Characteristics of the α₂/β‐adrenoceptor‐coupled adenylate cyclase system and their relationship with adrenergic responsiveness in hamster fat cells from different anatomical sites

Abstract

Various studies have shown that the lipolytic response of white adipocytes to catecholamines was dependent on the anatomical origin of these cells. To provide a biological explanation for this phenomenon, we compared hamster white adipocytes, from femoral subcutaneous and epididymal fat, for their lipolytic activities, cAMP responses and adrenoceptor-coupled adenylate cyclase system. Basal and maximal lipolytic responses to the b-adrenergic (isoproterenol) and the mixed a2/Padrenergic (epinephrine) agonists were lower in femoral subcutaneous cells than in epididymal cells, but the a,-adrenergic antilipolytic response to 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline bitartate (UK14304) was slightly greater in femoral subcutaneous fat cells than in epididymal fat cells. Identical results were observed for cAMP responses, except for the a,-adrenergic inhibitory response which was identical in both fat deposits. Adrenoceptors studies revealed higher density of inhibitory a,-adrenoceptors 2-(2-methoxy-l,4-benzodioxan-2-yl)-2-imidazoline ([3H]RX821002-binding sites) in femoral subcutaneous fat cells than in epididymal fat cells, but identical density of stimulatory badrenoceptors ('251-cyanopindolol-binding sites) and similar subdivision into b-adrenoceptor subtypes in both adipose deposits. Finally, the level of the a-subunits of the stimulatory and inhibitors guanine-nucleotide-binding regulatory proteins, as well as the adenylate cyclase catalytic activity were 40 -50% lower in femoral subcutaneous fat cell membranes than in epididymal fat cell membranes. These results suggest that the differences in cAMP and lipolytic responses to catecholamines between epididymal and femoral subcutaneous adipocytes result at least in part from site-related differences in the adenylate cyclase system rather than in the adrenoceptor status.It is now well established that fat distribution and adipocyte metabolic activity are variable according to sex and the type of obesity. For example, women preferentially accumulate fat in the hip region, while in men fat deposits are mainly located in the upper part of the body. Moreover, for the same individual, the lipolytic activity of white fat cells in response to catecholamines is different from one anatomical site to another [l -41. In fact, several studies focused on human adipose tissue have revealed that fat cells from the femoral subcutaneous region had a lower lipolytic response toCorrespondence to

Gender- and site-related effects on lipolytic capacity of rat white adipose tissue

“…Thus, although both tissues had a similar basal lipolysis, gonadal fat had a greater capacity to activate lipolysis in response to catecholamines, as a result of a signal transduction system which was more focused toward lipid mobilization, both at the AR step and at the postreceptor step. Similar results have been reported by other authors [9 -14, 18], who have found differences between depots in the expression of the different adrenoceptor subtypes [16,24,25], as well as in other steps of the lipolytic pathway [9,10,13,25]. Altogether, these results suggest essential differences in the pattern of gene expression between the different fat depots that could be related to different programs of differentiation and maturation of adipocytes.…”

“…The marked variations in fat cell metabolism depending on anatomical location are of potential pathophysiological interest in human metabolic disorders associated with obesity, such as dyslipidemia, diabetes mellitus, and hypertension, in particular when fat is mainly accumulated in the visceral depot [21 -23]. Several mechanisms, affecting various steps of the lipolytic cascade, have been proposed to explain the site-specific differences in lipolysis: from the a 2 / b-AR balance [16,24,25], to steps at the postreceptor level, including adenylate cyclase activity [13], as well as HSL activity and expression [9,10,25]. Moreover, variations in lipolytic activity have also been shown to be gender dependent.…”

Fat Cell α2-Adrenoceptors: The Regulation of Fat CellFunction and Lipolysis*

“…There is a smaller a 2 -component in the regulation of lipolysis in omental than in subcutaneous adipose tissues in humans (68,112,113). Differences in a 2 -and j3-adrenergic effects in the control of lipolysis (31,111,114,115) and heterogeneous distribution of j3-and a 2adrenoceptors have been described in fat cells originating from deposits located in different anatomical sites in various species (hamster, dog, rat, and rabbit) (27,30,86,(116)(117)(118). In human fat cells, the regional differences in catecholamineinduced lipolysis are regulated at the adrenoceptor level chiefly because of site variations in )3-and a 2 -adrenoceptor density (68) (Fig.…”

“…In human fat cells, the regional differences in catecholamineinduced lipolysis are regulated at the adrenoceptor level chiefly because of site variations in )3-and a 2 -adrenoceptor density (68) (Fig. Gs/Gi protein ratio and intrinsic activity of the catalytic subunit of the adenylylcyclase (118). Although less well defined, differences could also exist in the functional capacities of the other elements of the adenylylcyclase-transducing system in fat cells of humans and other species, e.g.…”

Pregnancy modifies the α2-β-adrenergic receptor functional balance in rabbit fat cells

“…In these species (including humans), adipocytes exhibit a lower lipolytic response to epinephrine or norepinephrine than isoproterenol (which activates solely ␤ -adrenergic receptors), and the use of ␣ 2-antagonist agents clearly demonstrates that stimulation of ␣ 2-adrenergic receptors is responsible for this weak lipolytic responsiveness to catecholamines. Alongside species-specific variations, physiological factors such as age (5,6,(8)(9)(10), fat cell size (5,6), fat deposit location (11)(12)(13), and adiposity (12,14,15) have an effect on adipocyte ␣ 2-adrenergic responsiveness, resulting in modifications of the overall adrenergic control of lipolysis (for a review see ref. 16).…”