4. Development of novel therapeutics for metabolic diseases
1) Activation of browning of white adipose tissue
♦ Obesity develops when energy intake exceeds energy expenditure. Excessive energy in our body leads to increased adipose tissue mass and to ectopic lipid deposition, insulin resistance, type-2 diabetes, cardiovascular diseases and certain cancers. Over the last 20 years, adipose tissue has emerged as a central regulator of energy homeostasis and metabolic disorders. Its well-known function is energy store as a fat, but it also expends energy by producing heat, referred to non-shivering thermogenesis (Cell 2012, BMB Reports 2014, Diabetologia 2015).
There are two types of adipose tissue: white adipose tissue (WAT)-energy storing fat and brown adipose tissue (BAT)-energy burning fat. Recent studies identify a new type of thermogenic adipose tissue, “beige” adipose tissue. Classical brown adipocytes are found in the dedicated BAT depots of rodents, such as in the interscapular, perirenal, and periaortic regions and constitutively highly express thermogenic genes, whereas beige adipocytes are dramatically induced in response to certain external cues, such as chronic cold exposure, exercise, and long-term treatment with PPARγ agonists in subcutaneous white adipose tissue of rodents. Although they originate from distinct cellular lineages, they share many biochemical characteristics, including enriched mitochondria, multilocular lipid droplets, and expression of UCP1. As many studies demonstrate that the activation of brown and beige adipocytes could reduce the incidence of metabolic disease, including obesity in both mice and humans. Thus, understanding the regulatory mechanism of brown and beige adipocyte biology may provide a variety of promising therapeutic targets for metabolic disease (Diabetes 2016).
Our lab is trying to identify novel target genes and pathways to develop or activate brown/beige adipocytes using global gene expression analysis and MS-based proteomic analysis, and characterize the molecular mechanism of target molecules.