Molecular Mechanisms of Adipose Cell Fate Determination
Energy balance is the biological homeostasis of energy in living organisms, which means energy intake from food (protein, carbohydrate and fat) equals energy expenditure (basal metabolism, physical activity, and adaptive thermogenesis). When energy intake exceeds energy expenditure, excess energy will be stored as fat in adipose and other metabolic tissues, eventually leading to obesity and further development into type II diabetes. Circulating hormones play critical roles to coordinate crosstalk within different metabolic tissues to regulate energy balance dynamically and precisely.
Fasting hormones, such as glucagon and catecholamines, utilize the cAMP-PKA signaling pathway to regulate glucose and lipid metabolism during fasting conditions. Elevations of cAMP in cells activate PKA, which in turn phosphorylates cAMP-response element binding protein (CREB) to induce gene expression. In addition, PKA can phosphorylate and inhibit Salt-inducible kinases (SIKs), members of AMPK-related kinase family. SIKs can modulate energy metabolism through phosphorylating CREB regulated transcription coactivators (CRTCs) and class IIa histone deacetylases (HDACs) respectively, revealing that SIKs govern two downstream branches of cAMP signaling to regulate gene expression and diverse metabolic programs.
Currently, we are taking integrated approaches to understand how SIKs orchestrate energy metabolism in various tissues and how hormones regulate SIKs’ activities.