Our view of how adipose tissue metabolism is regulated recently experienced a change in focus and breadth, meaning that some of the key controlling factors were not fully in the picture. The catecholamines of the sympathetic nervous system are well-known activators of β-adrenergic receptors in adipocytes to increase lipolysis. They also drive energy expenditure in brown adipose tissue and, importantly, the "browning" of cells in white adipose depots. However, this is clearly not the whole story. In earlier work, we established a pathway from β-adrenergic receptors to p38 MAP kinase to drive the transcription of brown adipocyte genes and respiratory uncoupling. Now we recently discovered that cardiac natriuretic peptides (NPs) stimulate a similar "browning" of human and mouse adipocytes. NPs activate the guanylyl cyclase coupled NP receptor A and activation of protein kinase G. Importantly, this pathway also depends upon p38 MAPK. These two pathways work together, additively increasing expression of brown adipocyte marker genes, as well as reflexively controlling each other's components. We discuss these findings and how the control of body fat by these cardiac hormones, in conjunction with the sympathetic nervous system, has implications for obesity as well as cardiovascular disease, including hypertension and heart failure.
Keywords: brown adipocyte; cyclic nucleotides; gene expression; thermogenesis; uncoupling.