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1.
Obesity (Silver Spring) ; 15(9): 2225-32, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17890490

ABSTRACT

OBJECTIVE: Retinol binding protein-4 (RBP4) has been reported to impair insulin sensitivity throughout the body. We investigated the relationship between serum RBP4 levels and adiposity indices as well as metabolic risk variables. RESEARCH METHODS AND PROCEDURE: We recruited a total of 102 healthy women 21 to 67 years old. We assessed body composition by computed tomography and divided the study population into four groups based on body weight and visceral fat area (non-obese without visceral adiposity, non-obese with visceral adiposity, obese without visceral adiposity, and obese with visceral adiposity). Serum RBP4 levels were measured by radioimmunoassay. RESULTS: Despite similar levels of total body fat, non-obese women had lower systolic blood pressure, total cholesterol, triglyceride (TG), low-density lipoprotein (LDL)-cholesterol levels, insulin resistance indices, and RBP4 levels than non-obese women with visceral adiposity and had higher high-density lipoprotein-cholesterol levels. Similarly, obese women without visceral adiposity had lower blood pressure, total cholesterol, TG levels, insulin resistance indices, and RBP4 levels than obese women with visceral adiposity. In addition, despite having increased body fat, obese women without visceral adiposity had lower TGs, insulin resistance indices, and serum RBP4 levels than non-obese women with visceral adiposity. By step-wise multiple regression analysis, visceral fat areas and LDL-cholesterol levels independently affected RBP4 levels. DISCUSSION: We determined that serum RBP4 levels are independently associated with visceral fat and LDL-cholesterol levels. These results suggest that, irrespective of body weight, visceral obesity is an independent predictor of serum RBP4 levels, and RBP4 may represent a link between visceral obesity and cardiovascular disease.


Subject(s)
Intra-Abdominal Fat/metabolism , Retinol-Binding Proteins, Plasma/biosynthesis , Adipokines/metabolism , Adiposity , Adult , Aged , Body Weight , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Cholesterol/metabolism , Female , Humans , Insulin Resistance , Middle Aged , Obesity , Regression Analysis , Risk , Risk Factors
3.
Drug News Perspect ; 17(5): 293-8, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15334178

ABSTRACT

It is becoming clear that adipose tissue is not merely a storage for excess energy but that it secretes a number of biologically active soluble factors collectively termed adipocytokines that control glucose and fatty acid metabolism. Of these adipocytokines, adiponectin and resistin have been the objects of intensive research, as they are implicated in obesity and diabetes-related diseases. In this review, we summarize recent advances in understanding the roles of adiponectin and resistin in the causation of metabolic diseases and consider the prospects for treating metabolic disorders by targeting these two adipocytokines.


Subject(s)
Adipocytes/metabolism , Hormones, Ectopic/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Adipocytes/pathology , Adiponectin , Animals , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Glucose/metabolism , Humans , Intercellular Signaling Peptides and Proteins/genetics , Obesity/complications , Obesity/metabolism , Resistin
4.
Clin Diagn Lab Immunol ; 11(3): 446-51, 2004 May.
Article in English | MEDLINE | ID: mdl-15138168

ABSTRACT

Listeria monocytogenes causes major food-borne outbreaks of disease worldwide. Specific identification of this microorganism is of utmost importance to public health and industry. Listeria species are known to secrete a 60-kDa protein collectively termed p60, which is encoded by the iap (invasion-associated protein) gene and secreted in large quantities into the growth media. p60 is a highly immunogenic murein hydrolase that is essential for cell division. Due to these properties, p60 is an ideal diagnostic target for the development of immunological detection systems for L. monocytogenes. We report here two independent lines of monoclonal antibody (MAb): p6007, which specifically recognizes L. monocytogenes p60, and p6017, which reacts with a wide range of Listeria p60 proteins. By combining these antibodies with a polyclonal antibody, we developed efficient sandwich enzyme-linked immunosorbent assay (ELISA) systems which can specifically identify L. monocytogenes or generally detect Listeria species. Since an excess amount of the peptide corresponding to PepA or PepD did not interfere with the ELISA, and direct ELISAs were unable to detect both peptides, we concluded that the epitope presumed to be recognized by p6007 or p6017 could be distinguished from PepA and PepD as described by Bubert et al. (Appl. Environ. Microbiol. 60:3120-3127, 1997). To our best knowledge, this is the first example of an immunological identification system that uses p60-recognizing MAbs.


Subject(s)
Antibodies, Monoclonal/immunology , Bacterial Proteins/immunology , Listeria monocytogenes/immunology , Animals , Antibodies/immunology , Antibodies/isolation & purification , Antibodies, Monoclonal/isolation & purification , Antibody Specificity/immunology , Antigen-Antibody Reactions/immunology , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Epitopes/immunology , Escherichia coli/genetics , Escherichia coli/immunology , Feces/microbiology , Hybridomas/immunology , Lipoproteins/immunology , Listeria/immunology , Listeria/isolation & purification , Listeria monocytogenes/genetics , Listeria monocytogenes/isolation & purification , Mice , Mice, Inbred BALB C , Rabbits , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Species Specificity , Vaccination
5.
J Biol Chem ; 279(21): 22108-17, 2004 May 21.
Article in English | MEDLINE | ID: mdl-15037635

ABSTRACT

Adiponectin is exclusively expressed in differentiated adipocytes and plays an important role in regulating energy homeostasis, including the glucose and lipid metabolism associated with increased insulin sensitivity. However, the control of adiponectin gene expression in adipocytes is poorly understood. We show here that levels of adiponectin mRNA and protein are reduced in the white adipose tissue of ob/ob and db/db mice and that there is a concomitant reduction of the adipocyte determination- and differentiation-dependent factor 1 (ADD1)/sterol regulatory element-binding protein 1c (SREBP1c) transcription factor. To determine whether ADD1/SREBP1c regulates adiponectin gene expression, we isolated and characterized the mouse adiponectin promoter. Analysis of the adiponectin promoter revealed putative binding sites for the adipogenic transcription factors ADD1/SREBP1c, peroxisomal proliferator-activated receptor gamma and CCAAT enhancer-binding proteins. DNase I footprinting and chromatin immunoprecipitation analyses revealed that ADD1/SREBP1c binds in vitro and in vivo to the proximal promoter containing sterol regulatory element (SRE) motifs. A luciferase reporter containing the promoter was transactivated by ADD1/SREBP1c, and introduction of SRE mutations into the construct abolished transactivation. Adenoviral overexpression of ADD1/SREBP1c also elevated adiponectin mRNA and protein levels in 3T3-L1 adipocytes. Furthermore, insulin stimulated adiponectin mRNA expression in adipocytes and augmented transactivation of the adiponectin promoter by ADD1/SREBP1c. Taken together, these data indicate that ADD1/SREBP1c controls adiponectin gene expression in differentiated adipocytes.


Subject(s)
Adipocytes/metabolism , CCAAT-Enhancer-Binding Proteins/physiology , DNA-Binding Proteins/physiology , Gene Expression Regulation , Intercellular Signaling Peptides and Proteins , Protein Biosynthesis , 3T3-L1 Cells , Adenoviridae/genetics , Adiponectin , Amino Acid Motifs , Animals , Binding Sites , Blotting, Northern , Blotting, Western , CCAAT-Enhancer-Binding Proteins/metabolism , Cell Differentiation , Cell Line , Chromatin/metabolism , Cloning, Molecular , DNA-Binding Proteins/metabolism , Deoxyribonuclease I/metabolism , Luciferases/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Mice, Transgenic , Models, Genetic , Precipitin Tests , Promoter Regions, Genetic , Protein Binding , Proteins/metabolism , RNA, Messenger/metabolism , Rats , Receptors, Cytoplasmic and Nuclear/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sterol Regulatory Element Binding Protein 1 , Transcription Factors/metabolism , Transfection
6.
Biochem Biophys Res Commun ; 310(2): 433-8, 2003 Oct 17.
Article in English | MEDLINE | ID: mdl-14521928

ABSTRACT

Glucocorticoid-induced tumor necrosis receptor (GITR) has been implicated in regulation of T cell suppression by CD25(+)CD4(+) regulatory T cells (Tregs). We isolated a cDNA encoding GITR ligand (GITRL) from mouse endothelioma cells. When stably expressed in HEK293 cells, its specific interaction with GITR was confirmed by flow cytometry with the use of GITR-Fc. The interaction was greatly diminished by the addition of soluble GITRL. Consistent with this, soluble GITRL bound to the cell surface of the GITR-expressing HEK293 cells. Coexpression of GITR with GITRL or stimulation of the GITR-expressing cells with soluble GITRL led to activation of NF-kappaB, which was significantly reduced by anti-GITR. More importantly, GITRL was expressed by both immature and mature dendritic cells, suggesting that the interaction between GITR and GITRL may contribute to immune regulation of Tregs by dendritic cells. This isolated TNFRL represents a bona fide GITRL whose presence has been elusive until this time.


Subject(s)
Carrier Proteins/metabolism , Dendritic Cells/immunology , Receptors, Nerve Growth Factor/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Tumor Necrosis Factors , Amino Acid Sequence , Animals , Carrier Proteins/chemistry , Cell Line , Cell Line, Tumor , Glucocorticoid-Induced TNFR-Related Protein , Ligands , Mice , Molecular Sequence Data , Sequence Alignment
7.
Blood ; 99(12): 4413-21, 2002 Jun 15.
Article in English | MEDLINE | ID: mdl-12036870

ABSTRACT

The transmembrane 4 superfamily (TM4SF) has come into prominence for its association with a wide range of cell surface molecules, especially integrins. We report that TM4SF molecules CD9, CD63, and CD81 are physically associated with c-kit receptor tyrosine kinase in the human factor-dependent myeloid cell line, MO7e. We characterized this complex using coimmunoprecipitation and colocalization methods. The c-kit coimmunoprecipitated with anti-TM4SF antibodies showed several distinct phenotypes compared to the total c-kit immunoprecipitated with anti-c-kit antibody. These included: (1) higher basal level of tyrosine phosphorylation without elevated kinase activity in the absence of Steel factor (SLF), (2) deficient enhancement of tyrosine phosphorylation and kinase activity in response to SLF, (3) elevated binding rate of SLF shown in chemical cross-linking studies, and (4) little internalization and degradation after SLF treatment. Cocapping studies in living cells showed that c-kit colocalized with TM4SF molecules after SLF stimulation, suggesting confirmation of the biochemical data obtained by the coimmunoprecipitation studies. Colocalization of c-kit with CD81 by SLF was also observed in cord blood CD34(+) cells, suggesting the existence of functional units of c-kit in TM4SF complexes in primary hematopoietic cells. This suggests that some TM4SF members may negatively modulate function of c-kit receptor tyrosine kinase and thus regulate receptor sensitivity to SLF in hematopoietic progenitors.


Subject(s)
Hematopoietic Stem Cells/metabolism , Membrane Glycoproteins , Membrane Proteins/metabolism , Proto-Oncogene Proteins c-kit/metabolism , Antigens, CD/metabolism , Antigens, CD/physiology , Cell Line , Fetal Blood/cytology , Hematopoietic Stem Cells/chemistry , Humans , Membrane Proteins/physiology , Multigene Family , Phosphorylation/drug effects , Platelet Membrane Glycoproteins/metabolism , Platelet Membrane Glycoproteins/physiology , Precipitin Tests , Protein Binding/drug effects , Proto-Oncogene Proteins c-kit/drug effects , Stem Cell Factor/pharmacology , Tetraspanin 28 , Tetraspanin 29 , Tetraspanin 30
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