Premium
Coordination of Homeostatic Functions by Intrascapular Brown Adipose Tissue‐ and Pancreas‐related Command Neurons
Author(s) -
Butcher Sierra Morgan,
Hamling Brooke Victoria,
Desmoulins Lucie Delphine,
Zsombok Andrea
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.766.3
Subject(s) - hypothalamus , energy homeostasis , brainstem , endocrinology , medicine , homeostasis , biology , glucose homeostasis , stimulation , brown adipose tissue , adipose tissue , neuroscience , insulin , insulin resistance , obesity
Preautonomic neurons located in the brainstem and hypothalamus influence glucose metabolism, food intake, and energy homeostasis through outputs to visceral organs. The existence of command neurons (neurons with connections to multiple organs) suggests that coordinated autonomic output modulates homeostasis. In this study, we identified command neurons related to the pancreas and the intrascapular brown adipose tissue (iBAT) using isogenic strains of pseudorabies virus (PRV), PRV‐614 and PRV‐152, respectively. Co‐localization of the two PRVs identified iBAT‐pancreas command neurons in the brainstem and hypothalamus in male C57bl/6J mice. Command neurons were also identified in the parasubthalamic nucleus (PSTN), a subnucleus of the lateral hypothalamus that serves as a conduit between the brainstem and hypothalamus and has previously been implicated in food intake and cardiovascular function. Since the pancreas and the iBAT are important for glucose and energy homeostasis, we hypothesized that stimulation of the PSTN modulates food consumption and glucose tolerance. A viral construct (stimulatory designer receptor exclusively activated by designer drugs) was injected to the PSTN. Following a fasting period, mice received an i.p. injection of clozapine‐N‐oxide (CNO, 1mg/kg) to activate PSTN neurons 30 minutes prior to the reintroduction of food or a glucose challenge (2 g/kg). Stimulation of the PSTN increased food intake during the first 30 minutes of feeding. The average food intake in mice that received CNO was 0.052 ± 0.0076 g of food ingested/g of body weight, while the average in those that received vehicle was 0.0346 ± 0.0036 g of food ingested/g of body weight (p=0.0468, n=8). The average cumulative food intake after 6 hours was significantly increased in mice treated with CNO compared to vehicle injected mice (0.1386 ± 0.0177 g of food ingested/g of body weight vs. 0.0984 ± 0.005 g of food ingested/g of body weight) (p<0.05, n=8). On the other hand, stimulation of the PSTN did not alter glucose tolerance. The average area under the curve (AUC) was not significantly different among the groups (CNO and glucose: 1362.98 ± 60.52 AUC, vehicle and glucose: 915.37 ± 27.71 AUC, CNO and saline: 1156.51 ± 53.31 AUC) (p>0.05, n=8). These findings revealed that stimulation of the PSTN increased cumulative food intake but had no effect on glucose tolerance. In summary, our study demonstrates the existence of iBAT‐pancreas command neurons in brain areas including the PSTN and suggests that the PSTN is involved in the control of food intake. Support or Funding Information National Institutes of Health R01 DK099598 for AZ Board of Regents for BH Core Facilities (Tulane School of Medicine and Louisiana State University Health Sciences Center) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .