Molecular pathways linking adipose innervation to insulin action in obesity and diabetes mellitus

Abstract

Adipose tissue is comprised of adipocytes and many other cell types which engage in dynamic crosstalk in a highly innervated and vascularized tissue matrix. Although studied for decades, it is only recently appreciated that extensive arbors of sensory and sympathetic nerve fibers play a dominant role in regulation of adipose functions. Here we summarize recent literature suggesting adipocytes signal to local sensory nerve fibers in response to perturbations in lipolysis and lipogenesis. Such adipocyte signaling to the central nervous system (CNS) causes sympathetic output to distant adipose depots and potentially other metabolic tissues to regulate systemic glucose homeostasis. Recently identified paracrine factors that mediate such adipocyte-neuron crosstalk are reviewed. Similarly, immune cells and endothelial cells within adipose tissue communicate with local nerve fibers to modulate neurotransmitter tone, blood flow, adipocyte differentiation and energy expenditure, including adipose “browning” to produce heat. This understudied field of “neurometabolism” related to adipose tissue biology has great potential to reveal new mechanistic insights and potential therapeutic strategies for obesity and type 2 diabetes.