The regulation of adipose-derived MIF: A novel secretory function of preadipocytes mediated by PAR2

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Adipose tissue is commonly considered as an organ system responsible for energy storage, temperature regulation and wound healing, yet it is also an important endocrine organ which secrets hormones and inflammatory factors that mediate metabolic process in mammals. The molecular mechanisms in regulating the secretory function of adipose tissue are largely unknown and revealing these mechanisms will have important implications for animal physiology and biochemistry. Thus, our long-term goal is to elucidate how adipose tissue orchestrates whole-body metabolism as an endocrine organ. Our short-term goal for the next 5 years is to investigate the signaling cascades involved in the regulation of synthesis and release of an adipose derived protein, macrophage migration inhibitory factor (MIF). MIF is an evolutionarily conserved protein which is composed of three identical monomers and possesses unique tautomerase enzymatic activity to catalyze the conversion of D-dopachrome into 5,6-dihydroxyindole-2-carboxylic acid in non-mammalians. In mammals, MIF was first discovered in immune cells (macrophage/monocyte) and it was released from pre-formed storage pools in response to stimulation. MIF is also widely expressed in metabolically active tissues including adipose tissue, heart and liver; among these, the adipose tissue is the major resource of plasma MIF. MIF released from adipose tissue attenuates insulin signaling in peripheral tissues (adipose, skeletal muscle and liver) and thus it plays a key role in energy metabolism. However, it remains unclear how the expression and release of MIF is regulated in adipose tissue. Thus, our current project will employ a comprehensive strategy involving both in vitro and in vivo studies, utilizing various techniques in molecular and cellular biology including qPCR, western blot and immunohistochemistry etc.In this study, our aims are to:(1) Examine MIF expression and release from adipose tissue in response to adipose differentiation. (2) Define the role of PAR2 in mediating preadipocytes and MIF expression in adipose tissue. (3) Evaluate preadipocyte pool and MIF expression in response to fatty acid stimulation. We believe identifying the mechanisms in mediating the expression and release of MIF in adipose tissue will be an important effort to reveal the endocrine function of adipose tissue and discover how adipose tissue orchestrates whole-body metabolism. Our findings might have a long-term impact in academic studies of animal biology and physiology.HQP including graduate students and honors program undergraduate students will be involved in this project. The students will be widely exposed to various concepts and experimental techniques of natural sciences. In addition, graduate students will develop their own research interests based on the current proposed mechanisms.