Neural Innervation of Adipose Tissue: Current Understanding and Future Perspective

Adipose tissue plays a pivotal role in metabolic homeostasis regulation. It is predominantly innervated by sympathetic efferent and sensory afferent nerves, forming a bidirectional communication network. Although the sympathetic innervation of adipose tissue has been extensively studied before, several novel insights have been provided recently. In contrast, the functional significance of sensory innervation in adipose tissue remains underexplored.

This review summarized recent advances between adipocytes and nerve innervation in metabolic regulation. Furthermore, we demonstrated the interplay between immune cells and nerve fibers within adipose tissue, as well as the crosstalk between sympathetic efferent and sensory afferent nerves in metabolic processes. Our review suggests targeting zinc/Mg supplementation, the calsyntenin-3β-S100b, and the leptin-brain-derived neurotrophic factor axis have become promising therapies to treat obesity and other metabolic diseases. Of note, the sympathetic innervation is vital for adipose adaptation to long-term metabolic challenges with different energy demands, and it remains to be explored whether sensory nerves have similar capacity upon different energy challenges, particularly in different strains of rodents as well as across species.

The crosstalk in adipose tissue microenvironment plays an essential role in metabolic homeostasis regulation. The functions and mechanisms of sensory afferent nerves and the dynamic interplay between sympathetic efferent and sensory afferent nerves in adipose tissue represent a critical frontier for more detailed research.