AdipoQ Is a Novel Adipose-specific Gene Dysregulated in Obesity

Abstract

Adipose differentiation is accompanied by changes in cellular morphology, a dramatic accumulation of intracellular lipid and activation of a specific program of gene expression. Using an mRNA differential display technique, we have isolated a novel adipose cDNA, termed adipoQ. The adipoQ cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a collagenous region (Gly-X-Y repeats), and a globular domain. The globular domain of adipoQ shares significant homology with subunits of complement factor C1q, collagen α1(X), and the brain-specific factor cerebellin. The expression of adipoQ is highly specific to adipose tissue in both mouse and rat. Expression of adipoQ is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain adipoQ mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for adipoQ. Furthermore, the expression of adipoQ mRNA is significantly reduced in the adipose tissues from obese mice and humans. Whereas the biological function of this polypeptide is presently unknown, the tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue. Adipose differentiation is accompanied by changes in cellular morphology, a dramatic accumulation of intracellular lipid and activation of a specific program of gene expression. Using an mRNA differential display technique, we have isolated a novel adipose cDNA, termed adipoQ. The adipoQ cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a collagenous region (Gly-X-Y repeats), and a globular domain. The globular domain of adipoQ shares significant homology with subunits of complement factor C1q, collagen α1(X), and the brain-specific factor cerebellin. The expression of adipoQ is highly specific to adipose tissue in both mouse and rat. Expression of adipoQ is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain adipoQ mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for adipoQ. Furthermore, the expression of adipoQ mRNA is significantly reduced in the adipose tissues from obese mice and humans. Whereas the biological function of this polypeptide is presently unknown, the tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue. INTRODUCTIONAdipose tissue is highly specialized to play important roles in energy storage, fatty acid metabolism, and glucose homeostasis(1.Cornelius P. MacDougald O.A. Lane M.D. Annu. Rev. Nutr. 1994; 14: 99-129Crossref PubMed Scopus (572) Google Scholar, 2.Spiegelman B.M. Choy L. Hotamisligil G.S. Graves R.A. Tontonoz P. J. Biol. Chem. 1993; 268: 6823-6826Abstract Full Text PDF PubMed Google Scholar). Adipocytes synthesize and store triglyceride in periods of nutritional abundance and mobilize the lipids in response to fasting(2.Spiegelman B.M. Choy L. Hotamisligil G.S. Graves R.A. Tontonoz P. J. Biol. Chem. 1993; 268: 6823-6826Abstract Full Text PDF PubMed Google Scholar, 3.Spiegelman B.M. Hotamisligil G.S. Cell. 1993; 73: 625-627Abstract Full Text PDF PubMed Scopus (199) Google Scholar). Fat tissue is also involved in regulating blood glucose levels through the expression of the insulin responsive glucose transporter, Glu4(4.Kaestner K.H. Christy R.J. McLenithan J.C. Braiterman L.T. Cornelius P. Pekala P.H. Lane M.D. Proc. Natl. Acad. Sci. U. S. A. 1989; 86: 3150-3154Crossref PubMed Scopus (248) Google Scholar, 5.Kaestner K.H. Christy R.J. Lane M.D. Proc. Natl. Acad. Sci. U. S. A. 1990; 87: 251-255Crossref PubMed Scopus (226) Google Scholar). Fat and muscle, in fact, constitute the two major sites for insulin-regulated glucose uptake.At a molecular level, many genes involved in lipid metabolism and glucose homeostasis are prominently expressed in fat(1.Cornelius P. MacDougald O.A. Lane M.D. Annu. Rev. Nutr. 1994; 14: 99-129Crossref PubMed Scopus (572) Google Scholar). These include fatty acid synthase(6.Moustaid N. Sul H.S. J. Biol. Chem. 1991; 266: 18550-18554Abstract Full Text PDF PubMed Google Scholar), the fatty acid binding protein aP2(7.Spiegelman B.M. Frank M. Green H. J. Biol. Chem. 1983; 258: 10083-10089Abstract Full Text PDF PubMed Google Scholar, 8.Hunt C.R. Ro J.H.-S. Dobson D.E. Min H.Y. Spiegelman B.M. Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 3786-3790Crossref PubMed Scopus (266) Google Scholar), lipoprotein lipase(9.Cornelius P. Enerback S. Bjursell G. Olivecrona T. Pekala P.H. Biochem. J. 1988; 249: 765-769Crossref PubMed Scopus (99) Google Scholar), phosphoenolpyruvate carboxykinase(10.Beale E.G. Tishler E.J. Biochem. Biophys. Res. Commun. 1992; 189: 925-930Crossref PubMed Scopus (13) Google Scholar), malic enzyme(11.Wise L.S. Sul H.S. Rubin C.S. J. Biol. Chem. 1984; 259: 4827-4832Abstract Full Text PDF PubMed Google Scholar), glyceraldehyde-3-phosphate dehydrogenase(12.Alexander M. Curtis G. Avruch J. Goodman H.M. J. Biol. Chem. 1985; 260: 11978-11985Abstract Full Text PDF PubMed Google Scholar), and Glut4 (4.Kaestner K.H. Christy R.J. McLenithan J.C. Braiterman L.T. Cornelius P. Pekala P.H. Lane M.D. Proc. Natl. Acad. Sci. U. S. A. 1989; 86: 3150-3154Crossref PubMed Scopus (248) Google Scholar). Receptors for lipogenic or lipolytic hormones such as insulin(13.Reed B.C. Lane M.D. Proc. Natl. Acad. Sci. U. S. A. 1980; 77: 285-289Crossref PubMed Scopus (161) Google Scholar, 14.Rubin C.S. Hirsch A. Fung C. Rosen O.M. J. Biol. Chem. 1978; 253: 7570-7578Abstract Full Text PDF PubMed Google Scholar), insulin-like growth factor 1(15.Campfield L.A. Smith F.J. Guisez Y. Devos R. Burn P. Science. 1995; 269: 546-549Crossref PubMed Scopus (3060) Google Scholar), and adrenergic compounds (16.Feve B. Emorine L.J. Briend-Sutren M.M. Lasnier F. Strosberg A.D. Pairault J. J. Biol. Chem. 1990; 265: 16343-16349Abstract Full Text PDF PubMed Google Scholar, 17.Guest S.J. Hadcock J.R. Watkins D.C. Malbon C.C. J. Biol. Chem. 1990; 265: 5370-5375Abstract Full Text PDF PubMed Google Scholar) are also expressed in adipocytes. In addition to these genes that clearly participate in the metabolic functions of adipose tissue, a group of genes that function in extracellular signaling have also been identified in fat. A prototype of these molecules is insulin-like growth factor 1, which is expressed in many tissues during development and plays an important role in cell proliferation(18.Froesch E.R. Schmid C. Schwander J. Zapf J. Annu. Rev. Physiol. 1985; 47: 443-467Crossref PubMed Google Scholar). In adipocytes, however, insulin-like growth factor 1 is found to stimulate cell differentiation(19.Smith P. Wise L.S. Berkowitz R. Wan C. Rubin C.S. J. Biol. Chem. 1988; 263: 9402-9408Abstract Full Text PDF PubMed Google Scholar). More interestingly, insulin-like growth factor 1 is synthesized by preadipocytes in response to growth hormone stimulation(20.Doglio A. Dani C. Fredrikson G. Grimaldi P. Ailhaud G. EMBO J. 1987; 6: 4011-4016Crossref PubMed Scopus (92) Google Scholar), thus potentially functioning in an autocrine or paracrine fashion to promote adipogenesis during development. Another signaling molecule from adipose tissue is TNF-α. 1The abbreviations used are: TNF-αtumor necrosis factor αDMEMDulbecco's modified Eagle's mediumPCRpolymerase chain reaction. TNF-α is secreted from fat, especially in obesity, and acts in an autocrine or paracrine manner to interfere with insulin action in fat and muscle(21.Hotamisligil G. Shargill N.S. Spiegelman B.M. Science. 1993; 259: 87-91Crossref PubMed Scopus (6031) Google Scholar, 22.Hotamisligil G.S. Arner P. Caro J.F. Atkinson R.L. Spiegelman B.M. J. Clin. Invest. 1995; 95: 2409-2415Crossref PubMed Scopus (2941) Google Scholar). The recent cloning and of the gene that adipose tissue signaling molecules that function in an Y. R. M. M. L. 1994; PubMed Scopus Google Scholar). The gene is secreted from fat the and acts to a putative in the region of the L.A. Smith F.J. Guisez Y. Devos R. Burn P. Science. 1995; 269: 546-549Crossref PubMed Scopus (3060) Google Scholar, Y. R. M. M. L. 1994; PubMed Scopus Google Scholar, M. R.L. Science. 1995; 269: PubMed Scopus Google Scholar). molecules secreted from adipose tissue are of functions in fat and thus a of adipose tissue this we have used mRNA differential display to a novel adipose gene termed adipoQ. suggests that adipoQ is a secreted protein that shares significant homology to subunits of complement factor and a collagenous at the and a globular domain at the The expression of this novel gene is highly during the adipose differentiation and is expressed in adipose tissue in a significant in adipoQ mRNA observed in fat tissues from obese mice and humans. a potentially molecular to the of adipose tissue in and and from and from and from and from from and cells and 3T3-F442A and 3T3-L1 preadipocytes cultured as B.M. Frank M. Green H. J. Biol. Chem. 1983; 258: 10083-10089Abstract Full Text PDF PubMed Google Scholar, H. Cell. Full Text PDF Scopus Google Scholar). of differentiation as P. Graves R.A. Spiegelman B.M. 1994; PubMed Scopus Google Scholar). differentiation by of insulin at at for 3T3-F442A cells and and insulin for 3T3-L1 3T3-L1 cells with for and by and Using this of the cells in both cell an the of and differentiation the differential display as P. Science. 1992; PubMed Scopus Google Scholar, P. L. Res. 1993; PubMed Scopus Google Scholar). cellular isolated from 3T3-F442A preadipocytes, and 3T3-F442A the R.J. PubMed Scopus Google Scholar). of with of of used in a of the P. L. F. Res. 1994; PubMed Scopus Google Scholar) and of in as by the of the cDNA used for reaction. the and of in The sequence of the that is The 1 of of and and of for of at for at for 1 and at for of the a sequence and by the to from the and the from the by the in 1 for The by the and the cloning cDNA and cDNA and as T. J. A Scholar). cDNA by as P. Graves R.A. Spiegelman B.M. 1994; PubMed Scopus Google Scholar). the program at the in and homology and the program from the sequence of and a in from to the used to the protein and from of sequence of adipoQ expression and The the The with as T. J. A Scholar). cells with and with and cells with as T. J. A Scholar). used to the and isolated from both 3T3-F442A and 3T3-L1 cell as as from and tissues as R.J. PubMed Scopus Google Scholar, T. J. A Scholar). of in and at and in as T. J. A Scholar). and the and as by the cDNA to specific of at with the B. Biochem. 1984; PubMed Scopus Google of Fat and Fat of fat as F. G. N. C. Biol. Cell. 1990; PubMed Scopus Google Scholar). fat and the with and The fat by and with for at The cell through a and at for The mature and The and and the stromal-vascular fraction with and isolated as R.J. PubMed Scopus Google of novel genes that are expressed during adipose we an mRNA differential display P. Science. 1992; PubMed Scopus Google Scholar, P. L. Proc. Natl. Acad. Sci. U. S. A. 1994; PubMed Scopus Google Scholar). from cells a cell to adipocytes, and a cell 3T3-F442A cells and H. Cell. Full Text PDF Scopus Google Scholar, H. Cell. Full Text PDF PubMed Scopus Google Scholar). The used to synthesize the cDNA, which used for differential display A of in expressed in mature not and we such A cDNA for by and significant sequence homology with genes in from this putative in this this cDNA a mRNA expressed in fat cells These that this cDNA a mRNA that A of by a cDNA with the cDNA a in the cDNA and amino acid of homology to of C1q, collagen α1(X), and cerebellin. are from the of the The amino acid sequence is from the The region the domain. are The for adipoQ in is homology of adipoQ with and The region amino acids in in collagenous region of and are by an and the that are in adipoQ. of the globular region collagen α1(X), and cerebellin. or in are by The two that are are adipoQ and collagen α1(X), and and in and of adipoQ in used for of cDNA to the with of and of and is by at the of the of from and cell of cells Lane 1 and 1 of in and and of of from and and of of cell from and The and with from of the putative protein sequence identified a from amino acid to a signal A region of collagenous from amino acids to with with genes in identified of homology to the subunits and of complement factor F. M. J. 1991; Google Scholar, F. M. J. Biochem. 1992; PubMed Scopus Google Scholar), a tissue-specific collagen R. M. S. M. B. Biochem. J. 1993; PubMed Scopus Google Scholar), and a brain-specific protein Y. J. R. Proc. Natl. Acad. Sci. U. S. A. 1991; PubMed Scopus Google Scholar). The with the is in the globular region with the homology in two of In adipoQ and and have a of amino acids The of is as with such for adipoQ and for the The of this protein to collagen and is found at the globular domain with and a acid α1(X), however, encodes a protein amino with a collagenous the is a polypeptide with amino acid and does not contain a collagenous Y. J. R. Proc. Natl. Acad. Sci. U. S. A. 1991; PubMed Scopus Google Scholar). of the this novel protein and of molecules in domain and we termed this novel protein is clearly a of a by a collagenous at the terminus, and a globular domain at the Annu. Rev. Biochem. 1995; PubMed Scopus Google Scholar). In addition to and F. M. J. 1991; Google Scholar, F. M. J. Biochem. 1992; PubMed Scopus Google Scholar) and collagen R. M. S. M. B. Biochem. J. 1993; PubMed Scopus Google Scholar), this protein and J. J. S. B. B. 1985; PubMed Scopus Google Scholar), binding L. J. Biol. Chem. 1986; Full Text PDF PubMed Google Scholar), and the and M. J. Annu. Rev. Biochem. 1994; PubMed Scopus Google Scholar, M. C. J. R. A. G. Cell. 1995; Full Text PDF PubMed Scopus Google Scholar). These or the collagenous The of a collagenous domain in adipoQ suggests that this protein is to by or with the region of adipoQ shares significant with the also a in in the globular region of and is to with H. M. M. J. 1990; PubMed Scopus Google Scholar). In adipoQ this is not and is by an Another for in that is important for the of and the of in the collagenous domain F. M. J. Biochem. 1992; PubMed Scopus Google Scholar, 1991; Full Text PDF PubMed Scopus Google Scholar) is also in adipoQ. In an in in a collagenous found in A and is in adipoQ. These have been to and mice and in a in the collagen that observed the H. J. PubMed Scopus Google Scholar, B. J. PubMed Scopus Google Scholar). These that adipoQ may have and from of an in and the adipoQ cDNA a protein of in is in with the molecular from the cDNA adipoQ is we a adipoQ and the that cells synthesized the adipoQ and the protein is secreted the Expression of the expression of adipoQ mRNA during in a mRNA of expressed in both 3T3-F442A and 3T3-L1 preadipocytes not in The expression of adipoQ mRNA found to during differentiation in both 3T3-F442A and 3T3-L1 cells A and with the expression of adipose differentiation such as lipoprotein P. Enerback S. Bjursell G. Olivecrona T. Pekala P.H. Biochem. J. 1988; 249: 765-769Crossref PubMed Scopus (99) Google Scholar) and P. Graves R.A. Spiegelman B.M. 1994; PubMed Scopus Google Scholar), the expression of adipoQ mRNA is a in at of is to or that of the mRNA and the expression of mRNA not is also that the adipoQ mRNA is a and in of adipoQ mRNA during at during adipose differentiation for both 3T3-F442A and 3T3-L1 of for to cDNA to lipoprotein and by to a for protein J. Res. 1991; PubMed Scopus Google Expression of in and the tissue of adipoQ we tissue from both mouse and A and A mRNA in mouse adipose tissue and adipoQ mRNA in tissues mRNA is at in adipose tissue in tissues in The of adipoQ mRNA in is also highly to adipose tissue in adipoQ of and in and these mRNA the or to A adipoQ mRNA also in a fat mouse adipoQ cDNA as a The expression of adipoQ mRNA in adipose tissue is highly to mature fat cells in and or expression in the stromal-vascular fraction isolated from fat and is with the adipoQ expression observed during differentiation in cell of adipoQ mRNA in tissues from and humans. of from mouse tissues by are as The to the adipoQ and the cDNA expression of adipoQ mRNA in of from tissues by to with two mature fat cell from fat and the stromal-vascular fraction of fat of adipoQ mRNA expression in and fat. of fat tissue by fat. used to of in and Adipose from and adipoQ gene expression is in obesity, we adipoQ mRNA levels in adipose tissue from and obese Fat from obese and also in a in adipoQ mRNA expression observed in fat tissue from the obese In the expression of not by A dramatic in mRNA expression observed in the mouse in with P. Spiegelman B.M. Science. 1987; PubMed Scopus Google Scholar). also adipoQ expression in fat from obese and A of in adipoQ mRNA observed in obese fat tissue as with the expression of adipoQ mRNA is clearly in of both mouse and of adipoQ mRNA in and obese fat from mice and humans. of from and obese mice fat by The with for and of fat from and obese for adipoQ expression. Expression of the 1 mRNA not in these and used as a for G.S. Arner P. Caro J.F. Atkinson R.L. Spiegelman B.M. J. Clin. Invest. 1995; 95: 2409-2415Crossref PubMed Scopus (2941) Google tissue to a for lipid and and to at the of and with for hormones such as and are expressed in adipose cells in and in P. MacDougald O.A. Lane M.D. Annu. Rev. Nutr. 1994; 14: 99-129Crossref PubMed Scopus (572) Google Scholar). recent that fat tissue is involved in the energy by molecules that signal to and the functions of tissues and B.M. Hotamisligil G.S. Cell. 1993; 73: 625-627Abstract Full Text PDF PubMed Scopus (199) Google Scholar, L.A. Smith F.J. Guisez Y. Devos R. Burn P. Science. 1995; 269: 546-549Crossref PubMed Scopus (3060) Google Scholar, Y. R. M. M. L. 1994; PubMed Scopus Google Scholar). of this is the of TNF-α by adipose tissue. is by fat cells in the of and G. Shargill N.S. Spiegelman B.M. Science. 1993; 259: 87-91Crossref PubMed Scopus (6031) Google Scholar). with insulin action in both and fat and plays a major role in insulin at in through a in the of the insulin G.S. Choy Spiegelman B.M. Proc. Natl. Acad. Sci. U. S. A. 1994; PubMed Scopus Google Scholar). Another is the obese gene The protein is synthesized by and is secreted the of this protein that or and L.A. Smith F.J. Guisez Y. Devos R. Burn P. Science. 1995; 269: 546-549Crossref PubMed Scopus (3060) Google Scholar, M. R.L. Science. 1995; 269: PubMed Scopus Google Scholar, R. T. F. Science. 1995; 269: PubMed Scopus Google Scholar). Another secreted molecule from adipose tissue with signaling is identified as an Min H.Y. Spiegelman B.M. Proc. Natl. Acad. Sci. U. S. A. 1985; PubMed Scopus Google Scholar), been to a of the complement J. T. Spiegelman B.M. Science. 1989; PubMed Scopus Google Scholar). the of this complement is to in adipose Rosen Spiegelman B.M. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar), molecules such as the that been to triglyceride in and A. A.D. S. M. B. J.C. A. S. J. Clin. Invest. 1993; PubMed Scopus Google Scholar). These that many important functions may through secreted from adipose adipoQ molecule identified in this that that function as a signaling molecule from adipocytes. adipoQ a signal sequence and is to secreted such as and collagen α1(X), and cerebellin. with adipoQ is secreted from of a expression the expression of adipoQ is highly during differentiation and is to adipose tissue in the expression of adipoQ is by in and a in this These of important signaling molecules secreted from adipose tissue the gene and these sequence and expression is to the functions of adipoQ. The sequence homology with a is the of the complement activation 1991; Full Text PDF PubMed Scopus Google Scholar). is of the and chain a collagenous (Gly-X-Y of amino acids and a globular region of amino A molecule subunits of chain the collagenous with the and the complement by and T. 1991; Full Text PDF PubMed Scopus Google Scholar). recent suggests that also functions such as B. J. 1978; Google Scholar), Frank M.M. A. J. 1987; Google Scholar), S. Y. J. 1988; Google Scholar), and G.S. G. B. J. 1987; Google Scholar) a A putative for been isolated and in and cells and A. J. 1990; Google Scholar). The collagenous region of been to important for R. S. J. 1990; PubMed Scopus Google Scholar, R. J. 1993; PubMed Scopus Google Scholar). and significant in the of this domain. is that adipoQ to the or a a biological is also that adipoQ may participate in the complement activation complement activation been to by a binding protein with a domain to that of T. N. T. J. Biol. Chem. 1987; Full Text PDF PubMed Google Scholar, J. S. H. R. J. 1990; Google Scholar, R. R. Science. 1991; PubMed Scopus Google Scholar). adipoQ in the that are important for is not adipoQ functions in complement to this of a novel adipose tissue-specific many molecular and that are to More biological role in adipose tissue and in the energy to The and of this novel protein a to adipose tissue in and this S. M. G. J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar) identified a protein a cDNA is to in protein INTRODUCTIONAdipose tissue is highly specialized to play important roles in energy storage, fatty acid metabolism, and glucose homeostasis(1.Cornelius P. MacDougald O.A. Lane M.D. Annu. Rev. Nutr. 1994; 14: 99-129Crossref PubMed Scopus (572) Google Scholar, 2.Spiegelman B.M. Choy L. Hotamisligil G.S. Graves R.A. Tontonoz P. J. Biol. Chem. 1993; 268: 6823-6826Abstract Full Text PDF PubMed Google Scholar). Adipocytes synthesize and store triglyceride in periods of nutritional abundance and mobilize the lipids in response to fasting(2.Spiegelman B.M. Choy L. Hotamisligil G.S. Graves R.A. Tontonoz P. J. Biol. Chem. 1993; 268: 6823-6826Abstract Full Text PDF PubMed Google Scholar, 3.Spiegelman B.M. Hotamisligil G.S. Cell. 1993; 73: 625-627Abstract Full Text PDF PubMed Scopus (199) Google Scholar). Fat tissue is also involved in regulating blood glucose levels through the expression of the insulin responsive glucose transporter, Glu4(4.Kaestner K.H. Christy R.J. McLenithan J.C. Braiterman L.T. Cornelius P. Pekala P.H. Lane M.D. Proc. Natl. Acad. Sci. U. S. A. 1989; 86: 3150-3154Crossref PubMed Scopus (248) Google Scholar, 5.Kaestner K.H. Christy R.J. Lane M.D. Proc. Natl. Acad. Sci. U. S. A. 1990; 87: 251-255Crossref PubMed Scopus (226) Google Scholar). Fat and muscle, in fact, constitute the two major sites for insulin-regulated glucose uptake.At a molecular level, many genes involved in lipid metabolism and glucose homeostasis are prominently expressed in fat(1.Cornelius P. MacDougald O.A. Lane M.D. Annu. Rev. Nutr. 1994; 14: 99-129Crossref PubMed Scopus (572) Google Scholar). These include fatty acid synthase(6.Moustaid N. Sul H.S. J. Biol. Chem. 1991; 266: 18550-18554Abstract Full Text PDF PubMed Google Scholar), the fatty acid binding protein aP2(7.Spiegelman B.M. Frank M. Green H. J. Biol. Chem. 1983; 258: 10083-10089Abstract Full Text PDF PubMed Google Scholar, 8.Hunt C.R. Ro J.H.-S. Dobson D.E. Min H.Y. Spiegelman B.M. Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 3786-3790Crossref PubMed Scopus (266) Google Scholar), lipoprotein lipase(9.Cornelius P. Enerback S. Bjursell G. Olivecrona T. Pekala P.H. Biochem. J. 1988; 249: 765-769Crossref PubMed Scopus (99) Google Scholar), phosphoenolpyruvate carboxykinase(10.Beale E.G. Tishler E.J. Biochem. Biophys. Res. Commun. 1992; 189: 925-930Crossref PubMed Scopus (13) Google Scholar), malic enzyme(11.Wise L.S. Sul H.S. Rubin C.S. J. Biol. Chem. 1984; 259: 4827-4832Abstract Full Text PDF PubMed Google Scholar), glyceraldehyde-3-phosphate dehydrogenase(12.Alexander M. Curtis G. Avruch J. Goodman H.M. J. Biol. Chem. 1985; 260: 11978-11985Abstract Full Text PDF PubMed Google Scholar), and Glut4 (4.Kaestner K.H. Christy R.J. McLenithan J.C. Braiterman L.T. Cornelius P. Pekala P.H. Lane M.D. Proc. Natl. Acad. Sci. U. S. A. 1989; 86: 3150-3154Crossref PubMed Scopus (248) Google Scholar). Receptors for lipogenic or lipolytic hormones such as insulin(13.Reed B.C. Lane M.D. Proc. Natl. Acad. Sci. U. S. A. 1980; 77: 285-289Crossref PubMed Scopus (161) Google Scholar, 14.Rubin C.S. Hirsch A. Fung C. Rosen O.M. J. Biol. Chem. 1978; 253: 7570-7578Abstract Full Text PDF PubMed Google Scholar), insulin-like growth factor 1(15.Campfield L.A. Smith F.J. Guisez Y. Devos R. Burn P. Science. 1995; 269: 546-549Crossref PubMed Scopus (3060) Google Scholar), and adrenergic compounds (16.Feve B. Emorine L.J. Briend-Sutren M.M. Lasnier F. Strosberg A.D. Pairault J. J. Biol. Chem. 1990; 265: 16343-16349Abstract Full Text PDF PubMed Google Scholar, 17.Guest S.J. Hadcock J.R. Watkins D.C. Malbon C.C. J. Biol. Chem. 1990; 265: 5370-5375Abstract Full Text PDF PubMed Google Scholar) are also expressed in adipocytes. In addition to these genes that clearly participate in the metabolic functions of adipose tissue, a group of genes that function in extracellular signaling have also been identified in fat. A prototype of these molecules is insulin-like growth factor 1, which is expressed in many tissues during development and plays an important role in cell proliferation(18.Froesch E.R. Schmid C. Schwander J. Zapf J. Annu. Rev. Physiol. 1985; 47: 443-467Crossref PubMed Google Scholar). In adipocytes, however, insulin-like growth factor 1 is found to stimulate cell differentiation(19.Smith P. Wise L.S. Berkowitz R. Wan C. Rubin C.S. J. Biol. Chem. 1988; 263: 9402-9408Abstract Full Text PDF PubMed Google Scholar). More interestingly, insulin-like growth factor 1 is synthesized by preadipocytes in response to growth hormone stimulation(20.Doglio A. Dani C. Fredrikson G. Grimaldi P. Ailhaud G. EMBO J. 1987; 6: 4011-4016Crossref PubMed Scopus (92) Google Scholar), thus potentially functioning in an autocrine or paracrine fashion to promote adipogenesis during development. Another signaling molecule from adipose tissue is TNF-α. 1The abbreviations used are: TNF-αtumor necrosis factor αDMEMDulbecco's modified Eagle's mediumPCRpolymerase chain reaction. TNF-α is secreted from fat, especially in obesity, and acts in an autocrine or paracrine manner to interfere with insulin action in fat and muscle(21.Hotamisligil G. Shargill N.S. Spiegelman B.M. Science. 1993; 259: 87-91Crossref PubMed Scopus (6031) Google Scholar, 22.Hotamisligil G.S. Arner P. Caro J.F. Atkinson R.L. Spiegelman B.M. J. Clin. Invest. 1995; 95: 2409-2415Crossref PubMed Scopus (2941) Google Scholar). The recent cloning and of the gene that adipose tissue signaling molecules that function in an Y. R. M. M. L. 1994; PubMed Scopus Google Scholar). The gene is secreted from fat the and acts to a putative in the region of the L.A. Smith F.J. Guisez Y. Devos R. Burn P. Science. 1995; 269: 546-549Crossref PubMed Scopus (3060) Google Scholar, Y. R. M. M. L. 1994; PubMed Scopus Google Scholar, M. R.L. Science. 1995; 269: PubMed Scopus Google Scholar). molecules secreted from adipose tissue are of functions in fat and thus a of adipose tissue this we have used mRNA differential display to a novel adipose gene termed adipoQ. suggests that adipoQ is a secreted protein that shares significant homology to subunits of complement factor and a collagenous at the and a globular domain at the The expression of this novel gene is highly during the adipose differentiation and is expressed in adipose tissue in a significant in adipoQ mRNA observed in fat tissues from obese mice and humans. a potentially molecular to the of adipose tissue in and