Obesity and Metabolic Disease Research Group

We focus on three core research areas.

Examining the role of neuropeptide Y family members in obesity and diabetes

Obesity is a global epidemic. It is associated with a high risk of several serious diseases, including type 2 diabetes, cardiovascular disease (CVD) and certain cancers. Obesity occurs when there is an imbalance between energy intake and energy expenditure. Understanding how energy balance is regulated under health and disease will facilitate the development of better therapeutics for obesity and its complications.

Neuropeptide Y (NPY) is a critical regulator, controlling both energy intake and energy expenditure. Activation of NPY at the hypothalamic arcuate nucleus (Arc) stimulates food intake and reduces energy expenditure. It is extensively expressed in the central nervous system (CNS) and the periphery. There are three ligands, or chemical messengers, in the NPY family: NPY, peptide YY (PYY) and pancreatic polypeptide (PP). These exert their actions via at least five G-protein-coupled receptors (GPCRs) – Y1, Y2, Y4, Y5 and y6 – which are differentially expressed in the CNS and peripheral tissues, including adipose tissue, pancreatic islets, blood vessels and bone.

Our group's primary research interest is to understand the physiological and molecular mechanisms that control energy and glucose homeostasis in health and disease, with a special emphasis on evaluating the critical actions of centrally and peripherally produced NPY family members in these processes. Using novel germline and conditional transgenic and knockout mouse models, along with cutting-edge molecular techniques (e.g. chemogenetics, optogenetics, TRAP, RNA-sequencing and lipidomics), we are investigating the phenotypic characterisations of energy balance and glucose homeostasis in mouse models and dissecting the associated molecular mechanisms and neuronal pathways. Our research focuses on adipose tissue thermogenesis and metabolism, insulin secretion in pancreatic islets, obesity and NPY-related CVDs (e.g. hypertension and atherosclerosis) and cancer.

Determining the crosstalk of metabolically active tissues

Maintaining energy and glucose homeostasis requires the coordination of different organs in the body. Dysregulation of this coordination under metabolic challenges contributes to the development of obesity and diabetes. We are examining the important interplay between adipose tissue and pancreatic islets, the cardiovascular system and bone. By using an array of in vivo, ex vivo and in vitro methods, we aim to discover the key molecules and pathways important in this control in health and disease. In addition to this, lifestyle modifications such as caloric restriction and exercise have shown tremendous benefits in weight loss. We are also interested in understanding how these lifestyle interventions modulate the interplay between these organs, with the aim of identifying novel molecules/mimetics for the treatment of obesity, diabetes and CVD.

Defining the contribution of noncaloric nutrients to energy balance

Salt (NaCl) is a noncaloric nutrient that plays a critical role in regulating fluid balance. Excessive salt consumption has been linked to hypertension and other CVDs. High sugar and high fat diets are usually high in salt content. However, little is known about how high salt intake influences the development of diet-induced obesity and diabetes. We are investigating the potential contribution of salt to energy and glucose balance, and defining the neuronal and peripheral pathways behind the salt-induced phenotypes.