Abstract
Adipose tissue plays an important role in metabolic homeostasis and its prominent role as endocrine organ is now well recognized. Adipose tissue is controlled via the sympathetic nervous system (SNS). New viral, molecular‐genetic tools will soon allow a more detailed study of adipose tissue innervation in metabolic function, yet, the precise anatomical extent of preganglionic and postganglionic inputs to the inguinal white adipose tissue (iWAT) is limited. Furthermore, several viral, molecular‐genetic tools will require the use of cre/loxP mouse models, while the available studies on sympathetic iWAT innervation were established in larger species. In this study, we generated a detailed map for the sympathetic innervation of iWAT in male and female mice. We adapted iDISCO tissue clearing to process large, whole‐body specimens for an unprecedented view of the natural abdominal SNS. Combined with pseudorabies virus retrograde tracing from the iWAT, we defined the preganglionic and postganglionic sympathetic input to iWAT. We used fluorescence‐guided anatomical dissections of sympathetic nerves in reporter mice to further clarify that postganglionic axons connect to iWAT via lateral cutaneous rami (dorsolumbar iWAT portion) and the lumbar plexus (inguinal iWAT portion). Importantly, these rami carry axons that branch to iWAT, as well as axons that travel further to innervate the skin and vasculature, and their functional impact will require consideration in denervation studies. Our study may serve as a comprehensive map for future experiments that employ virally driven neuromodulation techniques to predict anatomy‐based viral labeling.
Highlights
White adipose tissue (WAT) was largely considered a storage depot for excess energy (Steiner & Cahill, 1964)
Our study aimed to provide a comprehensive evaluation of preganglionic and postganglionic sympathetic inputs to inguinal white adipose tissue (iWAT) in male and female mice, which allows the reconstruction of anatomical ganglia levels from their undisturbed location in whole body images
Recent reports have suggested that iWAT in mice may receive significant innervation by the celiac complex (Cao, Wang, & Zeng, 2018; FIGURE 7 Sympathetic chain ganglia T11–T13 provide sympathetic innervation to dorsolumbar white adipose tissue (WAT) via lateral cutaneous nerves. (a) Distribution of lateral cutaneous rami of intercostal nerves T11–T13 to dorsolateral iWAT as seen under the stereomicroscope (0.5× objective)
Summary
White adipose tissue (WAT) was largely considered a storage depot for excess energy (Steiner & Cahill, 1964). Given the increasing number of obese individuals plagued with metabolic syndrome, and the associated risk for life-threatening comorbidities like Type 2 diabetes, cancer, and cardiovascular disease (Eyre et al, 2004), intense research over the last decades has highlighted a. Just as excess adipose tissue poses clear health risks, the lack of adipose tissue, lipodystrophy, leads to severe metabolic dysfunction, like liver steatosis and insulin resistance (Petersen et al, 2002). Since the sympathetic nervous system (SNS) plays a critical role for the induction of lipolysis in adipocytes (Bartness, Shrestha, Vaughan, Schwartz, & Song, 2010; Leboeuf, Flinn, & Cahill, 1959; Weiss & Maickel, 1968), it is a good candidate for obesity interventions
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