Sympathetic innervation of the interscapular brown adipose tissue in mouse

François, Marie; Torres, Hayden; Huesing, Clara; Zhang, Rui; Saurage, Carson; Lee, Nathan; Qualls‐Creekmore, Emily; Yu, Sangho; Morrison, Christopher; Burk, David H.; Berthoud, Hans Rudolf; Münzberg, Heike

doi:10.1111/nyas.14119

Cited by 47 publications

(46 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Next, we looked for evidence of PRV labeling in DRG sensory neurons. In a similar study of interscapular brown adipose tissue-derived PRV labeling, we identified a low, but consistent PRV labeling in the DRG (Francois et al, 2019). In contrast to interscapular brown adipose tissue (iBAT)-related labeling (Francois et al, 2019;Münzberg et al, 2019), DRG ganglia showed only occasional PRV labeling with typically <5 neurons per ganglion and most often observed in DRG T11 and T12 in 46 and 30%, respectively, of all analyzed animals ( Figure 3, Table 2).…”

Section: Microscopy and Image Processingsupporting

confidence: 65%

“…In a similar study of interscapular brown adipose tissue-derived PRV labeling, we identified a low, but consistent PRV labeling in the DRG (Francois et al, 2019). In contrast to interscapular brown adipose tissue (iBAT)-related labeling (Francois et al, 2019;Münzberg et al, 2019), DRG ganglia showed only occasional PRV labeling with typically <5 neurons per ganglion and most often observed in DRG T11 and T12 in 46 and 30%, respectively, of all analyzed animals ( Figure 3, Table 2). We note that iWAT-derived PRV was not co-localized with TH-positive DRG neurons which lack authentic catecholaminergic functions (Kummer, Gibbins, Stefan, & Kapoor, 1990).…”

Section: Microscopy and Image Processingsupporting

confidence: 65%

“…In some cases we used TH:tomato mice to enhance visibility of fine nerves. Perfusion and immunohistochemistry were performed as previously described (Francois et al, 2019). Mice were deeply anesthetized with an overdose of isoflurane, followed by a transcardiac syringe perfusion with ice-cold physiological saline, then 10% neutral buffered formalin (Fisher, Passaic, NJ).…”

Section: Fluorescence-guided Dissection Of Tissuementioning

confidence: 99%

See 2 more Smart Citations

Sympathetic innervation of inguinal white adipose tissue in the mouse

Huesing

Qualls‐Creekmore

Lee

et al. 2020

J of Comparative Neurology

Self Cite

View full text Add to dashboard Cite

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. K E Y W O R D S iDISCO, imaging, pseudorabies virus, sympathetic chain ganglia, tissue clearing, transsynaptic retrograde tracing 1 | INTRODUCTION Historically, white adipose tissue (WAT) was largely considered a storage depot for excess energy (Steiner & Cahill, 1964). However, 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

show abstract

Section: Microscopy and Image Processingsupporting

confidence: 65%

Section: Microscopy and Image Processingsupporting

confidence: 65%

Section: Fluorescence-guided Dissection Of Tissuementioning

confidence: 99%

See 1 more Smart Citation

Sympathetic innervation of inguinal white adipose tissue in the mouse

Huesing

Qualls‐Creekmore

Lee

et al. 2020

J of Comparative Neurology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Adaptive thermogenesis by BAT is triggered by release of NE from postganglionic sympathetic neurons (69), and NE levels in BAT under steady-state conditions have historically been used as a direct index of SNS innervation of BAT (70). We did not observe any signi cant effects of DDT or DDE on NE or DHPG levels in BAT from 4-month old female mice.…”

Section: Discussionmentioning

confidence: 99%

Developmental Exposure to DDT or DDE Alters Sympathetic Innervation of Brown Adipose in Adult Female Mice

vonderEmbse

Elmore

Jackson

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Exposure to the bioaccumulative pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) has been associated with increased risk of insulin resistance and obesity in humans and experimental animals. These effects appear to be mediated by reduced brown adipose tissue (BAT) thermogenesis, which is regulated by the sympathetic nervous system. Although the neurotoxicity of DDT is well-established, whether DDT alters sympathetic innervation of BAT is unknown. We hypothesized that perinatal exposure to DDT or DDE promotes thermogenic dysfunction by interfering with sympathetic regulation of BAT thermogenesis. Methods: Pregnant C57BL/6J mice were exposed by oral gavage to environmentally relevant concentrations of DDT (1.7 mg/kg) or DDE (1.31 mg/kg) from gestational day 11.5 to postnatal day 5, and longitudinal body temperature was recorded in male and female offspring. At 4 months of age, metabolic parameters were measured in female offspring via indirect calorimetry with or without the β3 adrenergic receptor agonist, CL 316,243. Immunohistochemical and neurochemical analyses of sympathetic neurons innervating BAT were evaluated.Results: We observed persistent thermogenic impairment in adult female, but not male, mice perinatally exposed to DDT or DDE. Perinatal DDT exposure significantly impaired metabolism in adult female mice, an effect rescued by treatment with CL 316,243 immediately prior to calorimetry experiments. Neither DDT nor DDE significantly altered BAT morphology or the concentrations of norepinephrine and its metabolite DHPG in the BAT of DDT-exposed mice. However, quantitative immunohistochemistry revealed a 20% decrease in sympathetic axons innervating BAT in adult female mice perinatally exposed to DDT, but not DDE, and 48% and 43% fewer synapses in stellate ganglia of mice exposed to either DDT or DDE, respectively, compared to control. Conclusions: These data demonstrate that perinatal DDT and DDE exposure impairs thermogenesis by interfering with patterns of connectivity in sympathetic circuits that regulate BAT.

show abstract

“…BAT nerves were later comprehensively investigated by the Bartness research group [3]. Energy expending BAT was the first adipose tissue to be identified as being highly innervated due to its important role in thermogenesis [4], which requires significant sympathetic nervous system (SNS) input and release of norepinephrine [2, 5, 6]. Sensory innervation has also been documented in BAT, particularly around vasculature, and has been proposed to play a role in lipolysis [7].…”

Section: Introductionmentioning

confidence: 99%

Visualization and Analysis of Whole Depot Adipose Tissue Neural Innervation

Willows

Blaszkiewicz

Lamore

et al. 2019

Preprint

View full text Add to dashboard Cite

53Adipose tissue requires neural innervation in order to regulate important metabolic functions. 54Though seminal work on adipose denervation has underscored the importance of adipose-nerve 55 interactions in both white (energy storing) and brown (energy expending) adipose tissues, much 56 remains a mystery. This is due, in part, to the inability to effectively visualize the various nerve 57 subtypes residing within these tissues and to gain a comprehensive quantitation of neurite 58 density in an entire depot. With the recent surge of advanced imaging techniques such as light 59 sheet microscopy and optical clearing procedures, adipose tissue imaging has been 60 reinvigorated with a focus on three-dimensional analysis of tissue innervation. However, 61 clearing techniques are time consuming, often require solvents caustic to objective lenses, alter 62 tissue morphology, and greatly reduce fluorophore lifespan. Not only are current methods of 63 imaging wholemount adipose tissues inconvenient, but often attempts to quantify neurite density 64 across physiological or pathophysiological conditions have been limited to representative 65 section sampling. We have developed a new method of adipose tissue neurite imaging and 66 quantitation that is faster than current clearing-based methods, does not require caustic 67 chemicals, and leaves the tissue fully intact. Maintenance of a fully intact depot allowed for tiling 68 z-stacks and producing maximum intensity projections of the entire adipose depot, which were 69 then used to quantify neurite density across the tissue. With this processing method we were 70 able to characterize the nerves, nerve-subtypes, and neurovascular interactions within the 71 inguinal subcutaneous white adipose tissue in mice using up to five fluorescent channels at high 72 resolution. We also utilized second harmonic generation, which provides label-free imaging, to 73 investigate collagen fiber abundance in adipose of obese mice. 74 75 76 77 78 79 80 81 82 83 84 85 86 87 Introduction: 88Historically overlooked as a location of diverse peripheral innervation [1], the adipose organ 89 was most prominently inspected for innervation in the mid 1960's when sympathetic nerve fibers 90 were visualized within brown adipose tissue (BAT) [2]. BAT nerves were later comprehensively 91 investigated by T.J. Bartness [3]. Energy expending BAT was the first adipose tissue to be 92 identified as being highly innervated due to its important role in thermogenesis [4], which 93 requires significant sympathetic input [2, 5, 6]. Sensory innervation has also been documented 94 in BAT, particularly around vasculature, and has been proposed to play a role in lipolysis [7]. 95More recently white adipose tissue (WAT), associated more with energy storage, was 96 demonstrated to be highly innervated by sympathetic [8, 9] and sensory nerves [5, 10], but not 97 parasympathetic [11] nerves. 98In order to visualize adipose innervation, it had been common practice to slice adipose 99 tissue into 7um-10um thick sections and...

show abstract

Sympathetic innervation of the interscapular brown adipose tissue in mouse

Cited by 47 publications

References 53 publications

Sympathetic innervation of inguinal white adipose tissue in the mouse

Sympathetic innervation of inguinal white adipose tissue in the mouse

Developmental Exposure to DDT or DDE Alters Sympathetic Innervation of Brown Adipose in Adult Female Mice

Visualization and Analysis of Whole Depot Adipose Tissue Neural Innervation

Contact Info

Product

Resources

About