Aimin Xu　教授

Professor Aimin Xu (徐愛民)

BMed Anhui, MSc, PhD Auck

Director, State Key Laboratory of Pharmaceutical Biotechnology, HKU 

(www.sklpb.hku.hk)

Director, Antibody and Immunoassay Services, HKU 

(www.antibody.hku.hk)

Memberships:

Deputy Chair, Biochemical Journal

American Diabetes Association

American society of Biochemistry and Molecular Biology HBHA center, HKU

Editorships:

Editor: Clinical Science, PLOS One

Editorial Board member, Journal of Obesity, Journal of Diabetes, Adipocytes, Cardiovascular

Drugs and Therapy Editor

My Research Interests

Obesity is a major risk factor of type 2 diabetes (T2DM), insulin resistance and cardiovascular diseases (CVDs). In obesity, chronic metabolic stresses trigger adipose tissue inflammation and promote macrophage infiltration, resulting in aberrant secretion of bioactive peptides (known as adipokines). Our primary research interest is to investigate the role of adipokines in the pathogenesis of obesity-related insulin resistance, systemic inflammation, T2DM and vascular dysfunctions in animal models and human subjects. Our long-term goal is to develop adipokine-based diagnostic and therapeutic strategies for obesity-related cardio-metabolic complications.

Identification and functional characterization of adipokine netowork:

Using an integrated proteomics-based approach, we have identified multiple posttranslationally modified isoforms of adiponectin, and have demonstrated that hydroxylation and subsequent glycosylation of several lysine residues at the collagenous domain are obligatory for insulin-sensitizing effects of adiponectin by promoting the formation of high molecular weight oligomeric complexes (Wang Y, JBC, 2002, 2005, 2006; Biohcem. J, 2008; Xu A, JCI, 2003). We have also identified the circulating form of adipocyte fatty acid-binding protein (A-FABP) and lipocalin-2 as pro-inflammatory adipokines mediating toxic lipids-induced insulin resistance and vascular dysfunction (Xu A, Clin Chem: 2006; Circulation: 2007; Hui X, JBC:2010). More recently, we have demonstrated that fibroblast growth factor (FGF21), an anti-diabetic hormone traditionally thought to be produced from hepatocytes, is also secreted from adipose tissues (Zhang X, Diabetes, 2008 and Lin Z, Cell Metabolism, 2013). Furthermore, we found that adipose-derived FGF21 exerts its anti-diabetic activities by inducing adiponectin production (Fig 1). Currently, we are investigating the mechanisms by which FGF21 controls adiponectin production under physiological and pathological conditions.

Research photos Fig1. Adiponectin confers the metabolic of FGF21 in the liver and skeletal muscle

Signaling mechanisms underlying the insulin-sensitizing and vascular protective effects of adiponectin:

Adiponectin is one of the few adipokines with insulin-sensitizing and cardiovascular protective properties, but its mechanisms of actions remain poorly characterized. In 2007, We identified APPL1, an intracellular adaptor protein, as a key signaling molecule that bind to adiponectin receptors mediating adiponectin-induced activation of AMP-activated protein kinase (AMPK), thereby inducing eNOS activation and NO production in endothelial cells (Cheng KK, Diabetes, 2007). Our subsequent studies demonstrated that APPL1 is also a key component of insulin-evoked signaling cascade, by promoting membrane targeting and translocation of the protein kinase Akt (Cheng KK, Cell Metab. 2009; BJ, 2013). Furthermore, using APPL1 transgenic and knockout mice, we have found that APPL1 plays a central role in controlling vascular homeostasis as well as insulin secretion (Cheng KK, PNAS, 2012; Wang Y, Diabetes, 2011). 

Research photos Fig2. Multiple signaling pathways contribute to the vascular protective effects of adiponectin

Translational research: Adipokines-based assay development, clinical diagnosis and drug discovery:

Through the Antibody and Immunoassay Service (AIS, www.antibody.hku.hk), we have developed over 20 highly specific immunoassay kits for new adipokines and other biomarkers related to cardio-metabolic diseases. These assay kits are now being commercialized for basic and clinical research, clinical diagnosis and high throughput drug screening. We are working with several overseas and Mainland hospitals to conduct long-term prospective studies to validate the clinical values of our several adipokine assays for risk prediction and early diagnosis of cardiovascular complications of diabetes in different ethnic groups. In addition, we are now using these adipokines as biomarkers for high throughput screening of new compounds from medicinal herbs with anti-diabetic and vasculoprotective properties and for discovery of drug candidates for obesity-related medical complications by targeting the adipo-vascular axis