 2Go show a statistical significant enhancement of the formation of GPDH-positive cells in (carba)prostacyclin-treated explants compared with untreated explants. As expected, aspirin inclusion to (carba)prostacyclin-treated explants did not alter this effect, although the limited number of experiments performed under these conditions did not allow us to draw definite conclusions.



View larger version (55K):
[in this window]
[in a new window]
  		Figure 2. Appearance of GPDH-positive cells containing, or not, lipid droplets upon exposure of rat WAT explants to AngII or (carba)prostacyclin. Rat WAT explants were for 20 h, either not exposed (control) or exposed to 1 µM AngII or 1 µM (carba)prostacyclin, in the absence or presence of 100 µM aspirin. Adipose tissue fragments were then processed for isolation and culture of stromal-vascular cells for 2 days as described in Materials and Methods. Enumeration of cells was carried out as described in Table 1Go. The reported values (mean ± SE) were obtained from four independent series of cells, except for the experiments performed in duplicate in the presence of (carba)prostacyclin plus aspirin. *, P < 0.05; **, P < 0.01 (vs. control). xx, P < 0.01 (vs. AngII).

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The role of AngII in the regulation of blood pressure is well known (31). Furthermore, AngII is known to act as a growth factor in a variety of tissues and cells (32, 33, 34, 35), but a trophic effect of AngII in adipose tissue development has not been previously reported. In this study AngII appears able to promote the formation of differentiating and differentiated cells from adipose precursor cells. This formation can be detected by the appearance of additional GPDH-positive cells when explants of white adipose tissue are stimulated by the hormone. Our observations are in agreement with those made in vivo, in which the emergence of GPDH in differentiating cells precedes a significant accumulation of triacylglycerol droplets (24). Our observations are also in agreement with the lipogenic effects of AngII in 3T3-L1 and human adipocytes, which is associated with increased activity and expression of GPDH and fatty acid synthase (14). It is likely that under the conditions used, the exposure time of explants is too short for cells expressing GPDH to synthesize triacylglycerol in sufficient amounts to be visualized under the microscope. In vivo, the adipogenic effect of (carba)prostacyclin is rapid and potent, consistent with our previous in vitro observations (15, 30) that prostacyclin released from adipocytes upon exposure to AngII is a paracrine link between adipocytes and precursor cells. Ex vivo experiments support also this hypothesis, as the effect of AngII is abolished by a cyclooxygenase inhibitor. Similar to that in vitro (30), when inhibition of cyclooxygenases by aspirin is bypassed by inclusion of (carba)prostacyclin, the emergence of GPDH-positive cells persists. Ex vivo, the adipogenic effect of AngII is observed at 0.1 µM and becomes statistically significant at 1 µM, which is 1 order of magnitude higher than the EC50 value determined in vitro (15) and 2 orders of magnitude higher than the Kd value of AngII receptors for its natural ligand (14), suggesting that low diffusion and/or metabolism of AngII may occur in adipose tissue fragments. The AngII receptor implicated in the above observations has not been characterized. To date, the AT2 receptor subtype is known to mediate the AngII effects in mouse adipose cells (14, 15), whereas the AT1 receptor subtype should be involved in rat adipocytes, as plasma membrane preparations show the presence of the AT1 subtype (13).

In summary, AngII appears to play an indirect role locally in adipocyte differentiation and to act via prostacyclin as a trophic factor of adipose tissue. In vivo, the use of wild-type and angiotensinogen-deficient mice may shed some light on this point.


   Acknowledgments
 
The authors thank Dr. Philippe Lenormand (UMR6543CNRS, Nice, France) for helpful advice, and Mrs. Geneviève Oillaux and Marie-Thérèse Ravier for expert secretarial and technical assistance, respectively.


   Footnotes
 
1 This work was supported by a grant from the Fondation pour la Recherche Médicale. Back

2 Present address: Nestlé Research Center, Molecular Nutrition, Vers chez les Blanc, CP44, CH-1000 Lausanne 26, Switzerland. Back

Received May 26, 2000.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Saye JA, Cassis LA, Sturgill TW, Lynch KR, Peach MJ 1989 Angiotensinogen gene expresssion in 3T3–L1 cells. Am J Physiol 256:C448–C451
  2. Saye J, Lynch KR, Peach MJ 1990 Changes in angiotensinogen messenger RNA in differentiating 3T3–F442A adipocytes. Hypertension 15:867–871[Abstract/Free Full Text]
  3. Aubert J, Darimont C, Safonova I, Ailhaud G, Négrel R 1997 Regulation by glucocorticoids of angiotensinogen gene expression and secretion in adipose cells. Biochem J 328:701–706
  4. Jones BH, Standridge MK, Taylor JW, Moustaid N 1997 Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control. Am J Physiol 273:R236–R242
  5. Karlsson C, Lindell K, Ottosson M, Sjöström L, Carlsson B, Carlsson LM 1998 Human adipose tissue expresses angiotensinogen and enzymes required for its conversion to angiotensin II. J Clin Endocrinol Metab 83:3925–3929[Abstract/Free Full Text]
  6. Grégoire FM, Smas CM, Sul HS 1998 Understanding adipocyte differentiation. Physiol Rev 78:783–809[Abstract/Free Full Text]
  7. Crandall DL, Herzlinger HE, Saunders BD, Kral JG 1994 Developmental aspects of the adipose tissue renin-angiotensin system: therapeutic implications. Drug Dev Res 32:117–125
  8. Harp JB, DiGirolamo M 1995 Components of the renin-angiotensin system in adipose tissue: changes with maturation and adipose mass enlargement. J Gerontol A Biol Sci Med Sci 50:B270–B276
  9. Schling P, Mallow H, Trindl A, Löffler G 1999 Evidence for a local renin angiotensin system in primary cultured human preadipocytes. Int J Obes 23:336–341
  10. Engeli S, Gorzelniak K, Kreutz R, Runkel N, Distler A, Sharma AM 1999 Co-expression of renin-angiotensin system genes in human adipose tissue. J Hypertens 17:555–560[CrossRef][Medline]
  11. Engeli S, Négrel R, Sharma AM 2000 Physiology and pathophysiology of the adipose tissue renin-angiotensin system. Hypertension 35:1270–1277[Abstract/Free Full Text]
  12. Saye JA, Ragsdale NV, Carey RM, Peach MJ 1993 Localization of angiotensin peptide-forming enzymes of 3T3–F442A adipocytes. Am J Physiol 264:C1570–C1576
  13. Crandall DL, Herzlinger HE, Saunders BD, Armellino DC, Kral JG 1994 Distribution of angiotensin II receptors in rat and human adipocytes. J Lipid Res 35:1378–1385[Abstract]
  14. Jones BH, Standridge MK, Moustaid N 1997 Angiotensin II increases lipogenesis in 3T3–L1 and human adipose cells. Endocrinology 138:1512–1519[Abstract/Free Full Text]
  15. Darimont C, Vassaux G, Ailhaud G, Négrel R 1994 Differentiation of preadipose cells: paracrine role of prostacyclin upon stimulation of adipose cells by angiotensin II. Endocrinology 135:2030–2036[Abstract]
  16. Vassaux G, Gaillard D, Ailhaud G, Négrel R 1992 Prostacyclin is a specific effector of adipose cell differentiation: its dual role as a cAMP- and Ca2+-elevating agent. J Biol Chem 267:11092–11097[Abstract/Free Full Text]
  17. Vassaux G, Gaillard D, Darimont C, Ailhaud G, Négrel R 1992 Differential response of preadipocytes and adipocytes to PGI2 and PGE2: physiological implications. Endocrinology 131:2393–2398[Abstract/Free Full Text]
  18. Börglum JD, Pedersen SB, Ailhaud G, Négrel R, Richelsen B 1999 Differential expression of prostaglandin receptor mRNAs during adipose cell differentiation. Prostaglandins Other Lipid Mediat 57:305–317[CrossRef][Medline]
  19. Aubert J, Saint-Marc P, Belmonte N, Dani C, Négrel R, Ailhaud G 2000 Prostacyclin IP receptor up-regulates the early expression of C/EBPß in preadipose cells. Mol Cell Endocrinol 160:149–156[CrossRef][Medline]
  20. Forman BM, Chen J, Evans RM 1997 Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors {alpha} and {delta}. Proc Natl Acad Sci USA 94:4312–4317[Abstract/Free Full Text]
  21. Aubert J, Ailhaud G, Négrel R 1996 Evidence for a novel regulatory pathway activated by (carba)prostacyclin in preadipose and adipose cells. FEBS Lett 397:117–121[CrossRef][Medline]
  22. Aubert J, Champigny O, Saint-Marc P, Négrel R, Collins S, Ricquier D, Ailhaud G 1997 Up-regulation of UCP-2 gene expression by PPAR agonists in preadipose and adipose cells. Biochem Biophys Res Commun 238:606–611[CrossRef][Medline]
  23. Darimont C, Vassaux G, Gaillard D, Ailhaud G, Négrel R 1994 In situ microdialysis of prostaglandins in adipose tissue: stimulation of prostacyclin release by angiotensin II. Int J Obes 18:783–788
  24. Cook JR, Kozak LP 1982 sn-Glycerol-3-phosphate dehydrogenase gene expression during mouse adipocyte development in vivo. Dev Biol 92:440–448[CrossRef][Medline]
  25. Prochazka M, Kozak UC, Kozak LP 1989 A glycerol-3-phosphate dehydrogenase null mutant in BALB/cHeA mice. J Biol Chem 264:4679–4683[Abstract/Free Full Text]
  26. Kozak LP, Kozak UC, Clarke GT 1991 Abnormal brown and white fat development in transgenic mice overexpressing glycerol-3-phosphate dehydrogenase. Genes Dev 6:2256–2264
  27. Deslex S, Négrel R, Vannier C, Etienne J, Ailhaud G 1987 Development of a chemically defined serum-free medium for complete differentiation of rat adipose precursor cells. Exp Cell Res 168:15–30[CrossRef][Medline]
  28. Fisher M, Gapp DA, Kozak LP 1981 Immunohistochemical localization of sn-glycerol-3-phosphate dehydrogenase in Bergmann glia and oligodendroglia in the mouse cerebellum. Dev Brain Res 1:341–354[CrossRef]
  29. Lehmannn JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA 1997 Peroxisome proliferator-activated receptors {alpha} and {gamma} are activated by indomethacin and other non-steroidal anti-inflammatory durgs. J Biol Chem 272:3406–3410[Abstract/Free Full Text]
  30. Négrel R, Gaillard D, Ailhaud G 1989 Prostacyclin as a potent effector of adipose cell differentiation. Biochem J 257:399–405[Medline]
  31. Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM, Corvol P 1992 Molecular basis of human hypertension: role of angiotensinogen. Cell 71:169–180[CrossRef][Medline]
  32. Sil P, Sen S 1997 Ang II and myocyte growth. Hypertension 30:209–216[Abstract/Free Full Text]
  33. Chung O, Stoll M, Unger T 1996 Physiologic and pharmacologic implications of AT1 versus AT2 receptors. Blood Press [Suppl] 2:47–52[Medline]
  34. Nakajima M, Hutchinson HG, Fujinaga M, Hayashida W, Morishita R, Zhaing L, Horiuchi M, Pratt RE, Dzau VJ 1995 The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer. Proc Natl Acad Sci USA 92:10663–10667[Abstract/Free Full Text]
  35. Meffert S, Stoll M, Steckelings UM, Bottari SP, Unger T 1996 The angiotensin II AT2 receptor inhibits proliferation and promotes differentiation in PC12W cells. Mol Cell Endocrinol 122:59–67[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. D. Fowler, N. D. Johnson, T. A. Haroldson, J. A. Brintnall, J. E. Herrera, S. A. Katz, and D. A. Bernlohr
Regulated renin release from 3T3-L1 adipocytes
Am J Physiol Endocrinol Metab, June 1, 2009; 296(6): E1383 - E1391.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. D. Fowler, S. B. Krueth, D. A. Bernlohr, and S. A. Katz
Renin dynamics in adipose tissue: adipose tissue control of local renin concentrations
Am J Physiol Endocrinol Metab, February 1, 2009; 296(2): E343 - E350.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. P. Jayasooriya, M. L. Mathai, L. L. Walker, D. P. Begg, D. A. Denton, D. Cameron-Smith, G. F. Egan, M. J. McKinley, P. D. Rodger, A. J. Sinclair, et al.
Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance
PNAS, May 6, 2008; 105(18): 6531 - 6536.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
B Galvez-Prieto, J Bolbrinker, P Stucchi, A I de las Heras, B Merino, S Arribas, M Ruiz-Gayo, M Huber, M Wehland, R Kreutz, et al.
Comparative expression analysis of the renin-angiotensin system components between white and brown perivascular adipose tissue
J. Endocrinol., April 1, 2008; 197(1): 55 - 64.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
V. Achard, S. Boullu-Ciocca, R. Desbriere, G. Nguyen, and M. Grino
Renin receptor expression in human adipose tissue
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R274 - R282.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
K. Matsushita, Y. Wu, Y. Okamoto, R. E. Pratt, and V. J. Dzau
Local Renin Angiotensin Expression Regulates Human Mesenchymal Stem Cell Differentiation to Adipocytes
Hypertension, December 1, 2006; 48(6): 1095 - 1102.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
K. Tsuchiya, T. Yoshimoto, Y. Hirono, T. Tateno, T. Sugiyama, and Y. Hirata
Angiotensin II induces monocyte chemoattractant protein-1 expression via a nuclear factor-{kappa}B-dependent pathway in rat preadipocytes
Am J Physiol Endocrinol Metab, October 1, 2006; 291(4): E771 - E778.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
M. Maslowska, H. Legakis, F. Assadi, and K. Cianflone
Targeting the signaling pathway of acylation stimulating protein
J. Lipid Res., March 1, 2006; 47(3): 643 - 652.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
A. Baudry, Z.-Z. Yang, and B. A. Hemmings
PKB{alpha} is required for adipose differentiation of mouse embryonic fibroblasts
J. Cell Sci., March 1, 2006; 119(5): 889 - 897.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C.-C. Juan, Y. Chien, L.-Y. Wu, W.-M. Yang, C.-L. Chang, Y.-H. Lai, P.-H. Ho, C. F. Kwok, and L.-T. Ho
Angiotensin II Enhances Insulin Sensitivity in Vitro and in Vivo
Endocrinology, May 1, 2005; 146(5): 2246 - 2254.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
L. Yvan-Charvet, P. Even, M. Bloch-Faure, M. Guerre-Millo, N. Moustaid-Moussa, P. Ferre, and A. Quignard-Boulange
Deletion of the Angiotensin Type 2 Receptor (AT2R) Reduces Adipose Cell Size and Protects From Diet-Induced Obesity and Insulin Resistance
Diabetes, April 1, 2005; 54(4): 991 - 999.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
V. Serazin, M.-N. Dieudonne, M. Morot, P. de Mazancourt, and Y. Giudicelli
cAMP-positive regulation of angiotensinogen gene expression and protein secretion in rat adipose tissue
Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E434 - E438.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
A. M. Sharma, J. Janke, K. Gorzelniak, S. Engeli, and F. C. Luft
Angiotensin Blockade Prevents Type 2 Diabetes by Formation of Fat Cells
Hypertension, November 1, 2002; 40(5): 609 - 611.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. Janke, S. Engeli, K. Gorzelniak, F. C. Luft, and A. M. Sharma
Mature Adipocytes Inhibit In Vitro Differentiation of Human Preadipocytes via Angiotensin Type 1 Receptors
Diabetes, June 1, 2002; 51(6): 1699 - 1707.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
S. Kim, J. Whelan, K. Claycombe, D. B. Reath, and N. Moustaid-Moussa
Angiotensin II Increases Leptin Secretion by 3T3-L1 and Human Adipocytes via a Prostaglandin-Independent Mechanism
J. Nutr., June 1, 2002; 132(6): 1135 - 1140.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
F. Massiera, J. Seydoux, A. Geloen, A. Quignard-Boulange, S. Turban, P. Saint-Marc, A. Fukamizu, R. Negrel, G. Ailhaud, and M. Teboul
Angiotensinogen-Deficient Mice Exhibit Impairment of Diet-Induced Weight Gain with Alteration in Adipose Tissue Development and Increased Locomotor Activity
Endocrinology, December 1, 2001; 142(12): 5220 - 5225.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Saint-Marc, P.
Right arrow Articles by Negrel, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saint-Marc, P.
Right arrow Articles by Negrel, R.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals