Protein: Adiponectin
Protein: Adiponectin
1. Introduction
Nowadays, obesity and its subsequent metabolic syndrome such as diabetes¸ atherosclerosis and heart disease [9], are threatening people's health world widely [3]. Effective treatment and drug are needed to solve these major health problems. In recent year, scientists found that a novel adipocytokine expression is associated with these diseases [8]. Adiponectin, an adipose tissue-specific protein [3], is a physiologically active product secreted by adipocyte and circulates in plasma [4]. It has been reported that in obesity and type 2 diabetes patients, plasma adiponectin levels decreased while it increased in chronic renal failure, type 1 diabetes and anorexia nervosa patients [3,7]. Adiponectin gene expression is inversely correlated with body mass index, and is at lower levels in obesity [3,5]. On the contrary, adiponectin is positively linked with insulin sensitizing action [2]. When drugs enhanced insulin sensitivity, an increase of plasma adiponectin and its mRNA levels could be found [5]. Adiponectin also has been reported that it shows ability of inhibiting inflammatory and atherogentic in vascular injury as a protector, which decreases adhesion molecules expression level in vascular endothelial cell during the early phases of atherosclerosis [5].
Since the biological functions of adiponectin play an important role in different major health problems, it may be a therapeutic tool for these diseases in the future. More and more studies for its gene and protein are required [3]. In this paper, the basic information of adiponectin structure and function will be investigated, and potential therapeutic applications will be discussed.
2. Methods
Online databases were used to investigate the structure and biological function of Adiponectin and predict its potential therapeutic application.
2.1 Investigation of expression and structure of Adiponectin gene
The key gene ID numbers and gene symbols of adiponectin were found in the NCBI OMIN website. The information of gene expression and structure are accessed by using the symbols in online databases. The Symatlas website, the NCBI GEO website and the LSBM website were used to check tissue which is adiponectin gene highly expressed. The location and structure data could be checked at the NCBI Entrez Gene website.
2.2 Investigation of structure and function of Adiponectin
Functional domains in adiponectin in human and mouse were predicted by using the Macrophages website. Information of difference among domain structures for splice variants could be found at the NCBI website. Functions of adiponectin of human and mouse isoform were compared through the UCSC website, and also could be found at the NCBI website. Known and predicted Interactions with other proteins were found at the HiMAP website.
2.3 Investigation of potential therapeutic application of Adiponectin
Phenotypic consequences of adiponectin gene knockout were looked through the Deltagen websie and reviewed by checking reference paper through the NCBI PubMed website. Potential drug target was predicted by considering all the information which is obtained.
3. Results
3.1 Expression and structure of Adiponectin gene
Adiponectin is product of ADIPOQ gene whose location in human is 3q27 on chromosome 3 and in mouse is 16 16.0 cM on chromosome 15. The ADIPOQ gene is highly expressed in adipocyte.
3.2 Structure and function of Adiponectin
The product of adiponectin gene is composed of a collagen-repeat domain at the N terminus and a C1q-like globular domain at the C terminus []. It is a member of the soluble defense collagen super family [10] and has structural homology with collagen VIII and X and complement factor C1q (figure1 and 2). Adiponectin could interact with other protein (figure3).
3.3 Potential therapeutic application of Adiponectin
In knockout studies, adiponectin-knockout mice experienced mild or moderate insulin resistance (lower level of insulin sensitivity) and increasing atherosclerosis. Adiponectin may have potential therapeutic application in obesity, type 2 diabetes and atherosclerosis [5].
4. Conclusions
Adiponectin is exclusively expressed and secreted by adipose tissue as an active adipocytokine [1]. According to the investigation of structure and function, adiponectin shows properties of inhibiting inflammatory and atherogenic. Its level in plasma is associated with insulin sensitivity. And the gene knockout study provided evidence for its positive effect on insulin sensitivity and atherosclerosis. Therefore, it can be predicted that adiponectin may play a role in therapeutic treatment to against diseases associated with insulin sensitivity, such as obesity and type 2 diabetes [8], and atherosclerosis, such as cardiovascular diseases [9].
5. References
- Christopher Q. Rogers, Joanne M. Ajmo and Min You. Adiponectin and Alcoholic Fatty Liver Disease. J. IUBMB Life 2008; 60(12): 790-797.
- J. NEDVíDKOVA, K. SMITKA, V. KOPSKY, V. HAINER. Adiponectin, an Adipocyte-Derived Protein. J. Physiol. Res. 2005; 54: 133-140.
- X. Fang and G. Sweeney. Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes. J. Biochemical Society Transactions 2006; 34: 798-801.
- Takashi Kadowaki , Toshimasa Yamauchi , Naoto Kubota. The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. J. FEBS Letters 2008; 582: 74-80.
- Juan J Diez and Pedro Iglesias. The role of the novel adipocyte-derived hormone adiponectin in human disease. J. European Journal of Endocrinology 2003: 148: 293-300.
- Kieren J. Mather , Tohru Funahashi , Yuji Matsuzawa , Sharon Edelstein , George A. Bray , Steven E. Kahn , Jill Crandall , Santica Marcovina , Barry Goldstein , and RonaldGoldberg Diabetes Prevention Program. Adiponectin, Change in Adiponectin, and Progression to Diabetes in the Diabetes Prevention Program. J. Diabetes 2008; 57(4): 980-986.
- Shoba Shetty, Christine M. Kusminski and Philipp E. Scherer. Adiponectin in health and disease: evaluation of adiponectin-targeted drug development strategies. J. Trends in Pharmacological Sciences 2009; 30: 34-39.
- WenfengTan, MD, PhD, FangWang, PhD, MiaojiaZhang, MD, DunmingGuo, MD, PhD, QiandeZhang, MD, and ShaohengHe, PhD. High Adiponectin and Adiponectin Receptor 1 Expression in Synovial Fluids and Synovial Tissues of Patients with Rheumatoid Arthritis. J. Semin Arthritis Rheum 2009; 38: 420-427.
- Rei Shibata, MD; Noriyuki Ouchi, MD; Toyoaki Murohara, MD. Adiponectin and Cardiovascular Disease. J. Circulation Journal 2009; 73: 608-614.
- Marta Garaulet, Juan J Hernandez-Morante, Fatima Perez de Heredia and Francisco J Tebar. Adiponectin, the controversial hormone. J. Public Health Nutrition 2007 10(10A): 1145-1150.
6. Appendix
The NCBI OMIN website:
Database and catalog of human genes and genetic disorders.
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605441
The NCBI GEO website :
Comparable experimental sample sets assembled from the Gene Expression Omnibus (GEO) repository.
http://www.ncbi.nlm.nih.gov/geo/
The LSBM website:
Database of all gene expression
http://www.lsbm.org/site_e/database/#
The NCBI Entrez Gene website:
Database of gene
http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene
The Symatlas website:
Database of gene function and structure
http://symatlas.gnf.org/deprecated/
The Macrophages website:
Database of macrophage and osteoclast biology
http://www.macrophages.com/bioinfoweb/
The UCSC website:
Database of genome browser, gene sorter, blat search function, and publications
http://genome.ucsc.edu/cgi-bin/hgGateway
The HiMAP website:
Database of known and predicted protein-protein interactions map
http://www.himap.org:80/main/index.jsp
The NCBI website:
Database of gene and protein sequence information
The Deltagen websie:
Drug discovery tool and database of gene function
The NCBI PubMed website:
Database of Medical life science journals
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed
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