Sympathetic nerve-adipocyte interactions in response to acute stress

Abstract

Psychological stress predisposes our body to several disorders. Understanding the cellular and molecular mechanisms involved in the physiological responses to psychological stress is essential for the success of therapeutic applications. New studies show, by using in vivo inducible Cre/loxP-mediated approaches in combination with pharmacological blockage, that sympathetic nerves, activated by psychological stress, induce brown adipocytes to produce IL-6. Strikingly, this cytokine promotes gluconeogenesis in hepatocytes, that results in the decline of tolerance to inflammatory organ damage. The comprehension arising from this research will be crucial for the handling of many inflammatory diseases. Here, we review recent advances in our comprehension of the sympathetic nerve-adipocyte axis in the tissue microenvironment.

Keywords: Adipocytes; Hepatocytes; IL-6; Microenvironment; Sympathetic nerves.

Fig. 1

Sympathetic nerve-adipocyte-hepatocyte axis dictates physiologic response to acute psychological stress. Using state-of-the-art technologies, Qing and colleagues demonstrated that, after acute psychological stress, sympathetic nerves induce brown adipocytes to increase circulatory IL-6 levels. IL-6 signals to hepatocytes to increase glucose production via gluconeogenesis leading to hyperglycemia. This results in a decline in the organism tolerance to inflammatory organ damage [14]

Fig. 2

Schematic illustration summarizing the possible role of sympathetic nerves on multiple inflammatory diseases via IL-6. After acute psychological stress, sympathetic nerves induce the increase in the levels of IL-6 which leads to other pathophysiologic effects [14]. IL-6 plays important roles in the pathogenesis of multiple disorders. Future studies will reveal whether sympathetic nerves are also responsible for IL-6 production in these pathological conditions

Fig. 3

Possible role of sympathetic nerves and brown adipocytes in COVID-19 pathogenesis. High levels of circulating IL-6 are associated with worse outcomes in COVID-19 patients. It will be interesting to examine whether SARS-Cov-2 virus activates the sympathetic nerve-brown adipocyte axis to produce IL-6. During the pandemic, patients also suffer with social isolation what leads to acute psychological stress, with the possible involvement of sympathetic nerves in the production of IL-6

Fig. 4

Potential new mechanism of sympathetic nerve role within the tumor microenvironment. Different nerve fibers, including sympathetic innervations, infiltrate the tumors, and affect their development. The detailed molecular mechanisms by which sympathetic nerves influence cancer progression remain incompletely understood. Future studies should examine whether sympathetic nerves also act within tumors via IL-6 derived from intra-tumoral adipocytes