Defective peripheral nerve development is linked to abnormal architecture and metabolic activity of adipose tissue in Nscl-2 mutant mice.
BACKGROUND
In mammals the interplay between the peripheral nervous system (PNS) and adipose tissue is widely unexplored. We have employed mice, which develop an adult onset of obesity due to the lack the neuronal specific transcription factor Nscl-2 to investigate the interplay between the nervous system and white adipose tissue (WAT).


METHODS
Changes in the architecture and innervation of WAT were compared between wildtype, Nscl2-/-, ob/ob and Nscl2-/-//ob/ob mice using morphological methods, immunohistochemistry and flow cytometry. Metabolic alterations in mutant mice and in isolated cells were investigated under basal and stimulated conditions.


RESULTS
We found that Nscl-2 mutant mice show a massive reduction of innervation of white epididymal and paired subcutaneous inguinal fat tissue including sensory and autonomic nerves as demonstrated by peripherin and neurofilament staining. Reduction of innervation went along with defects in the formation of the microvasculature, accumulation of cells of the macrophage/preadipocyte lineage, a bimodal distribution of the size of fat cells, and metabolic defects of isolated adipocytes. Despite a relative insulin resistance of white adipose tissue and isolated Nscl-2 mutant adipocytes the serum level of insulin in Nscl-2 mutant mice was only slightly increased.


CONCLUSIONS
We conclude that the reduction of the innervation and vascularization of WAT in Nscl-2 mutant mice leads to the increase of preadipocyte/macrophage-like cells, a bimodal distribution of the size of adipocytes in WAT and an altered metabolic activity of adipocytes.
Institute of Physiological Chemistry, University of Halle-Wittenberg, Halle, Germany.
Karen
K
Ruschke
Henning
H
Ebelt
Nora
N
Klöting
Thomas
T
Boettger
Kay
K
Raum
Matthias
M
Blüher
Thomas
T
Braun
D052436:Adipose Tissue, White / Q000294:innervation* / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D010525:Peripheral Nerves / Q000254:growth & development*
D051792:Basic Helix-Loop-Helix Proteins; D005947:Glucose; D007328:Insulin; D020738:Leptin; C484104:Nhlh2 protein, mouse