Professor A Xu
Professor
Department of Pharmacology & Pharmacy, The University of Hong Kong
Professor
Professor Aimin Xu (徐愛民)
BMed Anhui, MSc, PhD Auck
American Diabetes Association
American society of Biochemistry and Molecular Biology HBHA center, HKU
Editor, Biochemical Journal, Clinical Sciences, PLOS ONE
Obesity is a major risk factor for diabetes and cardiovascular disease (CVD). In obese adipose tissue, enlarged adipocytes are infiltrated with activated macrophages, both of which secrete a large number of pro-inflammatory adipokines involved in insulin resistance, endothelial dysfunction and cardiac remodeling. By contrast, the adipocyte production of adiponectin, an insulin-sensitizing adipokine with anti-inflammatory properties, is decreased in obese subjects. Aberrant production of adipokines from adipose tissue is now recognized as an important mediator that links obesity with its medical complications. The primary research focus of our laboratory is to comprehensively study the pathological roles of adipokines in the development of obesity-related insulin resistance, systemic inflammation, diabetes and vascular dysfunctions, from molecular and cellular levels to animal models and human subjects. Our long-term objective is to develop adipokine-based diagnostics and therapeutics for risk prediction and prevention of obesity-induced diabetes and CVD.
Professor Xu and his research associates (click image to enlarge)
- Basic research:
Roles of adipokines in the pathogenesis of endothelial dysfunction and atherosclerosis. We are particularly interested in adiponectin and adipocyte fatty acid binding protein (A-FABP), the two major adipokines produced from adipose tissue. We have recently identified APPL1, an intracellular adaptor protein, as a key signaling relay that mediates adiponectin-induced activation of eNOS and NO production in endothelial cells. Our ongoing projects on adiponectin include (1) investigating the detailed receptor and postreceptor signaling mechanisms involved in its endothelium actions; (2) elucidating the role of adiponectin in regulating endothelial regeneration in obese/diabetic animal models. In addition, we are using the transgenesis approach to investigate the role of A-FABP in the initiation and progression of endothelial dysfunction and vascular inflammation in animal models of obesity and diabetes.
- Applied research:
Adipocytes as a source for biomarker discovery and drug development. We have generated several lines of transgenic mice with adipose tissue-selective inactivation of the key inflammatory pathways, which allow us to address whether or not genetic intervention of adipokine production alone is sufficient to alleviate obesity-related systemic inflammation, insulin resistance and vascular dysfunction. Using proteomics and functional genomics-based approaches, we have recently identified and characterized several novel adipokines from adipocytes. We are now using these adipokines as biomarkers for high throughput screening of new compounds from medicinal herbs with anti-diabetic and vasculo-protective properties.
- Clinical research:
Evaluation of serum adipokines as biomarkers for risk prediction, early diagnosis and therapeutic monitoring of diabetes and vascular disease in Chinese population. With the support from Hong Kong Innovation & Technology fund, we have developed a proprietary monoclonal antibody-based multiplex immunoassay for simultaneous analysis of up to eight adipokines in a small volume of blood samples. We are now using this assay to conduct several large scale population-based studies in Hong Kong and Mainland China to investigate the cross-sectional and prospective associations of serum levels of several key adipokines and diabetes and cardiovascular disease. In addition, we have established an antibody and immunoassay service center in HKU to help local and overseas researchers for biomarker discovery, assay development, and clinical validations (see our website: www.antibody.hku.hk). So far, we have developed over 20 immunoassay products that can be used for basic and clinical research, drug screening and diagnostics.
Cheng KK, Lam KS, Wu D, Wang Y.. and Xu A*. APPL1 potentiates insulin secretion in pancreatic beta-cells by increasing Akt-dependent expression of SNARE proteins in mice. Proc. Natl. Acad. Sci. USA, 2012, 109:8919-24, selected for commentary.
Li FY, Lam KS, Tse HF, Chen C, Wang Y, Vanhoutte PM, Xu A*. Endothelium-selective activation of AMP-activated protein kinase prevents diabetes mellitus-induced impairment in vascular function and reendothelialization via induction of heme oxygenase-1 in mice. Circulation. 2012, 126:1267-77.
Tian XY, Wong WT, Xu A*, Lu Y, Zhang Y, Wang L, Cheang WS, Wang Y, Yao X, Huang Y. Uncoupling Protein-2 Protects Endothelial Function in Diet-induced Obese Mice. Circ Res. 2012, 110:1211-6.
Ye D, Li Y, Lam KS, Li H, Jia W, Wang Y, Man K, Li X and Xu A*. TLR4 mediates obesity-induced nonalcoholic steatohepatitis through activation of X-box binding protein in mice. Gut. 2012, 61: 1058-67
Wang Y, Cheng KK, Lam KS, Wu D, Wang Y, Huang Y, Vanhoutte PM, Sweeney G, Li Y, Xu A*. APPL1 counteracts obesity-induced vascular insulin resistance and endothelial dysfunction by modulating the endothelial production of nitric oxide and endothelin-1 in mice. Diabetes, 2011, 60: 3044-54.
Chen W, Hoo RL, Konishi M, Itoh N, Lee PC, Ye HY, Lam KS, Xu A*. Growth hormone induces hepatic production of fibroblast growth factor 21 through a mechanism dependent on lipolysis in adipocytes. J. Biol. Chem, 2011, 286:34559-66.
Wong WT, Tian XY, Xu A*, Yu J, Lau CW, Hoo R, Wang Y, Lee VW, Lam KS, Vanhoutte PM, and Huang Y. The obligatory role of adiponectin in restoring endothelial function in PPARγ agonist-treated diabetic mice. Cell Metabolism, 2011, 16:101-15.
Chang J , Li Y , Huang Y , Lam KS, Hoo LC, Wong WT, Cheng KK, Wang Y, Vanhoutte PM , and Xu A*. Adiponectin Prevents Diabetic Premature Senescence of Endothelial Progenitor Cells and Promotes Endothelial Repair by Suppressing the p38 MAP kinase/p16INK4A Signaling Pathway. Diabetes, 2010, 59: 2949-59
Hui X, Li H, Zhou Z, Lam KS, Xiao Y, Wu D, Ding K, Wang Y, Vanhoutte PM and Xu A*. Adipocyte fatty acid binding protein mediates inflammatory responses in macrophages through a positive feedback loop involving c-Jun N-terminal kinases and activator protein-1. J. Biol. Chem, 2010, 285: 10273-80
Cheng KK, Iglesias MA, Lam KS, Wang Y, Sweeney, Zhu W, Vanhoutte PM, Kraegen EW and Xu A*. APPL1 Potentiates Insulin-mediated Inhibition of Hepatic Glucose Production and Alleviates Diabetes via Akt Activation in Mice. Cell Metabolism, 2009, 9:417-27.
Zhang X, Yeung DC, Karpisek M, Stejskal D, Zhou ZG, Liu F, Wong RL, Chow WS, Tso AW, Lam KS, Xu A*. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes, 2008, 57:1246-53
Xu A*, Lam MCL, Chan KW, Wang Y, Hoo RCL, Zhang JL, Tso A and Lam KSL, ANGPTL4 decreases blood glucose, improve glucose tolerance, but induces hyperlipidemia and hepatic steatosis in mice, Proc. Natl. Acad. Sci. USA, 2005, 102, 6089-6091
Xu A*, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J. Clin. Invest. 2003, 112:91-100.The paper was selected for the cover story of this issue.
Professor A Xu
Office:
8/F, 21 Sassoon Road, Li Ka Shing Faculty of Medicine, Laboratory Block, Faculty of Medicine Building, Hong Kong SAR, China.
Email: amxu@hku.hk
Dr. Gary Sweeney, York University, Canada.
Prof. Edward Kraegen, Garvin's institute, Australia.
Prof. Jia Weiping, Shanghai Diabetes Center, China
2012 -
Theme-based Research Scheme (T12-705/11) - Co-I
- Personalized medicine for cardiovascular diseases
General Research Fund (784111M) -PI
- The Liver-derived Hormone FGF21 as a Novel Regulator of Vascular Function: Molecular Basis and Physiological Implications
2011 -
RGC collaborative research fund (HKU4/CRF/10) -PI
-
A multiple disciplinary approach to investigate vascular dysfunction in obesity and diabetes: From molecular mechanism to therapeutic intervention
National "973" basic research on diabetes matching fund (2011CB504004) -PI
- 2型糖尿病发生发展的分子机制研究 (Molecular basis of type 2 diabetes).
General Research Fund (783010M) -PI
- APPL2 as a Negative Regulator of Insulin Sensitivity and Glucose Uptake in Skeletal Muscle: A Novel Pathway Leading to Insulin Resistance?
2010 -
RGC collaborative Research Fund (HKU 3/CRF/09) - Co-I
- To Establish a Metabolic Study Center in Hong Kong: Focusing on the liver-derived hormones
General Research fund (781309M) -PI
- Characterization of Novel Adaptor Proteins Involved in Regulating Insulin Sensitivity and Glucose Homeostasis: from Molecular Mechanism to Physiological Implication
2009-
NSFC/RGC joint research scheme 2008 (NHKU 735_08) -PI
- Adipocyte fatty acid binding protein as a novel diagnostic marker and therapeutic target to combat vascular complications of diabetes: mechanisms and clinical implications
General Research Fund 2008 (779608M) -PI
- Protective roles of AMP-activated protein kinase against vascular disease in diabetes: Molecular mechanisms and therapeutic intervention
Antibody and Immunoassay Services