The role of somatosensory innervation of adipose tissues

Abstract

Adipose tissues communicate with the central nervous system to maintain whole-body energy homeostasis. The mainstream view is that circulating hormones secreted by the fat convey the metabolic state to the brain, which integrates peripheral information and regulates adipocyte function through noradrenergic sympathetic output1. Moreover, somatosensory neurons of the dorsal root ganglia innervate adipose tissue2. However, the lack of genetic tools to selectively target these neurons has limited understanding of their physiological importance. Here we developed viral, genetic and imaging strategies to manipulate sensory nerves in an organ-specific manner in mice. This enabled us to visualize the entire axonal projection of dorsal root ganglia from the soma to subcutaneous adipocytes, establishing the anatomical underpinnings of adipose sensory innervation. Functionally, selective sensory ablation in adipose tissue enhanced the lipogenic and thermogenetic transcriptional programs, resulting in an enlarged fat pad, enrichment of beige adipocytes and elevated body temperature under thermoneutral conditions. The sensory-ablation-induced phenotypes required intact sympathetic function. We postulate that beige-fat-innervating sensory neurons modulate adipocyte function by acting as a brake on the sympathetic system. These results reveal an important role of the innervation by dorsal root ganglia of adipose tissues, and could enable future studies to examine the role of sensory innervation of disparate interoceptive systems.

Schwann cells contribute to demyelinating diabetic neuropathy and nerve terminal structures in white adipose tissue

“… 18 We also labeled sensory nerves for the sensory-specific neuropeptide calcitonin gene-related peptide (CGRP). Of note, recent findings reveal that up to 40% of adipose sensory nerves are TH+, 19 making it difficult to clearly delineate between sympathetic and sensory identity. In addition, this binary distinction between sensory and sympathetic may underrepresent the overall diversity of adipose nerves since sensory nerves can release a variety of neuropeptides, sympathetic nerves can co-release modulatory neuropeptides with norepinephrine, and non-peptidergic sensory fibers are only beginning to be described in scWAT.…”

“…Unexpectedly, we found that NANs are also labeled by the sensory marker CGRP ( Figure 5 E) which suggests that they may be innervated by the population of TH+ dorsal root ganglion neurons that comprise 40% of sensory innervation in scWAT. 19 This unfortunately provides little incite to their function as TH+ DRG neurons innervate numerous target organs and tissues and display distinct functional characteristics specific to the target. 27 Because of this, it is difficult to clearly define the function of NANs.…”

“… 49 Whereas these studies identified selected populations of myelinated sympathetic nerves, we observed a nearly complete overlap between TH and MBP within scWAT and found that the majority of TH+ nerve fibers are at least thinly myelinated in the mouse scWAT tissue environment. This observation may be partially explained by the recent discovery that over 40% of sensory nerves in scWAT are TH+, 19 highlighting the need for more in-depth characterization of adipose nerve heterogeneity and more specific sympathetic nerve markers.…”

The cold‐sensing ion channel TRPM8 regulates central and peripheral clockwork and the circadian oscillations of body temperature

“…Indeed, the absence of TRPM8 greatly impaired clockwork in these two metabolic tissues, which highlights TRPM8 sensory information as a major factor regulating liver and WAT circadian cycles. Our findings, coupled with the application of novel molecular tools to define and manipulate sensory innervation in an organ-specific manner, 59 will shed light on the relevance and the molecular signals of the communication between dorsal root ganglia (DRG) neurons and peripheral organs, like WAT and liver.…”

Targeting PI3K/AKT signaling pathway in obesity

“…Adipose tissue is a structurally heterogeneous endocrine organ that consists of fat cells (adipocytes) and their precursors (preadipocytes) [38], as well as fibroblasts, endothelial cells, vascular cells [10], resident immune cells (predominantly macrophages) [39], and neuronal cells [40]. These different cell types are essential for the physiological role of the adipose tissue, but they often interact in the pathophysiological complications of obesity.…”