Abstract
BackgroundThe combination of oleoyl-estrone (OE) and a selective β3-adrenergic agonist (B3A; CL316,243) treatment in rats results in a profound and rapid wasting of body reserves (lipid).MethodsIn the present study we investigated the effect of OE (oral gavage) and/or B3A (subcutaneous constant infusion) administration for 10 days to overweight male rats, compared with controls, on three distinct white adipose tissue (WAT) sites: subcutaneous inguinal, retroperitoneal and epididymal. Tissue weight, DNA (and, from these values cellularity), cAMP content and the expression of several key energy handling metabolism and control genes were analyzed and computed in relation to the whole site mass.ResultsBoth OE and B3A significantly decreased WAT mass, with no loss of DNA (cell numbers). OE decreased and B3A increased cAMP. Gene expression patterns were markedly different for OE and B3A. OE tended to decrease expression of most genes studied, with no changes (versus controls) of lipolytic but decrease of lipogenic enzyme genes. The effects of B3A were widely different, with a generalized increase in the expression of most genes, including the adrenergic receptors, and, especially the uncoupling protein UCP1.DiscussionOE and B3A, elicit widely different responses in WAT gene expression, end producing similar effects, such as shrinking of WAT, loss of fat, maintenance of cell numbers. OE acted essentially on the balance of lipolysis-lipogenesis and the blocking of the uptake of substrates; its decrease of synthesis favouring lipolysis. B3A induced a shotgun increase in the expression of most regulatory systems in the adipocyte, an effect that in the end favoured again the loss of lipid; this barely selective increase probably produces inefficiency, which coupled with the increase in UCP1 expression may help WAT to waste energy through thermogenesis.ConclusionsThere were considerable differences in the responses of the three WAT sites. OE in general lowered gene expression and stealthily induced a substrate imbalance. B3A increasing the expression of most genes enhanced energy waste through inefficiency rather than through specific pathway activation. There was not a synergistic effect between OE and B3A in WAT, but their combined action increased WAT energy waste.
Highlights
The combination of oleoyl-estrone (OE) and a selective b3-adrenergic agonist (B3A; CL316,243) treatment in rats results in a profound and rapid wasting of body reserves
B3A increasing the expression of most genes enhanced energy waste through inefficiency rather than through specific pathway activation
The main elements that white adipose tissue (WAT) employs in this regulative role are: a) its large capability to store energy as triacylglycerols, depleting circulating levels [4], a function that extends in part to the removal of excess glucose [5] used for lipogenesis [6]; b) its ability to reverse the storage process, releasing fatty acids to the bloodstream through lipolysis [7]; c) the modulation of other tissues through the secretion of hormones and paracrine agents [8]; and d) the wasting of energy, a postulated role [9] traditionally attributed to brown adipose tissue, and insufficiently characterized in WAT
Summary
The combination of oleoyl-estrone (OE) and a selective b3-adrenergic agonist (B3A; CL316,243) treatment in rats results in a profound and rapid wasting of body reserves (lipid). Oleoyl-estrone (OE) is a signalling molecule from WAT that has been postulated as a ponderostat modifying agent [10], since its administration induces a severe wasting of the body fat reserves [11], reducing WAT lipogenesis and substrate uptake rather than elicit increases in lipolysis, increasing fatty acid output [12]. This process is in part mediated, at least in liver, by SREBP1c [13], under conditions in which glycolysis is not completely blocked irrespective of a large availability of fatty acids [14]. OE reduces WAT mass at the expense of a decrease in energy intake with maintained thermogenesis [16,17], whilst most b3-adrenergic agonists elicit a massive lipolysis to fuel an increased thermogenesis, but barely affect food intake [18], and tend to show limited effects because of downregulation of the receptors [19]
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