Selective parasympathetic innervation of subcutaneous and intra-abdominal fat — functional implications

Abstract

The wealth of clinical epidemiological data on the association between intra-abdominal fat accumulation and morbidity sharply contrasts with the paucity of knowledge about the determinants of fat distribution, which cannot be explained merely in terms of humoral factors. If it comes to neuronal control, until now, adipose tissue was reported to be innervated by the sympathetic nervous system only, known for its catabolic effect. We hypothesized the presence of a parasympathetic input stimulating anabolic processes in adipose tissue. Intra-abdominal fat pads in rats were first sympathetically denervated and then injected with the retrograde transneuronal tracer pseudorabies virus (PRV). The resulting labeling of PRV in the vagal motor nuclei of the brain stem reveals that adipose tissue receives vagal input. Next, we assessed the physiological impact of these findings by combining a fat pad-specific vagotomy with a hyperinsulinemic euglycemic clamp and RT-PCR analysis. Insulin-mediated glucose and FFA uptake were reduced by 33% and 36%, respectively, whereas the activity of the catabolic enzyme hormone-sensitive lipase increased by 51%. Moreover, expression of resistin and leptin mRNA decreased, whereas adiponectin mRNA did not change. All these data indicate an anabolic role for the vagal input to adipose tissue. Finally, we demonstrate somatotopy within the central part of the autonomic nervous system, as intra-abdominal and subcutaneous fat pads appeared to be innervated by separate sympathetic and parasympathetic motor neurons. In conclusion, parasympathetic input to adipose tissue clearly modulates its insulin sensitivity and glucose and FFA metabolism in an anabolic way. The implications of these findings for the (patho)physiology of fat distribution are discussed.

Fat storage is partially dependent on vagal activity and insulin secretion of hypothalamic obese rat

“…In addition, norepinephrine turnover is very low in WAT and BAT, as recorded in MSG-mice [40,41]. Although direct SNS controls fat tissue accumulation, rare evidences [42] exist which show direct effect of parasympathetic nervous system (PNS) on WAT and BAT metabolism. Nevertheless, the presence of PNS terminals on fat tissues has not been demonstrated [43].…”

Neural regulators of innate immune responses and inflammation

“…Histamine also negatively regulates neutrophil infiltration via H2 receptors in allergic inflammation [76]. A very recent study has demonstrated that the vagus nerve innervates adipose tissue; the physiological impact of this innervation is associated with selective induction of endocrine function and leptin release [77]. Although the implication of leptin in chronic inflammation and rheumatoid diseases, respectively, remains controversial [78], a number of studies demonstrate a protective role for leptin in inflammation [79][80][81][82][83].…”

Pediatric Endocrine Disorders of Energy Balance

“…Retrograde tracing of white adipose tissue reveals a wealth of efferents originating at the DMV [77]. These efferents synapse on the M 1 muscarinic receptor on the adipocyte, which increases insulin sensitivity of the adipocyte.…”