Mechanisms Controlling Adipose Tissue Metabolism by the Sympathetic Nervous System: Anatomical and Molecular Aspects

Abstract

The relative degree of adipose tissue responsiveness to catecholamines reflects the balance of multiple forces, each of which are shaped by a combination of genetic and environmental factors. On the genetic side are the developmentally programmed patterns and density of innervation into various adipose depots, and the amounts and types of the specific adrenergic receptors (ARs) and their metabolic targets that are expressed on the adipocytes within different depots. Within the latter aspect is whether the receptors are stimulatory (βARs) or inhibitory (αARs) for lipolysis, their coupling efficiency to the downstream signaling molecules, and the relative kinetic activity of those regulated enzymes, scaffolding proteins and transcription factors. Finally, there is the genetic profile that predisposes preadipocytes toward the progression of the brown versus white adipocyte phenotype. On the environmental side, diet contributes to the relative degree of adipose tissue response to catecholamines by altering the hormonal and metabolic signals that control important adipocyte genes. These include the ARs themselves, the kinase pathways ARs regulate, and hence also the ability to determine decisions about fat storage versus thermogenesis. With our increased understanding of the SNS circuitry from the CNS to adipose tissue and the newer appreciation of signaling pathways that are activated in adipocytes by catecholamines, science is positioned in the future to better define the molecular and genetic regulatory points that determine adipose tissue sensitivity to dietary and other environmental forces, and to establish the underlying basis for the molecular decisions that drive a cell to become a white or brown fat cell. Such new insights that will be gained as a result will hopefully generate new therapeutic targets and approaches against the obesity epidemic in our midst.

Neural innervation of white adipose tissue and the control of lipolysis

“…The classic studies of Lafontan, Langin and associates [44;166;174;199] discovered, clarified and highlighted the role of white adipocyte receptors in catecholamine and thus principally, SNS-induced lipolysis (for review see: [162;163]). From these and subsequent confirmatory studies, they unequivocally demonstrated that the balance between the stimulation of lipolysis by β-ARs (subtypes β-AR 1–3 ) and its inhibition by α 2 -ARs dictates the degree of lipolysis if all other factors affecting lipolysis are equivalent [56;161;165]. Therefore, when β-AR activation predominates, lipolysis increases and when α 2 -AR activation predominates, lipolysis is inhibited [160;162].…”

Sensory and sympathetic nervous system control of white adipose tissue lipolysis

“…The studies of Lafontan, Langin and associates (Carpene et al 1993;Lafontan et al 1979;Langin et al 1991;Mauriege et al 1988) have clearly delineated the function and importance of the white adipocyte adrenoceptors for catecholamine-associated lipolysis [for review see: (Lafontan et al 1985;Lafontan and Berlan 1995)]. An unambiguous and well-substantiated outcome of their work is the notion that the balance between lipolysis-promoting β-adrenoceptor (β-AR) subtype 1-3 (ß-AR 1-3 ) activation and lipolysis-inhibiting α 2 -AR activation dictates the degree of lipolytic status of the adipocyte, all other factors being equal (Collins et al 2007;Lafontan et al 1995;Lafontan and Berlan 1993). Thus, when ß-AR activation predominates [in rodents, primarily the β 3 -ARs (Collins, Migliorini, & Bartness 2007)], lipolysis is stimulated and, conversely, when α2-AR activation predominates, lipolysis is inhibited (Lafontan 1994;Lafontan & Berlan 1995).…”

“…An unambiguous and well-substantiated outcome of their work is the notion that the balance between lipolysis-promoting β-adrenoceptor (β-AR) subtype 1-3 (ß-AR 1-3 ) activation and lipolysis-inhibiting α 2 -AR activation dictates the degree of lipolytic status of the adipocyte, all other factors being equal (Collins et al 2007;Lafontan et al 1995;Lafontan and Berlan 1993). Thus, when ß-AR activation predominates [in rodents, primarily the β 3 -ARs (Collins, Migliorini, & Bartness 2007)], lipolysis is stimulated and, conversely, when α2-AR activation predominates, lipolysis is inhibited (Lafontan 1994;Lafontan & Berlan 1995). Participation of each of the three ß-adrenoceptor subtypes in lipolysis varies with several factors, including the WAT depot, animal species and its sex, age or degree of obesity [ e.g.…”

Thematic review series: Adipocyte Biology. Sympathetic and sensory innervation of white adipose tissue

“…In the process of conducting this work, we discovered the importance of the sympathetic nervous system (SNS) in lipid mobilization from white adipose tissue (WAT) as well as more recently realizing the possible importance of the sensory innervation of WAT. Several overviews of the role of the SNS in lipid mobilization were published recently (8)(9)(10)(11). To give a better understanding of how we came to the realization that lipid mobilization occurs primarily through the sympathetic innervation of WAT, we will describe some background studies focused on the reversal of photoperiod-induced obesity that ultimately led us to define and test the SNS innervation of WAT.…”