Noradrenergic parenchymal nerve fiber branching after cold acclimatisation correlates with brown adipocyte density in mouse adipose organ

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Abstract
The mammalian adipose organ is composed of subcutaneous and visceral depots containing white and brown adipocytes. Cold acclimatisation induces an increase in the brown component without affecting the overall number of adipocytes; this form of plasticity is associated to obesity and diabetes resistance in experimental models. Cold activates the drive of the sympathetic nervous system to the adipose organ, where the vast majority of nerve fibers are in fact noradrenergic. However, it is unclear whether and how such fibers are involved in the plastic changes of the adipose organ. We thus conducted a systematic study of the distribution and number of sympathetic noradrenergic nerve fibers in the adipose organ of mice kept at different environmental temperatures. Adult Sv129 female mice were kept at 28 °C or 6 °C for 10 days. The density of tyrosine hydroxylase (noradrenergic)‐positive nerve fibers (no. of fibers per 100 adipocytes) was calculated in the subcutaneous and visceral depots of the adipose organ, and a correlation was sought between fiber density and proportion of brown adipocytes. Tyrosine hydroxylase‐positive parenchymal fibers were detected in all subcutaneous and visceral depots among white as well as brown adipocytes, the mediastinal depot displaying the densest innervation. Cold acclimatisation induced a threefold increase in the total number of TH fibers in the whole organ. The proportion of brown adipocytes positively correlated with noradrenergic fiber density in the organ. Taken together, these data suggest that cold acclimatisation induces noradrenergic fiber branching in the adipose organ of adult mice, and that such changes may be a precondition for its plastic transformation into a brown phenotype.