Sympathetic but not sensory denervation stimulates white adipocyte proliferation.
White adipocyte proliferation is a hallmark of obesity, but it largely remains a mechanistic mystery. We and others previously demonstrated that surgical denervation of white adipose tissue (WAT) triggers increases in fat cell number, but it is unknown whether this was due to preadipocyte proliferation or maturation of existing preadipocytes that allowed them to be counted. In addition, surgical denervation severs not only sympathetic but also sensory innervation of WAT. Therefore, we tested whether sympathetic WAT denervation triggers adipocyte proliferation using 5-bromo-2'-deoxyuridine (BrdU) as a marker of proliferation and quantified BrdU-immunoreactive (ir) cells that were co-labeled with AD-3-ir, an adipocyte-specific membrane protein marker. The unilateral denervation model was used for all experiments where Siberian hamster inguinal WAT (IWAT) was unilaterally denervated, the contralateral pad was sham denervated serving as a within-animal control, and then BrdU was injected systemically for 6 days. When IWAT was surgically denervated, severing both sympathetic and sensory nerves, tyrosine hydroxylase (TH)-ir, a sympathetic nerve marker, and calcitonin gene-related peptide (CGRP)-ir, a sensory nerve marker, were significantly decreased, and BrdU+AD-3-ir adipocytes were increased approximately 300%. When IWAT was selectively sensory denervated via local microinjections of capsaicin, a sensory nerve-specific toxin, CGRP-ir, but not TH-ir, was decreased, and BrdU+AD-3-ir adipocytes were unchanged. When IWAT was selectively sympathetically denervated via local microinjections of 6-hydroxy-dopamine, a catecholaminergic-specific toxin, TH-ir, but not CGRP-ir, was significantly decreased, and BrdU+AD-3-ir adipocytes were increased approximately 400%. Collectively, these data provide the first direct evidence that sympathetic nerves inhibit white adipocyte proliferation in vivo.
Foster
Michelle T
MT
Department of Biology, Georgia State University, 24 Peachtree Center Avenue NE, Atlanta, GA 30302-4010, USA.
Bartness
Timothy J
TJ
D000222:Adaptation, Physiological / Q000502:physiology; D052438:Adipocytes, White / Q000166:cytology / Q000502:physiology*; D052436:Adipose Tissue, White / Q000166:cytology / Q000294:innervation* / Q000502:physiology* / Q000601:surgery; D000344:Afferent Pathways / Q000502:physiology* / Q000601:surgery; D000818:Animals; D049109:Cell Proliferation; D006224:Cricetinae; D003714:Denervation; D008297:Male; D009433:Neural Inhibition / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D017111:Phodopus; D013564:Sympathetic Nervous System / Q000502:physiology* / Q000601:surgery