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Development of new anti-obese strategies by conversion of white fat to brown fat


Department of Medicine

Applications accepted all year round Funded PhD Project (Students Worldwide)

About the Project

In contrast to white adipose tissue (WAT) that stores energy, brown adipose tissue (BAT) is specialized for energy dissipation and considered as a potential weapon to combat obesity by uncoupling mitochondrial respiratory chain and ATP synthesis. Recently, the ‘inducible’ brown adipocytes, denoted as ‘beige’ cells, were found scattering within the WAT. Animal-based studies have shown that functional beige or brown adipocytes possess multiple metabolic benefits independent of its adiposity-reducing effect, including insulin sensitizing, lipid lowering, anti-inflammatory and anti-atherosclerotic effects.

In adult human, a significant amount of active brown/beige adipose tissue has been detected by positron emission tomography (PET) and its amount/activity is inversely related to ageing, obesity and a cluster of cardio-metabolic diseases. Moreover, activation of brown/beige adipocytes in human by cold acclimation confers protection against a series of metabolic disorders. Notably, beiging of WAT requires participation of immune responses. We have discovered that adipokines, including adiponectin and FGF21, contribute to cold-induced beige cell biogenesis by fostering the type 2 immune responses in WAT, which involves sequential activation of IL-C2 cells, eosinophils and M2 macrophages. However, whether and how other immune cells are involved in this process is unknown.

Compared to the RNA-sequencing-based bulk analysis, single cell sequencing examines the sequence information from individual cells, facilitating a higher resolution of cellular differences and a better understanding of the function of an individual cell in the context of its microenvironment. Therefore, in order to gain a further insight into the immunological events underlying brown remodeling of WAT, we will perform single cell sequencing analysis in mouse WAT before and after cold-induced browning. The novel immune cells involved will be identified. Cell and animal-based studies will be carried out to further elucidate the molecular mechanisms whereby the immune cell integrates into the immune-metabolism network during adipose browning. The findings will also be verified in human adipose biopsies so as to explore the clinical relevance of the study. Implementation of the study will identify novel factors/pathways that engage WAT browning, and thereby provide new targets for treatment of obesity and metabolic complications.

Supervisor

Professor Aimin Xu has been focusing on both basic and translational research on obesity/diabetes-related disorders. He is leading the State Key Laboratory of Pharmaceutical Biotechnology, which is at the forefront of innovation and discovery in the field of molecular metabolism, with a focus on hormones and biomarkers (www.sklpb.hku.hk). Professor Xu has made significant contributions to discovery and functional characterization of several adipokines and hormones including adiponectin, fibroblast growth factor 21 (FGF21), adipocyte-fatty acid binding protein (A-FABP) and lipocalin-2. For recent publications from his group, please visit https://scholar.google.com/citations?user=vyPfQmIAAAAJ&hl=en

Faculty information, funding opportunities and application deadlines: https://www.findaphd.com/phds/program/biomedical-research-hku-li-ka-shing-faculty-of-medicine/?i586p4119

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