Brown adipose tissue (BAT) is responsible for the dissipation of energy in response to either a lowered ambient temperature or elevated caloric intake. It was recently discovered that white adipose tissue (WAT) can be transformed to “brown-like” (beige) fat which has necessitated a more complete understanding of the central neural control of this “brown-like” fat cell function.
To interrogate multisynaptic neural inputs to brown, white, and “beige” fat compartments, injection of pseudorabies virus (PRV Bartha) with different fluorescent reporters (PRV-green/PRV-red) were made in the same rats into 1) interscapular BAT and 2) inguinal WAT either at a) room temperature or b) “beiged” by exposure to 8°C for 7 days. Animals were allowed to survive for 5 days post inoculation to allow for transynaptic transport of virus through the autonomic neuraxis. Subsequent histological analysis allowed the identification of viral-infected neurons in the paravertebral ganglia, spinal cord, brain stem, midbrain and hypothalamus. Animals within a second cohort, without injection of PRV, had paravertebral ganglia micro-dissected (stellate projecting to BAT and T13/L1 projecting to WAT or beiged WAT). Through a combination of RNA-seq technologies and bioinformatics, the differential gene expression between neural inputs to BAT, WAT and beiged WAT was determined.
Histological analysis indicated ‘private lines’ of communication to various fat pads, and populations of “command neurons” which had collateral axonal projections to different fat pads including both brown and white. Moreover, the relative percentage of these “command neurons” projecting to BAT and beige WAT increased under conditions of cold exposure. Specific genes were identified providing a “signature” of the projections to beiged WAT.
These data provide key insights into the prevalence of command neurons involved in both storage and burning of energy and the neuroanatomical and neurochemical bases of the innervation of brown, white and white fat transformed into beige fat.