Estradiol does not directly regulate adipose lipolysis

Abstract

The mechanisms by which estradiol modulates adipose lipolysis are poorly understood. We sought to measure basal and b 3 -stimulated indices of lipoysis (FFAs, glycerol) in vivo in E2 deficient or supplemented rats, and ex vivo with direct acute E2 exposure. For 2 weeks, ovariectomized (OVX) and OVX rats treated with a daily oral dose of E2 (OVX E2) were pairfed to SHAM controls (n D 12 per group). Adipocyte size was modestly (»40%) increased in OVX rats, but did not reach significance (p D 0.2). After 2 weeks, half of the animals in each group received an in vivo injection of saline or 1 mg/kg of the b3 agonist CL 316, 243. Serum FFA concentrations, but not glycerol, were lower in OVX and OVX E2 rats compared with SHAM controls (p D 0.02). A significant CL response was present in all groups (p<0.001) and HSL activation was unaffected by OVX or OVX E2 in retroperitoneal (r.p.) or inguinal (iWAT) adipose depots in vivo. Ex vivo, CL increased FFA and glycerol accumulation in the media as well as HSL phosphorylation by several fold in r.p. and iWAT explants, but responses from OVX and OVX E2 rats were comparable to SHAMs. To assess whether E2 can directly affect lipolysis, r.p. and iWAT tissue was treated with E2, CL or E2 C CL for 2, 4 or 8 hours using adipose tissue organ culture. CL stimulated FFA release (p<0.001), but was unaffected by E2. Overall, our results indicate that E2 does not directly regulate adipose tissue lipolysis.

Acylated and unacylated ghrelin directly regulate ß-3 stimulated lipid turnover in rodent subcutaneous and visceral adipose tissue ex vivo but not in vivo

“…Other in vivo work 4 has demonstrated significant metabolic and physiological effects using a similar injection dose of ghrelin. Also, previous work in our lab 13 has demonstrated a robust increase in lipolysis following CL administration by 30 min. As such, this time point was used for blood and tissue collection.…”

“…Previous work has found that these doses for AG, UnAG and CL elicit significant metabolic effects; the dose used for GH represents a concentration that is achieved in response to ghrelin administration in rats. 7,10,13 Sampling of media for the quantification of glycerol and free fatty acids was done at t = 2, 4 and 8h. Aliquots were immediately frozen at −80°C for further analysis.…”

Estrogens and the regulation of glucose metabolism

“…Treatment with E2 decreases obesity[ 276 ], protects against hepatic steatosis[ 277 ], lowers the activity of cholesterol acyl-transferase[ 278 ] and limits fat deposition[ 279 ]. All these are –again– indirect actions aimed to decrease the storage of excess TAG, since E2 does not directly regulate lipolysis[ 280 ]. Nevertheless, estrogens decrease lipogenesis[ 281 ] in WAT; and adipogenesis is also inhibited through ERα activation[ 282 ].…”

Immunometabolic Links between Estrogen, Adipose Tissue and Female Reproductive Metabolism

“…In addition to suppressing lipogenesis and lipogenic gene expression (i.e., inhibiting adipogenesis), estrogen is reported to promote both basal and catecholamine-induced lipolysis [37], with a reduction in lipoprotein lipase activity observed in women with low estrogen levels [13]. However, this contrasts with a recent study using pair-fed OVX versus OVX + estrogen supplemented groups and surgical controls, which found no effect of estrogen on lipolysis in either visceral or subcutaneous depots by a number of different measures [38]. When considering the potential role of estrogen in metabolic flexibility of white adipose tissue, it is clear that additional context-dependent variables remain to be fully addressed.…”