Key points are not available for this paper at this time.
Chronic elevation of systemic levels of acute phase reactants and inflammatory cytokines found in patients with diabetes and the often-associated metabolic syndrome X (hypertriglyceridemia, low serum high density lipoprotein cholesterol, hypertension, and accelerated atherosclerosis) may be responsible for the increased incidence of cardiovascular problems in this population. Here we examine the contribution of adipose tissue to the systemic elevation of acute phase reactants associated with chronic hyperglycemia. We demonstrate that adipose tissue expresses a number of acute phase reactants at high levels, including serum amyloid A3 (SAA3), αl-acid glycoprotein, the lipocalin 24p3 as well as plasminogen activator inhibitor-1 (PAI-1). Additionally, we show SAA3 is expressed at low levels under normal conditions but in the diabetic state is dramatically up-regulated in adipose tissue while down-regulated in liver. Furthermore, pro-inflammatory stimuli and high glucose can lead to the induction of SAA3 in adipose tissue in vivo as well as in the 3T3-L1 adipocyte cell line. Adipose tissue may therefore play a major role in the pathogenic sequelae of Type II diabetes, in particular the cardiovascular problems associated with prolonged hyperglycemia. Chronic elevation of systemic levels of acute phase reactants and inflammatory cytokines found in patients with diabetes and the often-associated metabolic syndrome X (hypertriglyceridemia, low serum high density lipoprotein cholesterol, hypertension, and accelerated atherosclerosis) may be responsible for the increased incidence of cardiovascular problems in this population. Here we examine the contribution of adipose tissue to the systemic elevation of acute phase reactants associated with chronic hyperglycemia. We demonstrate that adipose tissue expresses a number of acute phase reactants at high levels, including serum amyloid A3 (SAA3), αl-acid glycoprotein, the lipocalin 24p3 as well as plasminogen activator inhibitor-1 (PAI-1). Additionally, we show SAA3 is expressed at low levels under normal conditions but in the diabetic state is dramatically up-regulated in adipose tissue while down-regulated in liver. Furthermore, pro-inflammatory stimuli and high glucose can lead to the induction of SAA3 in adipose tissue in vivo as well as in the 3T3-L1 adipocyte cell line. Adipose tissue may therefore play a major role in the pathogenic sequelae of Type II diabetes, in particular the cardiovascular problems associated with prolonged hyperglycemia. serum amyloid A3 lipopolysaccharide tumor necrosis factor α interleukin-6 plasminogen activator inhibitor-1 CCAAT/enhancer-binding protein reverse transcription polymerase chain reaction α1-acid glycoprotein adipose glucose uptake high density lipoprotein The central regulatory role of the adipocyte in whole body energy homeostasis is well established. However, pre-adipocytes and adipocytes may also play an important physiological role in the regulation of both the innate and adaptive immune response. We have recently described the response of the adipocyte to various inflammatory stimuli including TNFα and IL-6, focusing primarily on the response to bacterial lipopolysaccharides (LPS), which are mediated through the newly identified Toll-like receptor family (TLRs) (1Lin Y. Lee H. Berg A.H. Lisanti M.P. Shapiro L. Scherer P.E. J. Biol. Chem. 2000; 275: 24255-24263Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar). The expression of molecules involved in the innate immune response in adipose tissue, such as complement factors D (adipsin), B, and C3 (2White R.T. Damm D. Hancock N. Rosen B.S. Lowell B.B. Usher P. Flier J.S. Spiegelman B.M. J. Biol. Chem. 1992; 267: 9210-9213Abstract Full Text PDF PubMed Google Scholar, 3Choy L.N. Rosen B.S. Spiegelman B.M. J. Biol. Chem. 1992; 267: 12736-12741Abstract Full Text PDF PubMed Google Scholar, 4Cook K.S. Min H.Y. Johnson D. Chaplinsky R.J. Flier J.S. Hunt C.R. Spiegelman B.M. Science. 1987; 237: 402-405Crossref PubMed Scopus (286) Google Scholar) as well as acute phase reactant proteins (5Scherer P.E. Bickel P.E. Kotler M. Lodish H.F. Nat. Biotechnol. 1998; 16: 581-586Crossref PubMed Scopus (107) Google Scholar), has been demonstrated by our group as well as others. In addition, adipocytes actively secrete and respond to inflammatory cytokines such as TNFα, IL-1, and IL-6 (6Hotamisligil G.S. Shargill N.S. Spiegelman B.M. Science. 1993; 259: 87-91Crossref PubMed Scopus (6028) Google Scholar, 7Mattacks C.A. Pond C.M. Cytokine. 1999; 11: 334-346Crossref PubMed Scopus (72) Google Scholar, 8Mohamed-Ali V. Pinkney J.H. Coppack S.W. Int. J. Obes. Relat. Metab. Disord. 1998; 22: 1145-1158Crossref PubMed Scopus (794) Google Scholar). The latter two are primary cytokine mediators of the acute phase response. The transcription factors responsible for the downstream events of IL-1 and IL-6 include C/EBPβ as well as C/EBPδ, which are directly involved in the acute phase response of the liver (9Burgess-Beusse B.L. Darlington G.J. Mol. Cell. Biol. 1998; 18: 7269-7277Crossref PubMed Scopus (64) Google Scholar, 10Juan T.S. Wilson D.R. Wilde M.D. Darlington G.J. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 2584-2588Crossref PubMed Scopus (123) Google Scholar), typically considered the main contributor of circulating acute phase reactants. Because of the fact that adipocytes express significant levels of IL-1 and IL-6 receptors as well as high levels of C/EBPα, C/EBPβ, and C/EBPδ, it follows that adipocytes would be capable of producing high levels of acute phase reactant proteins in response to the proper stimuli (5Scherer P.E. Bickel P.E. Kotler M. Lodish H.F. Nat. Biotechnol. 1998; 16: 581-586Crossref PubMed Scopus (107) Google Scholar). However, the relative contribution of adipose tissue to systemic acute phase reactant levels, particularly in the diabetic state, has not been studied to date.Here we investigate the link between the inflammatory/acute phase reactant response and hyperglycemia/hyperinsulinemia at the level of the adipocyte. We show that hyperglycemia, but not hyperinsulinemia, leads to the induction and secretion of SAA3,1 an acute phase reactant in the adipocyte. Adipose tissue, and not the liver, may therefore be responsible for the increased SAA levels in the diabetic state reported in a number of clinical studies.DISCUSSIONThere is an increasing body of evidence that correlates the diabetic phenotype with chronically elevated systemic levels of acute phase reactants and inflammatory cytokines. It has been suggested that these elevated levels may contribute or be partially causative to some of the pathologies of the disease, in particular the increased incidence of cardiovascular problems. Pickup et al. (20Pickup J.C. Mattock M.B. Chusney G.D. Burt D. Diabetologia. 1997; 40: 1286-1292Crossref PubMed Scopus (1040) Google Scholar) show a correlation between the increased levels of several acute phase reactants and IL-6 and the metabolic syndrome X. These authors report elevated levels of circulating α1-acid glycoprotein and serum amyloid A. In addition, other groups show that fibrinogen, another acute phase reactant protein associated with coronary heart disease, is increased in Type II diabetes (21Kannel W.B. D'Agostino R.B. Wilson P.W. Belanger A.J. Gagnon D.R. Am. Heart J. 1990; 120: 672-676Crossref PubMed Scopus (318) Google Scholar, 22Ganda O.P. Arkin C.F. Diabetes Care. 1992; 15: 1245-1250Crossref PubMed Scopus (153) Google Scholar). Furthermore, elevated levels of complement factor C3 have also been reported in diabetic patients (23Figueredo A. Ibarra J.L. Bagazgoitia J. Rodriguez A. Molino A.M. Fernandez-Cruz A. Patino R. Diabetes Care. 1993; 16: 445-449Crossref PubMed Scopus (25) Google Scholar) as well as elevated levels of PAI-1 (24Yudkin J.S. J. Intern. Med. 1995; 238: 21-30Crossref PubMed Scopus (43) Google Scholar). Yokoyama et al.(25Yokoyama H. Jensen J.S. Jensen T. Deckert T. J. Intern. Med. 1995; 237: 519-523Crossref PubMed Scopus (49) Google Scholar) find that acute phase reactants are elevated in Type I diabetes, especially in albuminuric patients. Serum leptin concentrations are responsive to an acute phase or stress response, independent of body mass index (26Pickup J.C. Chusney G.D. Mattock M.B. Clin. Endocrinol. (Oxf). 2000; PubMed Scopus Google is that the in acute phase reactant some of which have to directly may contribute to the associated with serum amyloid increasing to with the of the liver to the for tissue J. Full Text PDF PubMed Google Scholar, 15: Full Text PDF PubMed Scopus Google Scholar). of demonstrate that inflammatory as serum amyloid and cytokines as are elevated at patients at for coronary Furthermore, clinical that the of for coronary heart disease, such as and may be in with the inflammatory 1999; Scholar). that elevated levels of in the of are associated with an increased of coronary events N. M. J.S. A.M. N. J. Med. PubMed Scopus Google Scholar). the level of protein independent of on levels, through an that these can also may therefore be in the primary of coronary events with low levels but with elevated levels of the acute reactant is the and of the inflammatory state and to hyperglycemia. However, our show that chronic low in the state for cardiovascular on the adipocyte as well as the the liver is as the major of of acute phase it has that adipose tissue may play a significant role in the systemic levels of these proteins in response to In to our focusing on adipocytes have been to express of complement factor C3 L.N. Rosen B.S. Spiegelman B.M. J. Biol. Chem. 1992; 267: 12736-12741Abstract Full Text PDF PubMed Google Scholar) and PAI-1 Biol. 1998; 18: PubMed Scopus Google is the report that at the of acute phase reactant proteins in adipose tissue and the associated with pro-inflammatory stimuli on these that α1-acid glycoprotein is expressed in as by the high of the and and P. also as is a glycoprotein and is of the major acute phase proteins in and with acute phase serum in response to systemic tissue or and these in serum protein concentrations have been with in T. D. 2000; PubMed Scopus Google Scholar). the levels of α1-acid glycoprotein and serum amyloid are by the factors in liver, we found regulation in adipose α1-acid glycoprotein is expressed at high levels, be by pro-inflammatory and expression is in the diabetic a regulation SAA3 and may a for high level expression in have to and factors may be associated with α1-acid glycoprotein a report by and J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) that with plasminogen activator and The authors that the of PAI-1 with play a role as an of the of the particularly or other acute phase The fact that both and PAI-1 are in adipose tissue is therefore not and it that would with PAI-1 and PAI-1 found that the lipocalin 24p3 is also expressed in adipose tissue and in the diabetic In to α1-acid glycoprotein, levels of 24p3 are low in 3T3-L1 to 24p3 can be by However, 24p3 is not by TNFα in 3T3-L1 24p3 has D.R. PubMed Scopus Google Scholar, J. PubMed Scopus Google Scholar, J. 1998; PubMed Scopus Google Scholar, Lee Mol. 2000; PubMed Scopus Google Scholar, M. S. M. PubMed Scopus Google Scholar, L. J.C. Google Scholar), the to as a to the for the protein has been to have for J. 1998; PubMed Scopus Google and A. P. 2000; Google Scholar) report an in SAA3 levels in the adipose tissue of with A. P. 2000; Google Scholar). In addition, also report 24p3 to be up-regulated to the as our the reported in we to the of 24p3 but a significant in 24p3 in the diabetic we the with to this are that can be the authors of the up-regulated in adipose tissue in the diabetic state the of inflammatory including the induction of acute phase reactants and several proteins that are the adipocytes and not the cell that are to proteins such as and that with the increased stress under In with the that are at elevated levels hyperglycemia, we found that the of is at the of the of SAA3 in adipose is that in not of the acute phase reactant family of proteins are in the as are in It is that the expression of some of these proteins a for under normal conditions to homeostasis as of an or have to molecules are associated with these proteins as of well described Furthermore, the that lead to the induction for the various acute phase reactants described in this have to be The central regulatory role of the adipocyte in whole body energy homeostasis is well established. However, pre-adipocytes and adipocytes may also play an important physiological role in the regulation of both the innate and adaptive immune response. We have recently described the response of the adipocyte to various inflammatory stimuli including TNFα and IL-6, focusing primarily on the response to bacterial lipopolysaccharides (LPS), which are mediated through the newly identified Toll-like receptor family (TLRs) (1Lin Y. Lee H. Berg A.H. Lisanti M.P. Shapiro L. Scherer P.E. J. Biol. Chem. 2000; 275: 24255-24263Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar). The expression of molecules involved in the innate immune response in adipose tissue, such as complement factors D (adipsin), B, and C3 (2White R.T. Damm D. Hancock N. Rosen B.S. Lowell B.B. Usher P. Flier J.S. Spiegelman B.M. J. Biol. Chem. 1992; 267: 9210-9213Abstract Full Text PDF PubMed Google Scholar, 3Choy L.N. Rosen B.S. Spiegelman B.M. J. Biol. Chem. 1992; 267: 12736-12741Abstract Full Text PDF PubMed Google Scholar, 4Cook K.S. Min H.Y. Johnson D. Chaplinsky R.J. Flier J.S. Hunt C.R. Spiegelman B.M. Science. 1987; 237: 402-405Crossref PubMed Scopus (286) Google Scholar) as well as acute phase reactant proteins (5Scherer P.E. Bickel P.E. Kotler M. Lodish H.F. Nat. Biotechnol. 1998; 16: 581-586Crossref PubMed Scopus (107) Google Scholar), has been demonstrated by our group as well as others. In addition, adipocytes actively secrete and respond to inflammatory cytokines such as TNFα, IL-1, and IL-6 (6Hotamisligil G.S. Shargill N.S. Spiegelman B.M. Science. 1993; 259: 87-91Crossref PubMed Scopus (6028) Google Scholar, 7Mattacks C.A. Pond C.M. Cytokine. 1999; 11: 334-346Crossref PubMed Scopus (72) Google Scholar, 8Mohamed-Ali V. Pinkney J.H. Coppack S.W. Int. J. Obes. Relat. Metab. Disord. 1998; 22: 1145-1158Crossref PubMed Scopus (794) Google Scholar). The latter two are primary cytokine mediators of the acute phase response. The transcription factors responsible for the downstream events of IL-1 and IL-6 include C/EBPβ as well as C/EBPδ, which are directly involved in the acute phase response of the liver (9Burgess-Beusse B.L. Darlington G.J. Mol. Cell. Biol. 1998; 18: 7269-7277Crossref PubMed Scopus (64) Google Scholar, 10Juan T.S. Wilson D.R. Wilde M.D. Darlington G.J. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 2584-2588Crossref PubMed Scopus (123) Google Scholar), typically considered the main contributor of circulating acute phase reactants. Because of the fact that adipocytes express significant levels of IL-1 and IL-6 receptors as well as high levels of C/EBPα, C/EBPβ, and C/EBPδ, it follows that adipocytes would be capable of producing high levels of acute phase reactant proteins in response to the proper stimuli (5Scherer P.E. Bickel P.E. Kotler M. Lodish H.F. Nat. Biotechnol. 1998; 16: 581-586Crossref PubMed Scopus (107) Google Scholar). However, the relative contribution of adipose tissue to systemic acute phase reactant levels, particularly in the diabetic state, has not been studied to Here we investigate the link between the inflammatory/acute phase reactant response and hyperglycemia/hyperinsulinemia at the level of the adipocyte. We show that hyperglycemia, but not hyperinsulinemia, leads to the induction and secretion of SAA3,1 an acute phase reactant in the adipocyte. Adipose tissue, and not the liver, may therefore be responsible for the increased SAA levels in the diabetic state reported in a number of clinical is an increasing body of evidence that correlates the diabetic phenotype with chronically elevated systemic levels of acute phase reactants and inflammatory cytokines. It has been suggested that these elevated levels may contribute or be partially causative to some of the pathologies of the disease, in particular the increased incidence of cardiovascular problems. Pickup et al. (20Pickup J.C. Mattock M.B. Chusney G.D. Burt D. Diabetologia. 1997; 40: 1286-1292Crossref PubMed Scopus (1040) Google Scholar) show a correlation between the increased levels of several acute phase reactants and IL-6 and the metabolic syndrome X. These authors report elevated levels of circulating α1-acid glycoprotein and serum amyloid A. In addition, other groups show that fibrinogen, another acute phase reactant protein associated with coronary heart disease, is increased in Type II diabetes (21Kannel W.B. D'Agostino R.B. Wilson P.W. Belanger A.J. Gagnon D.R. Am. Heart J. 1990; 120: 672-676Crossref PubMed Scopus (318) Google Scholar, 22Ganda O.P. Arkin C.F. Diabetes Care. 1992; 15: 1245-1250Crossref PubMed Scopus (153) Google Scholar). Furthermore, elevated levels of complement factor C3 have also been reported in diabetic patients (23Figueredo A. Ibarra J.L. Bagazgoitia J. Rodriguez A. Molino A.M. Fernandez-Cruz A. Patino R. Diabetes Care. 1993; 16: 445-449Crossref PubMed Scopus (25) Google Scholar) as well as elevated levels of PAI-1 (24Yudkin J.S. J. Intern. Med. 1995; 238: 21-30Crossref PubMed Scopus (43) Google Scholar). Yokoyama et al.(25Yokoyama H. Jensen J.S. Jensen T. Deckert T. J. Intern. Med. 1995; 237: 519-523Crossref PubMed Scopus (49) Google Scholar) find that acute phase reactants are elevated in Type I diabetes, especially in albuminuric patients. Serum leptin concentrations are responsive to an acute phase or stress response, independent of body mass index (26Pickup J.C. Chusney G.D. Mattock M.B. Clin. Endocrinol. (Oxf). 2000; PubMed Scopus Google is that the in acute phase reactant some of which have to directly may contribute to the associated with serum amyloid increasing to with the of the liver to the for tissue J. Full Text PDF PubMed Google Scholar, 15: Full Text PDF PubMed Scopus Google Scholar). of demonstrate that inflammatory as serum amyloid and cytokines as are elevated at patients at for coronary Furthermore, clinical that the of for coronary heart disease, such as and may be in with the inflammatory 1999; Scholar). that elevated levels of in the of are associated with an increased of coronary events N. M. J.S. A.M. N. J. Med. PubMed Scopus Google Scholar). the level of protein independent of on levels, through an that these can also may therefore be in the primary of coronary events with low levels but with elevated levels of the acute reactant is the and of the inflammatory state and to hyperglycemia. However, our show that chronic low in the state for cardiovascular on the adipocyte as well as the the liver is as the major of of acute phase it has that adipose tissue may play a significant role in the systemic levels of these proteins in response to In to our focusing on adipocytes have been to express of complement factor C3 L.N. Rosen B.S. Spiegelman B.M. J. Biol. Chem. 1992; 267: 12736-12741Abstract Full Text PDF PubMed Google Scholar) and PAI-1 Biol. 1998; 18: PubMed Scopus Google is the report that at the of acute phase reactant proteins in adipose tissue and the associated with pro-inflammatory stimuli on these that α1-acid glycoprotein is expressed in as by the high of the and and P. also as is a glycoprotein and is of the major acute phase proteins in and with acute phase serum in response to systemic tissue or and these in serum protein concentrations have been with in T. D. 2000; PubMed Scopus Google Scholar). the levels of α1-acid glycoprotein and serum amyloid are by the factors in liver, we found regulation in adipose α1-acid glycoprotein is expressed at high levels, be by pro-inflammatory and expression is in the diabetic a regulation SAA3 and may a for high level expression in have to and factors may be associated with α1-acid glycoprotein a report by and J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) that with plasminogen activator and The authors that the of PAI-1 with play a role as an of the of the particularly or other acute phase The fact that both and PAI-1 are in adipose tissue is therefore not and it that would with PAI-1 and PAI-1 found that the lipocalin 24p3 is also expressed in adipose tissue and in the diabetic In to α1-acid glycoprotein, levels of 24p3 are low in 3T3-L1 to 24p3 can be by However, 24p3 is not by TNFα in 3T3-L1 24p3 has D.R. PubMed Scopus Google Scholar, J. PubMed Scopus Google Scholar, J. 1998; PubMed Scopus Google Scholar, Lee Mol. 2000; PubMed Scopus Google Scholar, M. S. M. PubMed Scopus Google Scholar, L. J.C. Google Scholar), the to as a to the for the protein has been to have for J. 1998; PubMed Scopus Google and A. P. 2000; Google Scholar) report an in SAA3 levels in the adipose tissue of with A. P. 2000; Google Scholar). In addition, also report 24p3 to be up-regulated to the as our the reported in we to the of 24p3 but a significant in 24p3 in the diabetic we the with to this are that can be the authors of the up-regulated in adipose tissue in the diabetic state the of inflammatory including the induction of acute phase reactants and several proteins that are the adipocytes and not the cell that are to proteins such as and that with the increased stress under In with the that are at elevated levels hyperglycemia, we found that the of is at the of the of SAA3 in adipose is that in not of the acute phase reactant family of proteins are in the as are in It is that the expression of some of these proteins a for under normal conditions to homeostasis as of an or have to molecules are associated with these proteins as of well described Furthermore, the that lead to the induction for the various acute phase reactants described in this have to be is an increasing body of evidence that correlates the diabetic phenotype with chronically elevated systemic levels of acute phase reactants and inflammatory cytokines. It has been suggested that these elevated levels may contribute or be partially causative to some of the pathologies of the disease, in particular the increased incidence of cardiovascular problems. Pickup et al. (20Pickup J.C. Mattock M.B. Chusney G.D. Burt D. Diabetologia. 1997; 40: 1286-1292Crossref PubMed Scopus (1040) Google Scholar) show a correlation between the increased levels of several acute phase reactants and IL-6 and the metabolic syndrome X. These authors report elevated levels of circulating α1-acid glycoprotein and serum amyloid A. In addition, other groups show that fibrinogen, another acute phase reactant protein associated with coronary heart disease, is increased in Type II diabetes (21Kannel W.B. D'Agostino R.B. Wilson P.W. Belanger A.J. Gagnon D.R. Am. Heart J. 1990; 120: 672-676Crossref PubMed Scopus (318) Google Scholar, 22Ganda O.P. Arkin C.F. Diabetes Care. 1992; 15: 1245-1250Crossref PubMed Scopus (153) Google Scholar). Furthermore, elevated levels of complement factor C3 have also been reported in diabetic patients (23Figueredo A. Ibarra J.L. Bagazgoitia J. Rodriguez A. Molino A.M. Fernandez-Cruz A. Patino R. Diabetes Care. 1993; 16: 445-449Crossref PubMed Scopus (25) Google Scholar) as well as elevated levels of PAI-1 (24Yudkin J.S. J. Intern. Med. 1995; 238: 21-30Crossref PubMed Scopus (43) Google Scholar). Yokoyama et al.(25Yokoyama H. Jensen J.S. Jensen T. Deckert T. J. Intern. Med. 1995; 237: 519-523Crossref PubMed Scopus (49) Google Scholar) find that acute phase reactants are elevated in Type I diabetes, especially in albuminuric patients. Serum leptin concentrations are responsive to an acute phase or stress response, independent of body mass index (26Pickup J.C. Chusney G.D. Mattock M.B. Clin. Endocrinol. (Oxf). 2000; PubMed Scopus Google Scholar). It is that the in acute phase reactant some of which have to directly may contribute to the associated with serum amyloid increasing to with the of the liver to the for tissue J. Full Text PDF PubMed Google Scholar, 15: Full Text PDF PubMed Scopus Google Scholar). of demonstrate that inflammatory as serum amyloid and cytokines as are elevated at patients at for coronary Furthermore, clinical that the of for coronary heart disease, such as and may be in with the inflammatory 1999; Scholar). that elevated levels of in the of are associated with an increased of coronary events N. M. J.S. A.M. N. J. Med. PubMed Scopus Google Scholar). the level of protein independent of on levels, through an that these can also may therefore be in the primary of coronary events with low levels but with elevated levels of the acute reactant is the and of the inflammatory state and to hyperglycemia. However, our show that chronic low in the state for cardiovascular on the adipocyte as well as the liver. the liver is as the major of of acute phase it has that adipose tissue may play a significant role in the systemic levels of these proteins in response to In to our focusing on adipocytes have been to express of complement factor C3 L.N. Rosen B.S. Spiegelman B.M. J. Biol. Chem. 1992; 267: 12736-12741Abstract Full Text PDF PubMed Google Scholar) and PAI-1 Biol. 1998; 18: PubMed Scopus Google Scholar). is the report that at the of acute phase reactant proteins in adipose tissue and the associated with pro-inflammatory stimuli on these that α1-acid glycoprotein is expressed in as by the high of the and and P. also as is a glycoprotein and is of the major acute phase proteins in and with acute phase serum in response to systemic tissue or and these in serum protein concentrations have been with in T. D. 2000; PubMed Scopus Google Scholar). the levels of α1-acid glycoprotein and serum amyloid are by the factors in liver, we found regulation in adipose α1-acid glycoprotein is expressed at high levels, be by pro-inflammatory and expression is in the diabetic a regulation SAA3 and may a for high level expression in have to and factors may be associated with α1-acid glycoprotein a report by and J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) that with plasminogen activator and The authors that the of PAI-1 with play a role as an of the of the particularly or other acute phase The fact that both and PAI-1 are in adipose tissue is therefore not and it that would with PAI-1 and PAI-1 We found that the lipocalin 24p3 is also expressed in adipose tissue and in the diabetic In to α1-acid glycoprotein, levels of 24p3 are low in 3T3-L1 to 24p3 can be by However, 24p3 is not by TNFα in 3T3-L1 24p3 has D.R. PubMed Scopus Google Scholar, J. PubMed Scopus Google Scholar, J. 1998; PubMed Scopus Google Scholar, Lee Mol. 2000; PubMed Scopus Google Scholar, M. S. M. PubMed Scopus Google Scholar, L. J.C. Google Scholar), the to as a to the for the protein has been to have for J. 1998; PubMed Scopus Google Scholar). and A. P. 2000; Google Scholar) report an in SAA3 levels in the adipose tissue of with A. P. 2000; Google Scholar). In addition, also report 24p3 to be up-regulated to the as our the reported in we to the of 24p3 but a significant in 24p3 in the diabetic we the with to this are that can be the authors of the up-regulated in adipose tissue in the diabetic state the of inflammatory including the induction of acute phase reactants and several proteins that are the adipocytes and not the cell that are to proteins such as and that with the increased stress under In with the that are at elevated levels hyperglycemia, we found that the of is at the of the of SAA3 in adipose is that in not of the acute phase reactant family of proteins are in the as are in It is that the expression of some of these proteins a for under normal conditions to homeostasis as of an or have to molecules are associated with these proteins as of well described Furthermore, the that lead to the induction for the various acute phase reactants described in this have to be We of the Scherer especially for with the in vivo We also for and for with the diabetic and and for
Lin et al. (Thu,) studied this question.