p38 mitogen-activated protein kinase plays a critical role in the control of energy metabolism and development of cardiovascular diseases.

p38 mitogen-activated protein kinase (p38) is a member of MAP kinase family. Its wide-spectrum roles in the control of energy metabolism have been indicated in numerous studies. p38 participates in the energy metabolism in all major tissues/organs involved in the control of energy metabolism, including adipose tissue, skeletal muscles, islet cells, and liver. In white adipose tissue, p38 plays an important role in adipose differentiation and glucose uptake although it is still inconclusive whether this role of p38 is stimulatory or inhibitory. The stimulatory role of p38 in transcription of the uncoupling protein 1 (UCP1) gene in brown adipose tissue is relatively clear. A fundamental role for p38 in the differentiation of skeletal muscles and mitochondrial biogenesis in skeletal muscles is rather definitive although the role of p38 in glucose uptake of skeletal muscles remains controversial. In islet cells, p38 appears to be involved in beta-cell apoptosis. p38 has been indicated in the control of preproinsulin gene transcription, but remains controversial. However, it seems clear that p38 does not play a significant role in insulin secretion. In the liver, p38 plays a central role in hepatic glucose and lipid metabolism. Activation of p38 participates in the processes to increase blood glucose levels through reducing glycogen synthesis and increasing hepatic gluconeogenesis. p38 appears to prevent fat storage by inhibiting hepatic lipogenesis and promoting fatty acid oxidation in the liver. Additionally, p38 may play a critical role in cholesterol metabolism by regulating expression of the LDLR gene and bile metabolism. p38 does not only participate in various physiological and pathophysiological processes in cardiomyocytes, but also is heavily involved in the development of atherosclerotic lessions through its influences on monocytes/macrophages, vascular endothelial cells, and vascular smooth muscle cells.