Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern?

MESH: Signal Transduction Male Cytoplasmic and Nuclear Receptors, Cytoplasmic and Nuclear Inbred C57BL MESH: Mice, Knockout Biochemistry Mice MESH: Pregnancy Pregnancy Receptors MESH: Fatty Acids, Omega-6 MESH: Receptors Cyclic AMP MESH: Receptors, Epoprostenol MESH: Animals [SDV.BDD]Life Sciences [q-bio]/Development Biology MESH: Cyclic AMP Omega-6 Mice, Knockout 2. Zero hunger 0303 health sciences Arachidonic Acid Fatty Acids Biologie du développement pregnancy-lactation Cell Differentiation MESH: Transcription Factors Development Biology MESH: Fatty Acids 3. Good health Adipose Tissue MESH: Dietary Fats prostacyclin receptor-deficient mice Female childhood obesity MESH: Adipose Tissue Signal Transduction MESH: Cell Differentiation Knockout 610 QD415-436 MESH: Receptors, Cytoplasmic and Nuclear MESH: Epoprostenol Receptors, Epoprostenol adipogenesis 03 medical and health sciences MESH: Mice, Inbred C57BL Fatty Acids, Omega-6 Animals Humans MESH: Mice Adipose Tissue;Animals;Arachidonic Acid;Body Weight;Cell Differentiation;Cyclic AMP;Dietary Fats;Epoprostenol;Fatty Acids;Omega-6;Female;Fibroblasts;Humans;Male;Mice;Inbred C57BL;Knockout;Pregnancy;Receptors;Cytoplasmic and Nuclear;Signal Transduction;Transcription Factors MESH: Humans Body Weight Fibroblasts Dietary Fats Epoprostenol MESH: Male MESH: Arachidonic Acid MESH: Body Weight Mice, Inbred C57BL MESH: Fibroblasts MESH: Female Transcription Factors
DOI: 10.1194/jlr.m200346-jlr200 Publication Date: 2003-02-07T21:24:36Z
ABSTRACT
High fat intake is associated with mass gain through fatty acid activation of peroxisome proliferator-activated receptors δ and γ, which promote adipogenesis. We show herein that, compared to a combination specific agonists both or saturated, monounsaturated, ω-3 polyunsaturated acids, arachidonic (C20:4, ω-6) promoted substantially the differentiation clonal preadipocytes. This effect was blocked by cyclooxygenase inhibitors mimicked carbacyclin, suggesting role for prostacyclin receptor cyclic AMP-dependent pathways that regulate expression CCAAT enhancer binding proteins β implicated in During pregnancy-lactation period, mother mice were fed either high-fat diet rich linoleic acid, precursor (LO diet), same isocaloric enriched α-linolenic (LO/LL diet). Body weight from weaning onwards, mass, epididymal pad weight, adipocyte size at 8 weeks age higher LO than LO/LL diet. In contrast, receptor-deficient similar this respect, indicating signaling contributes adipose tissue development.These results raise issue high content i) ingested lipids during pregnancy lactation, ii) formula milk infant foods relation epidemic childhood obesity. development. These Obesity metabolic disorders such as dyslipidemia, diabetes, hypertension, excess severe obesities typically due an increase number. The formation adipocytes critical event, mature do not divide vivo undergo significant turnover under physiological conditions. capacity proliferation cells their into highest early decrease thereafter humans rodents. A limited number hormones can affect possibly its distribution (1Ailhaud G. Hauner H. Development white tissue.in: Bray Bouchard C. James P.T. Handbook Obesity. M. Dekker Inc., New York, NY1997: 359-378Google Scholar). dietary now recognized be animals all ages (2Troiano R.P. Briefel R.R. Carrol D.M. Bialostosky K. 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Moriwaki Perilla visceral down-regulating differentiation.J. 127: 1752-1757Google mechanisms underlying differential adipogenic ω-6 versus suggest differences and/or metabolites promoting adipocytes. vitro, preadipocyte stage, member (PPAR) family, i.e., PPARδ, two members CCAAT-enhancer protein C/EBPβ C/EBPδ, act concomitantly upregulate subsequent PPARγ leading adipogenesis (11Barak Nelson M.C. Ong E.S. Jones Y.Z. Ruiz-Lozano Chien K.R. Kader Evans R.M. required placental, cardiac, development.Mol. Cell. 4: 585-595Google 12Kubota Terauchi Miki Tamemoto Yamauchi Komeda Satoh Nakano Ishii Sugiyama Eto Tsubamoto Okuno Murakami Sekihara Hasegawa Naito Toyoshima Tanaka Shiota Kitamura Fujita Ezaki O. Aizawa Nagai Tobe Kimura Kadowaki mediates diet-induced insulin resistance.Mol. 597-609Google 13Rosen E.D. Sarraf Troy A.E. Bradwin Moore Milstone D.S. Spiegelman B.M. Mortensen vitro.Cell. 611-617Google 14Ren Collingwood T.N. Rebar E.J. Wolffe A.P. Camp H.S. knockdown engineered transcription factors: exogenous PPARγ2 PPARγ1 reactivates adipogenesis.Genes Dev. 2002; 16: 27-32Google 15Rosen Hsu Wang X. Sakai Freeman M.W. Gonzalez F.J. C/EBPα induces PPARγ: unified pathway.Genes 22-26Google Natural long-chain preadipocytes hormones, participate transcriptional regulators various lipid-related genes, (16Amri E. Ailhaud Grimaldi Fatty signal transducing molecules: involvement preadipose cells.J. 1994; 35: 930-937Google implicate PPARs bind (17Xu H.E. Lambert M.H. Montana V.G. Parks D.J. Blanchard S.G. P.J. Sternbach D.D. Lehmann J.M. Wisely G.B. Willson T.M. Kliewer S.A. Milburn M.V. Molecular recognition receptors.Mol. 3: 397-403Google Among ω-6, ARA), prostaglandin I2 (prostacyclin), synthesized released preadipocytes, has been identified one main components serum. Arachidonic rapid cAMP production. Both are impaired aspirin indomethacin (18Gaillard Négrel Lagarde Requirement cells.Biochem. 1989; 257: 389-397Google Consistent autocrine-paracrine mechanism via prostacyclin, antibodies directed against prostanoid added externally half (19Catalioto Gaillard Maclouf Autocrine control cell PGF2α.Biochim. Biophys. Acta. 1991; 1091: 364-369Google Also consistent acting ligand surface, it shown stable analog carbacyclin mimic (20Négrel Prostacyclin potent effector differentiation.Biochem. 399-405Google Scholar) mouse primary human (21Vassaux differentiation: dual cAMP- Ca2+-elevating agent.J. Chem. 1992; 267: 11092-11097Google surface (IP-R) activates kinase (PKA) pathway upregulates C/EBPδ (22Belmonte Phillips B.W. Massiéra F. Villageois Wdziekonski Saint-Marc Nichols Aubert Saeki Yuo Narumiya Dani Activation extracellular signal-regulated kinases CREB/ATF-1 mediate preadipocytes.Mol. Endocrinol. 2001; 15: 2037-2049Google Circumstantial favors possibility binds like PPARδ (23Forman Chen Hypolipidemic drugs, eicosanoids ligands α δ.Proc. Natl. Acad. Sci. USA. 94: 4312-4317Google recently supported studies stromal surrounding implanting blastocysts (24Lim Gupta R.A. Ma W. Paria B.C. Moller Morrow J.D. DuBois R.N. Trzaskos Dey S.K. Cyclo-oxygenase-2-derived embryo implantation PPARδ.Genes 13: 1561-1574Google vivo, invalidation genes impairs severely does abolish (25Tanaka Yoshida Kishimoto Akira Defective lacking gene.EMBO 7432-7443Google whereas leads controversial disproportionate (26Peters Lee S.S.T. Li Ward Gavrilova Everett Reitman M.L. Hudson L.D. Growth, adipose, brain skin alterations resulting targeted disruption (δ).Mol. 20: 5119-5128Google 27Barak Liao He F.S. Olefsky Boland Effects delta placentation, colorectal cancer.Proc. 99: 303-308Google suggests signaling, arising metabolism, play more important up-regulating expression. order estimate importance regulatory pathways, we have taken advantage recent availability PPAR generation receptor-null (ip-r−/−) (28Murata Ushikubi Matsuoka Hirata Yamasaki Sugimoto Ichikawa Aze Oh-ishi Altered pain perception inflammatory response receptor.Nature. 388: 678-682Google Our wild-type ip-r−/− series equipotent vitro favor process. infants, given enrichment consumption time where dynamic phase ip-r-null established targeting backcrossed C57/BL6J least 10 generations then males females bred generate further generations. maintained light/dark cycle light 6 AM PM 25°C. female designated mothers standard consisted (by energy) 7% fat, 66% carbohydrates, 27% proteins, containing 15% corn diet) mixture 10% 5% perilla diets 40% 35% 25% supplemented 0.04% vitamin C 0.02% E (UAR, Carbon Blanc, France). Corn contained, expressed g/100 g total 13% 59% polyunsaturated, 1% acids. contained 10.9% 22.9% 44.3% 21.9% At age, since male throughout mating, pregnancy, lactation 18 weaned onto had consumed thereafter. Food composition, cellularity measurements performed described previously (29Massiéra Seydoux Geloen Quignard-Boulangé Turban Fukamizu Teboul Angiotensinogen-deficient exhibit impairment alteration increased locomotor activity.Endocrinology. 142: 5220-5225Google All experimental animal protocols accordance recommendations French Accreditation Laboratory Animal Care. Embryos C57 BL/6J 14.5 day postcoitus used prepare fibroblasts removing head, heart, legs. Mouse differentiated Stock cultures Ob1771 Dulbecco’s modified Eagle’s medium (Gibco, Cergy-Pontoise, France) biotin, pantothenate, antibiotics, 8% (v/v) fetal bovine serum Experiments confluent serum-free prostaglandins (Cayman Chemicals, Montluçon, France), GW2433, BRL49653 dissolved ethanol 1:100 dilution culture media. Ethanol concentration, did exceed 1%, no conversion AMP Oil-Red O staining Glycerol-3-phosphate dehydrogenase assays carried out duplicate 7 confluence Intracellular determined commercial kit radioimmunoassay, according manufacturer’s instructions (Amersham). Before assays, extracted 1.2 ml ice-cold ethanol-5 mM-EDTA (2:1, v/v). After scraping monolayer centrifugation, 1 supernatant dried Speed-Vac evaporator. Duplicate samples solubilized before 150 μl 50 mM Tris-HCl buffer, pH 7.5, 4 EDTA assayed duplicate. Statistical comparisons absolute values Fisher's PLSD using STATVIEW software package. experiments exposed absence (Fig. 1A)or presence effectors. Differentiation enhanced naturally abundant ARA 1B) ARA, only present trace amounts sources 1C). when included inhibitor 1D). Another series, behaved similarly 1E). agreement our previous observations IP-R, highly 1F), exhibiting greater agonist 1G), GW2433 BRL49663, (30Lehmann Smith-Oliver T.A. Wilkison W.O. An antidiabetic thiazolidinedione affinity γ (PPARγ).J. 1995; 270: 12953-12956Google 1H). delineate step active process, first studied maximally effective concentrations glycerol-3-phosphate activity, indicator. sequential addition based upon several considerations. Early markers PPARγ−/− embryonic stem committed lineage, lipoprotein lipase lipid (ALBP aP2) (31Vernochet Iehlé Belmonte Amri E.Z. O’Donnell PPARγ-dependent PPARγ-independent cells.FEBS Lett. 510: 94-98Google Scholar); near maximal levels cells, PPARγ, later (32Amri Bonino Abumrad P.A. Cloning Homology receptors.J. 2367-2371Google iii) activators-ligands (33Bastié Luquet Holst Jehl-Pietri Expression promotes induction 3T3C2 fibroblasts.J. 274: 21920-21925Google 34Hansen J.B. Zhang Rasmussen T.H. Petersen Flindt E.N. Kristiansen Peroxisome (PPARδ)-mediated dependent signaling.J. 276: 3175-3182Google these observations, 0 3, followed removal 3 7, proved optimal. Adipogenesis observed 7. discontinuous continuous exposure less efficient (Table 1, A). Of note, potency 3-fold reduced inhibition potencies similar. Interestingly, Altogether, substantial takes place step(s) fact observe synthesis IP-R differentiating, PPARγ-expressing Scholar).TABLE 1Comparative stimulation acidsAddition Day 3Addition 7GPDH Activity (Fold Increase)Part ANoneNone1.0a30 ± mU/mg protein.Noneγ agonist2.4 0.6δ agonistNone3.6 0.8bP < 0.05 untreated cells.δ agonistγ agonist5.7 1.6cP 0.01 agonistδ agonist2.1 1.0γ agonist5.2 1.0cP + agonistsδ agonists6.6 2.1cP cells.5 μM ARAγ agonist9.3 cells.10 agonist17.5 6.2cP 100 aspirinγ agonist4.4 1.4bP agonist2.6 0.7bP agonist5.5 1.2cP agonist1.5 0.3δ agonist5 ω−6 ARA4.9 2.3bP ω−3 ARA5.8 cells.Carbacyclinγ agonist17.3 3.0cP cells.Part B5 Palmitic acidγ agonist1.9 0.610 agonist2.3 0.5bP Palmitoleic agonist3.0 0.6bP agonist3.5 Oleic agonist2.7 agonist2.2 0.4bP EPAd10 cytotoxic basis.γ 0.9bP DHAγ agonist4.1 1.210 cells.ARA, acid; agonist, (1 μM); (0.5 (0.2 μM). Values mean SEM 3–10 independent cells.a 30 protein.b P cells.c cells.d basis. Open table new tab cells. insights BMY45778, unable activate (35Aubert IP up-regulates cells.Mol. 160: 149-156Google agonist. 2-fold while BMY45778 enhance above alone (data shown). As appears remarkable likely role, PKA turn up-regulation (36Wu Z. Bucher Farmer S.R. Induction gamma 3T3 mediated C/EBPbeta, C/EBPdelta glucocorticoids.Mol. 4128-4136Google second PPARδ. stimulate events next examined subsequently B). (palmitate) monounsaturated (palmitoleate oleate) poorly ARA. Furthermore, adipogenic. cannot ascribed latter unique natural extensive differentiation, production very short 2). 15-fold 5 min abolished indo
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