Potential Therapeutic Role and Mechanism of Mesencephalic Astrocyte-Derived Neurotrophic Factor in Metabolic Disease

Abstract

Metabolic disease is a global epidemic and gradually became a serious public health problem, which comprised a few similar metabolic disorders such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. Metabolic diseases are characterized by the accumulation of abundant nutrients, subsequently induce glucolipotoxicity, intracellular stress, inflammation, and ultimately cell damage. Endoplasmic Reticulum stress (ER stress) exerts an important role in the pathogenesis of metabolic disease. ER stress could induce the inflammation and insulin resistance in adipocytes and hepatocytes, increase the apoptosis of pancreatic β cells and hepatocytes, and promote the gluconeogenesis and fatty acids synthesis. Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) and Cerebral Dopamine Neurotrophic Factor (CDNF) are the newly discovered Neurotrophic Factors (NTFs), which are firstly discovered for the neuroprotective functions. Both MANF and CDNF have a similar structure, but emerging evidence showed the prominent metabolic effect of MANF. MANF is also a secreted protein, located in the endoplasmic reticulum and ER stress would induce its expression and secretion. MANF is involved in food intake and the proliferation and survival of pancreatic β cells. Furthermore, MANF can protect hepatocyte against metabolic stress damage. Regards that the potential role of MANF in metabolic disease and ER stress, in this review, we summarized the molecular structure, physiological function and potential therapeutic role and mechanism of MANF in metabolic diseases.