defective peripheral nerve development is linked to abnormal architecture and metabolic activity of adipose tissue in nscl-2 mutant mice缺陷周围神经发育异常有关建筑和nscl-2突变小鼠体内脂肪组织的代谢活动.pdfVIP

Defective Peripheral Nerve Development Is Linked to Abnormal Architecture and Metabolic Activity of Adipose Tissue in Nscl-2 Mutant Mice 1,2,4 1 ¨ 2 4 3 ¨ 2 Karen Ruschke , Henning Ebelt , Nora Kloting , Thomas Boettger , Kay Raum , Matthias Bluher , Thomas Braun1,4* 1 Institute of Physiological Chemistry, University of Halle-Wittenberg, Halle, Germany, 2 Department of Medicine, University of Leipzig, Leipzig, Germany, 3 Julius Wolff ´ ¨ Institute and Center for Musculoskeletal Surgery, Charite-Universitatsmedizin Berlin, Berlin, Germany, 4 Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany Abstract 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). Methodology: Changes in the architecture and innervation of WAT were compared between wildtype, Nscl2 2/ 2, ob/ob and Nscl2 2/ 2//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. Principal Findings: 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