2020-04-22T10:06:13+08:002019-09-18|Seminars and Workshops|


Talk title  Targeting MT1-MMP: Therapeutic Opportunities in Obesity, Type 2 Diabetes and Other Associated Diseases
Speaker Prof. Hoi Leong Xavier WONG
Research Assistant Professor
School of Chinese Medicine, Hong Kong Baptist University
Date & Time 17 Sep 2019 (Tue)
Venue Room G004, E12 Building (University of Macau)
Abstract Obesity and diabetes are major causes of morbidity and mortality. Obesity is known to be the main risk factor for various non-communicable diseases, in particular type 2 diabetes. There is an ongoing need to identify non-invasive therapeutic approaches for the management of obese patients with type 2 diabetes to achieve their glycemic and weight loss goals.

Recently, mutations in MT1-MMP (MMP14), a membrane bound metalloproteinase responsible for extracellular matrix remodeling and pericellular proteolysis, have been associated with human obese and diabetic traits. In this talk, the role of MT1-MMP in energy and glucose homeostasis and the molecular mechanism by which MT1-MMP regulates body weight and insulin sensitivity will be discussed. Here we show that MT1-MMP contributes to the development of metabolic disorders through increasing energy intake and impairing insulin sensitivity. Obesity increases the expression of MT1-MMP systematically. Ectopic expression of MT1-MMP in mouse liver induces insulin resistance in regular chow-fed mice. Conversely, inhibition of MT1-MMP activities by either genetic knockout or pharmacological approaches leads to the weight loss along with improved insulin sensitivity in both young mice with high-fat-diet induced obesity and aged mice fed with regular chow diet. Mechanistically, we found that MT1-MMP is a suppressor for GDF15-GFRAL signaling pathway, a newly identified central nervous system circuit that regulates metabolism and food intake in response to stress. In addition, MT1-MMP also impairs insulin signaling in the control of peripheral insulin sensitivity and glucose metabolism. These results indicate that MT1-MMP constitutes an important modulator of insulin sensitivity and energy homeostasis. Thus, targeting MT1-MMP represents potential therapeutics for the management of obesity and type 2 diabetes, two diseases with a need for combined treatment strategies.