Lipolytic catecholamine resistance due to decreased beta 2-adrenoceptor expression in fat cells.

Abstract

The existence of lipolytic f-adrenoceptor (BAR) resistance was investigated in vivo and in isolated abdominal subcutaneous adipocytes in 65 healthy and drug-free subjects. The concentration of isoprenaline (nonselective BAR agonist) causing half-maximum lipolysis effect (EDEo) varied bimodally and 10'-fold between individuals but was almost constant in the same subject when measured two times at rest or before and 30 min after exercise. The subjects were categorized as having either high or low isoprenaline sensitivity. The former group had a 50% reduced in vivo lipolytic response to exercise and mental stress, despite a 50% increased plasma noradrenaline response (P < 0.01) and a 350% increased plasma adrenaline response (P < 0.02). In fat cells the lipolytic ED59 values for noradrenaline and terbutaline (BAR2 agonist) were 10 times lower (P < 0.001) in low-sensitive subjects, but the maximum lipolytic actions ofthese agents (and ofisoprenaline) were similar in both groups. The action on lipolysis of dobutamine (BAR1 agonist), forskolin (stimulating adenylate cyclase), dibuturyl cyclic AMP (activating protein kinase), clonidine (a2-adrenergic agonist), or phenyl isopropyladenosine (adenosine receptor agonist) were almost identical in high-and low-sensitivity subjects. ED5, for isoprenaline correlated with ED5, for terbutaline (r = 0.75), but not with ED5o for dobutamine. In high-sensitivity subjects the number of BAR2 was almost threefold increased (P < 0.002) and the steady-state adipocyte mRNA level for BAR2 was sixfold increased (P < 0.005).BAR2 affinity as well as BAR, number, affinity and mRNA expression were similar in both groups. In 11 cholecystectomy patients (otherwise healthy) lipolytic ED5o for 0 agonists correlated in omental and subcutaneous fat cells (r = 0.85 for isoprenaline; r = 0.95 for terbutaline). In conclusion, lipolytic resistance to catecholamines is present in vivo in apparently healthy subjects due to reduced expression of BAR2 in adipocytes. (J. Clin. Invest. 1992. 90:2175-2186

Lipolytic catecholamine resistance linked to α2-adrenoceptor sensitivity—a metabolic predictor of weight loss in obese subjects

“…11 Fat cell diameter, weight and volume as well as the number of fat cells incubated were determined as described. 12 The lipolysis assay has previously been described in detail. 12 Brie¯y, a diluted suspension of fat cells (about 5±10 000 cells/ml) was incubated in duplicate, with air as the gas phase, for 2 h at 37 C in Krebs± Ringer phosphate buffer (pH 7.4) supplemented with glucose (1 mg/ml), ascorbic acid (0.1 mg/ml) and bovine serum albumin (20 mg/ml) in the absence (basal) or presence of increasing concentrations of different lipolytic and antilipolytic agents.…”

“…12 The lipolysis assay has previously been described in detail. 12 Brie¯y, a diluted suspension of fat cells (about 5±10 000 cells/ml) was incubated in duplicate, with air as the gas phase, for 2 h at 37 C in Krebs± Ringer phosphate buffer (pH 7.4) supplemented with glucose (1 mg/ml), ascorbic acid (0.1 mg/ml) and bovine serum albumin (20 mg/ml) in the absence (basal) or presence of increasing concentrations of different lipolytic and antilipolytic agents. We used the non-selective, natural catecholamine, noradrenaline, which acts on all three b-adrenoceptor subtypes and the a 2 -adrenoceptor, the b 2 -adrenoceptor-selective agonist terbutaline and the b 1 -adrenoceptor-selective agonist dobutamine.…”

“…In the diluted fat cell suspension presently used, there is no in¯uence of traces of adenosine on the effect of agents that stimulate lipolysis as discussed. 12 After incubation, an aliquot of the medium was removed and glycerol (lipolytic index) was analyzed using a bioluminescence method. 13 All the agonists caused a dose-dependent increase or inhibition of glycerol release, reaching a plateau at the highest agonist concentrations.…”

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…Lipogenesis can also be studied after a pulse with 3 H 2 O and lipid extraction (237). Lipolysis is also studied by measuring catecholamine-stimulated glycerol release (645)(646)(647).…”

DNA Polymorphisms in the α2‐ and β2 Adrenoceptor Genes and Regional Fat Distribution in Humans: Association and Linkage Studies

“…Interestingly, evidence for lipolytic catecholamine resistance was recently reported in healthy subjects and was apparently mainly due to reduced expression of P2-AR in adipocytes (30).…”