The relative degree of adipose tissue responsiveness to catecholamines reflects the balance of multiple forces, each of which are shaped by a combination of genetic and environmental factors. On the genetic side are the developmentally programmed patterns and density of innervation into various adipose depots, and the amounts and types of the specific adrenergic receptors (ARs) and their metabolic targets that are expressed on the adipocytes within different depots. Within the latter aspect is whether the receptors are stimulatory (βARs) or inhibitory (αARs) for lipolysis, their coupling efficiency to the downstream signaling molecules, and the relative kinetic activity of those regulated enzymes, scaffolding proteins and transcription factors. Finally, there is the genetic profile that predisposes preadipocytes toward the progression of the brown versus white adipocyte phenotype. On the environmental side, diet contributes to the relative degree of adipose tissue response to catecholamines by altering the hormonal and metabolic signals that control important adipocyte genes. These include the ARs themselves, the kinase pathways ARs regulate, and hence also the ability to determine decisions about fat storage versus thermogenesis.
With our increased understanding of the SNS circuitry from the CNS to adipose tissue and the newer appreciation of signaling pathways that are activated in adipocytes by catecholamines, science is positioned in the future to better define the molecular and genetic regulatory points that determine adipose tissue sensitivity to dietary and other environmental forces, and to establish the underlying basis for the molecular decisions that drive a cell to become a white or brown fat cell. Such new insights that will be gained as a result will hopefully generate new therapeutic targets and approaches against the obesity epidemic in our midst.