Acute modulation of adipose tissue lipolysis by intravenous estrogens

Abstract

Objective: The aim of this study was to determine whether intravenous (IV) conjugated estrogens (EST) acutely enhance the suppression of whole-body or regional subcutaneous adipose tissue (SAT) lipolysis by insulin in postmenopausal women.

Research methods and procedures: We assessed whole-body lipolysis by [(2)H(5)]glycerol rate of appearance (Glyc(RA)) and abdominal and femoral SAT lipolysis (interstitial glycerol; Glyc(IS)) by subcutaneous microdialysis. Postmenopausal women (n = 12) were studied on two occasions, with IV EST or saline control (CON), under basal conditions and during a 3-stage (4, 8, and 40 mU/m(2)/min) hyperinsulinemic, euglycemic clamp. Ethanol outflow/inflow ratio and recovery of [(13)C]glycerol during microdialysis were used to assess blood flow changes and interstitial glycerol concentrations, respectively.

Results: Compared with CON, EST did not affect systemic basal or insulin-mediated suppression of lipolysis (Glyc(RA)) or SAT nutritive blood flow. Basal Glyc(IS) in SAT was reduced on the EST day. However, insulin-mediated suppression of lipolysis in SAT was not significantly influenced by EST.

Discussion: These findings suggest that estrogens acutely reduce basal lipolysis in SAT through an unknown mechanism but do not alter whole-body or SAT suppression of lipolysis by insulin.

Figures

Figure 1

Illustration of the 3-stage hyperinsulinemic, euglycemic clamp protocol. IIR, insulin infusion rate; GIR, glucose infusion rate. Blood samples were obtained at time 0 and at the 60, 75, and 90 min time-points during the basal period and stages 1 (4 mU/m2/min), 2 (8 mU/m2/min), and 3 (40 mU/m2/min). Conjugated estrogens (CE) were given as an IV bolus (2.5 mg) after the fasting blood samples (time 0) on one of the two (randomly determined) testing days.

Figure 2

Mean (± standard error; n = 12) serum estradiol and estrone concentrations on the EST day at time 0 (before IV conjugated estrogen bolus) and during the basal period and each stage of the hyperinsulinemic, euglycemic clamp.

Figure 3

Mean (± standard error) serum glycerol concentrations (n = 12; top panel) and GlycRA (n = 10, bottom panel) during the basal period and each stage of the hyperinsulinemic, euglycemic clamp on the estrogen day (EST) compared with the control day (CON). There was a significant (p < 0.005) main effect of insulin stage, but not treatment day, on glycerol concentrations and Ra.

Figure 4

Mean (± standard error; n = 12) femoral and abdominal subcutaneous adipose tissue nutritive blood flow (ethanol outflow/inflow ratio) throughout the hyperinsulinemic, euglycemic clamp on the estrogen day (EST) compared with the control day (CON).

Figure 5

Mean (± standard error; n = 12) femoral and abdominal subcutaneous adipose tissue interstitial glycerol concentrations throughout the hyperinsulinemic, euglycemic clamp on the estrogen day (EST) compared with the control day (CON). There were significant main effects of: 1) insulin stage (p < 0.001); 2) treatment day (p < 0.05, EST<CON); and 3) fat region (p = 0.001, abdominal<femoral) on interstitial glycerol concentrations.