Sympathetic innervation of white adipose tissue and its regulation of fat cell number

Abstract

. Sympathetic innervation of white adipose tissue and its regulation of fat cell number. Am J Physiol Regul Integr Comp Physiol 286: R1167-R1175, 2004 10.1152/ajpregu.00558.2003.-White adipose tissue (WAT) is innervated by the sympathetic nervous system (SNS), and the central origins of this innervation have been demonstrated for inguinal and epididymal WAT (iWAT and eWAT, respectively) using a viral transneuronal tract tracer, the pseudorabies virus (PRV). Although the more established role of this sympathetic innervation of WAT is as a major stimulator of lipid mobilization, this innervation also inhibits WAT fat cell number (FCN); thus, local denervation of WAT leads to marked increases in WAT mass and FCN. The purpose of this study was to extend our understanding of the SNS regulation of FCN using neuroanatomical and functional analyses. Therefore, we injected PRV into retroperitoneal WAT (rWAT) to compare the SNS outflow to this pad from what already is known for iWAT and eWAT. In addition, we tested the ability of local unilateral denervation of rWAT or iWAT to promote increases in WAT mass and FCN vs. their contralateral neurally intact counterparts. Although the overall pattern of innervation was more similar than different for rWAT vs. iWAT or eWAT, its SNS outflow appeared to involve more neurons in the suprachiasmatic and solitary tract nuclei. Denervation produced significant increases in WAT mass and FCN for both iWAT and rWAT, but FCN was increased significantly more in iWAT than in rWAT. These data suggest differences in origins of the sympathetic outflow to WAT and functional differences in the WAT SNS innervation that could contribute to the differential propensity for fat cell proliferation across WAT depots in vivo. body fat; cellularity; hyperplasia; pseudorabies virus; tract tracing; white fat ENERGY BALANCE IS MAINTAINED through alterations in energy intake and energy expenditure. Lipid is the primary form of stored energy in mammals and is largely found in white adipose tissue (WAT) as triacylglycerols. Prolonged positive energy balance promotes obesity that in humans is associated with a number of health risks (34). The deposition of lipid initially results in increases in fat cell size (FCS), but soon triggers increases in fat cell number (FCN; for review, see Ref. 16). The processes underlying this hypercellularity, a hallmark sign of obesity, are not well understood (for review, see Ref. 21). Furthermore, the accretion of lipid in and of itself is not necessarily associated with these health risks (38); rather it is the distribution of body fat that is critical (19). That is, visceral obesity is closely associated with development of the "metabolic syndrome" and type II diabetes (for review, see Ref. 44). Thus understanding how body fat is preferentially deposited and mobilized is necessary for the prevention and treatment of obesity, respectively.One mechanism that may underlie the differential accumulation of lipid by WAT depots, as well as the differential mobilization of lipid, i...

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“…Paraventricular nucleus (PVN) CRH neurons innervate WAT directly (32,33). The PVN neurons that send projections to WAT are innervated by POMC neurons from the arcuate nucleus, which express MC3-R, and by NPY neurons in the nucleus of the solitary tract (31).…”

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“…The reason for this fat-pad variation is not entirely clear, however, a likely explanation is that fat-pads differ in the density of sympathetic innervation 50,51 and/or cell-autonomous inducibility of molecular pathways of brown fat adipogenesis. 18 Supporting the former, it has been shown that the number of sympathetic nerve fibers correlates positively with the density of brown adipocytes in WAT 52 and that norepinephrine concentration varies among fat pads, being higher, for example, in retroperitoneal than epididymal fat pads in Siberian hamsters.…”

“…18 Supporting the former, it has been shown that the number of sympathetic nerve fibers correlates positively with the density of brown adipocytes in WAT 52 and that norepinephrine concentration varies among fat pads, being higher, for example, in retroperitoneal than epididymal fat pads in Siberian hamsters. 50,51 With respect to cell-autonomous inducibility of molecular pathways of brown fat adipogenesis, it has been shown that mRNA expression of Prdm16 is higher in inguinal than epididymal fat pads in B6 mice, and that adipose tissue overexpression of Prdm16 on this genetic background results in emergence of brown-like adipocytes in inguinal but not in epididymal fat pads. 18 The retroperitoneal and inguinal fat pads (but not epididymal fat pads to our knowledge) showed emergence of brown fat (in response to cold or b 3 -stimulation) in several previous studies.…”

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