Sympathetic nerve development in the brown adipose tissue of the rat

Abstract

With the Falck fluorescent histochemical method for catecholamines, the development of sympathetic nerve fibers in the brown fat of the rat was studied. At birth a low level of catecholamine fluorescence was found in preterminal axon bundles, which have been called here sheathed axons. The fluorescence in these bundles reached a maximum at about 5 days of age. Parenchymal nerve catecholamine fluorescence was discernible at 2 to 3 days of age. These nerves progressively got brighter until adult levels had been reached at about 10–15 days. The sympathetic nerve fiber network seen on arterial blood vessels in the adult was not seen in the young rat until 8–10 days of age. These blood vessel nerves reached maturity at about 15–21 days. The parenchymal nerve innervation was shown to originate in the sympathetic chain. The sympathetic chain gave off sheathed axon bundles which reach the parenchyma by passing along septa or beside blood vessels.

Developmental influences on circuits programming susceptibility to obesity

“…FGF21 treatment in neonates is sufficient to increase thermogenic genes and core body temperature [97]. The initial phase of BAT recruitment at parturition is likely independent of sympathetic inputs because there are very few autonomic projections to BAT that can be detected at birth [98]. Thus, the collective action of neuroendocrine, cold-induced and dietary factors within first 2 days of birth likely explain the onset of cold-induced thermogenesis at P2-5 [91,99], a behavior that is critical for survival.…”

“…In the adult, input from the sympathetic nervous system (SNS) to BAT is the major driver of cold-induced thermogenesis [89]. Sympathetic nerves innervate BAT by P6, and the dramatic increase in the capacity for cold-induced thermogenesis between P10-15 [99] coincides with an expansion in the catecholaminergic innervation of the BAT parenchyma [98](Figure 3). Ucp1 , a molecular indicator of BAT activity, reaches adult levels by P16 [100].…”

“…These observations support the idea that leptin plays a role in “unmasking” BAT after birth and maintaining baseline thermogenic activity of BAT. In principle, leptin could mediate these effects via direct effects on BAT to promote lipolysis [116] and/or indirect stimulation of the earliest sympathetic projections to BAT [98]. …”

“…LepR is not yet detected in the mediobasal hypothalamus at this time [74,75]. The observation that neonatal BAT does not receive catecholaminergic input at birth [98], argues against a role for leptin signaling in other brain regions in the initial phase of BAT recruitment. It is possible that early effects of leptin are mediated by direct signaling within BAT [116] or indirect actions on other endocrine organs.…”

Temperature-Sensitive Phenotype in Mice Lacking Pituitary Adenylate Cyclase-Activating Polypeptide

“…Preganglionic sympathetic nerves synapse onto postganglionic neurons in the middle and inferior cervical ganglia and in the first five thoracic ganglia (25). These postganglionic nerves innervate brown adipocytes and the blood vessels within brown adipose tissue to activate heat production and distribution, respectively (26). Norepinephrine is released from sympathetic nerve endings and binds to ␤ 3 -adrenergic receptors on brown adipocytes activating hormone sensitive (HS) lipase and uncoupling protein (UCP) 1 (27).…”