Characterization of the central neural projections to brown, white, and beige adipose tissue

Abstract

The functional recruitment of classic brown adipose tissue (BAT) and inducible brown-like or beige fat is, to a large extent, dependent on intact sympathetic neural input. Whereas the central neural circuits directed specifically to BAT or white adipose tissue (WAT) are well established, there is only a developing insight into the nature of neural inputs common to both fat types. Moreover, there is no clear view of the specific central and peripheral innervation of the browned component of WAT: beige fat. The objective of the present study is to examine the neural input to both BAT and WAT in the same animal and, by exposing different cohorts of rats to either thermoneutral or cold conditions, define changes in central neural organization that will ensure that beige fat is appropriately recruited and modulated after browning of inguinal WAT (iWAT). At thermoneutrality, injection of the neurotropic (pseudorabies) viruses into BAT and WAT demonstrates that there are dedicated axonal projections, as well as collateral axonal branches of command neurons projecting to both types of fat. After cold exposure, central neural circuits directed to iWAT showed evidence of reorganization with a greater representation of command neurons projecting to both brown and beiged WAT in hypothalamic (paraventricular nucleus and lateral hypothalamus) and brainstem (raphe pallidus and locus coeruleus) sites. This shift was driven by a greater number of supraspinal neurons projecting to iWAT under cold conditions. These data provide evidence for a reorganization of the nervous system at the level of neural connectivity following browning of WAT.-Wiedmann, N. M., Stefanidis, A., Oldfield, B. J. Characterization of the central neural projections to brown, white, and beige adipose tissue.

Convergent neuronal projections from paraventricular nucleus, parabrachial nucleus, and brainstem onto gastrocnemius muscle, white and brown adipose tissue in male rats

“…We used isogenic strains of PRV that have a distinct fluorescent reporter of either GFP or mRFP, revealing for the first time both separate and shared outflow circuitries among skeletal muscle and subcutaneous WAT and interscapular BAT. Prior PRV‐labeling studies from these tissues were mainly done using single injection sites, and our findings are concordant with earlier observations with respect to the identity of brain regions that project to gastrocnemius muscle, subcutaneous WAT and interscapular BAT (Adler et al, ; Bamshad et al, ; Cano et al, ; Kerman et al, , ; Nguyen et al, , ; Oldfield et al, ; Ryu et al, ; Wiedmann et al, ). Ours is the first co‐labeling study for these three tissue pairs, showing that cells in the PVN, PBN and brainstem and in multiple subregions thereof showed dual projections to muscle + WAT, muscle + BAT, and WAT + BAT.…”

Sympathetic innervation of the interscapular brown adipose tissue in mouse

“…Given the very small number of these neurons, they are not likely to be of major physiological importance. Our analysis of preganglionic neurons in the spinal cord is in general agreement with studies in the rat 39,46 and Siberian hamster, 44 which all report the stellate ganglion as a major contribution to the sympathetic innervation of the iBAT. How-ever, our data highlight the regional distribution of PRV labeling within the stellate ganglion and the lack of PRV labeling in the dorsal pole.…”

“…44 This is consistent with the overall development of sympathetic innervation that clearly dissociates the origin of sympathetic innervation in anterior (thorax and forelimbs), posterior (hind limb), and abdominal (situ) sites, 45 and classic views of autonomic innervation. 39 A few PRV-labeled neurons were found in DRG, and it is not clear whether these are true sympathetic efferent neurons or inadvertently anterograde labeled dorsal root afferents. Given the very small number of these neurons, they are not likely to be of major physiological importance.…”

Insights into the neurochemical signature of the Innervation of Beige Fat

“…The weight of evidence suggests that this must involve central integrated neural circuits [43] , [44] . In fact, a recent viral tracing study indicates that, coincident with the beiging of iWAT, there are changes in discrete supraspinal brain regions [45] , which, together with the shifts in gene expression in post ganglionic neurons described here, support the thesis that the beiging of WAT involves a coordinated response in the nervous system and targeted adipose tissue depot.…”