Sympathetic and sensory innervation of brown adipose tissue

Abstract

The innervation of brown adipose tissue (BAT) by the sympathetic nervous system (SNS) is incontrovertible and, with its activation, functions as the principal, if not exclusive, stimulator of BAT thermogenesis. The parasympathetic innervation of BAT only appears in two minor BAT depots, but not in the major interscapular BAT (IBAT) depot. BAT thermogenesis is triggered by the release of norepinephrine from its sympathetic nerve terminals, stimulating β3-adrenoceptors that turns on a cascade of intracellular events ending in activation of uncoupling protein-1 (UCP-1). BAT also has sensory innervation that may function to monitor BAT lipolysis, a response necessary for activation of UCP-1 by fatty acids, or perhaps responding in a feedback manner to BAT temperature changes. The central sympathetic outflow circuits ultimately terminating in BAT have been revealed by injecting the retrograde viral transneuronal tract tracer, pseudorabies virus, into the tissue; moreover, there is a high degree of colocalization of melanocortin 4-receptor mRNA on these neurons across the neural axis. The necessary and sufficient central BAT SNS outflow sites that are activated by various thermogenic stimuli are not precisely known. In a chronic decerebration procedure, IBAT UCP-1 gene expression can be triggered by fourth ventricular injections of melanotan II, the melanocortin 3/4 receptor agonist, suggesting that there is sufficient hindbrain neural circuitry to generate thermogenic responses with this stimulation. The recent recognition of BAT in normal adult humans suggests a potential target for stimulation of energy expenditure by BAT to help mitigate increased body fat storage.

Temperature-associated suicide mortality: contrasting roles of climatic warming and the suicide prevention program in Finland

“…Currently, it cannot be ruled out that the central sensory circuits projecting from BAT to the brain [52,53] might provide a pathway, through the ventromedial hypothalamus [54] to the periaqueductal gray areas [55,56] that are key regions involved in anxiety [57,58], which we hypothesize to mediate the effect of over-activated BAT in those affected. However, the over-activated BAT is tightly involved in abnormalities in the thermoregulatory mechanisms that characterize individuals prone to depressive episodes [59][60][61][62].…”

Sympathetic nervous system behavior in human obesity

“…Second, the sympathetic nervous system innervates white adipose tissue and plays an important role in lipid mobilization (Bartness and Song, 2007). In humans, stimulation of the lateral femoral cutaneous nerve elicits lipolysis in the innervation area (Dodt et al, 1999).…”

“…Whether the reduced SNS activity to white adipose tissue observed in obese subjects (Coppack et al, 1998) contributes to a corresponding lower basal rate of lipolysis (relative to fat mass) (Klein et al, 1988) is not known. In addition, SNS activity to white adipose tissue also has an inhibitory influence on fat cell proliferation (Bartness and Song, 2007). Therefore, it is also possible that the lower SNS activity to white adipose tissue in obesity may be associated with fat cell proliferation (Bartness and Song, 2007).…”

“…In addition, SNS activity to white adipose tissue also has an inhibitory influence on fat cell proliferation (Bartness and Song, 2007). Therefore, it is also possible that the lower SNS activity to white adipose tissue in obesity may be associated with fat cell proliferation (Bartness and Song, 2007). However, it is important to emphasize that it is not known whether SNS activity to white adipose tissue is specifically reduced in different obesity phenotypes (e.g., visceral obesity).…”

Genetics, physiology and perinatal influences in childhood obesity: view from the Chair

“…Obesity results from chronic imbalances between energy intake and expenditure, individual differences in energy metabolism, sympathetic innervation, 4 and adipose cell growth, proliferation and death. 5 Important parameters of WAT include cell number and triglyceride (TG) storage (measured by fat mass, adipocyte size, TG synthesis), anatomical location, adipocytokine secretion and lipolysis.…”