JAK/STAT – Emerging Players in Metabolism

The JAK/STAT signaling pathway serves as an important downstream mediator for a variety of cytokines, hormones, and growth factors. Emerging data show that this pathway is dysregulated in metabolic diseases including obesity and type 2 diabetes. With the use of tissue-specific knockout mice, JAK/STAT signaling in the peripheral metabolic organs has been shown to regulate a multitude of metabolic processes including, but not limited to, glucose tolerance, insulin sensitivity, energy expenditure, and adiposity. JAK/STAT signaling within immune cells crucially regulates inflammation that is associated with metabolic abnormalities including insulin resistance and obesity. The JAK/STAT signaling pathway is a promising therapeutic target for the treatment of obesity, metabolic syndrome, and diabetes. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is crucial for transducing signals from a variety of metabolically relevant hormones and cytokines including growth hormone, leptin, erythropoietin, IL4, IL6 and IFNγ. A growing body of evidence suggests that this pathway is dysregulated in the context of obesity and metabolic disease. Recent development of animal models has been instrumental in identifying the role of JAK/STAT signaling in the peripheral metabolic organs including adipose, liver, muscle, pancreas, and the immune system. In this review we summarize current knowledge about the function of JAK/STAT proteins in the regulation of metabolism, and highlight new potential therapeutic targets for the treatment of obesity and diabetes. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is crucial for transducing signals from a variety of metabolically relevant hormones and cytokines including growth hormone, leptin, erythropoietin, IL4, IL6 and IFNγ. A growing body of evidence suggests that this pathway is dysregulated in the context of obesity and metabolic disease. Recent development of animal models has been instrumental in identifying the role of JAK/STAT signaling in the peripheral metabolic organs including adipose, liver, muscle, pancreas, and the immune system. In this review we summarize current knowledge about the function of JAK/STAT proteins in the regulation of metabolism, and highlight new potential therapeutic targets for the treatment of obesity and diabetes. exocrine cells of the pancreas which produce enzymes that assist in the digestion of food. a hormone secreted by adipose tissue that regulates energy homeostasis. a carrier protein for fatty acids that is expressed primarily in adipocytes and macrophages. a type of adipose tissue that functions to convert chemical energy into heat. a cell within the pancreatic islet that produces, stores, and secretes the hormone insulin. a protein that promotes neurotransmitter synthesis and neurite outgrowth. a mitogenic factor for cell growth, proliferation, and differentiation. a hormone produced by the kidney that promotes the formation of red blood cells by the bone marrow. impaired ability to properly dispose glucose, leading to elevated levels in circulation. a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates. a hormone that stimulates cell growth, proliferation and regeneration. a hormone with a similar structure to insulin that functions in growth, development, and metabolism. a pathological condition in which cells fail to respond physiologically to insulin. a cytokine involved in the immune response and inflammation. a cytokine involved in the immune response and inflammation. a hormone predominantly made by adipose tissue that regulates energy balance. a cluster of conditions that increase the risk of cardiovascular disease including central abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low high-density lipoprotein (HDL) levels. a type of chronic leukemia in which extensive scarring in the bone marrow disrupts normal production of blood cells. Activating JAK2 mutations are found in this condition. a strain of mice that develop spontaneous autoimmune pancreatic β-cell destruction that is used as a model of type 1 diabetes. a transcription factor necessary for pancreatic development. a group of transcription factors that regulate genes important for development and metabolism. a hormone secreted by the pituitary gland that promotes lactation. DNA sequence that regulates the expression of insulin in rats and mice. intracellular transcription factors that are primarily activated by membrane receptor-associated Janus kinases (JAKs). the abnormal retention of lipids within a cell. a type of immune cell that plays a role in the adaptive immune system. a transport protein, synthesized by the liver, that carries the thyroid hormone thyroxine and retinol-binding protein. a mitochondrial inner membrane protein that is responsible for converting energy to heat instead of ATP. the major site of energy storage in the form of fat, contributes to endocrine regulation of energy balance.