Prolonged treatment with the β3-adrenergic agonist CL 316243 induces adipose tissue remodeling in rat but not in guinea pig: 2) modulation of glucose uptake and monoamine oxidase activity

Abstract

Beta3-adrenergic agonists are well-recognited to promote lipid mobilisation and adipose tissue remodeling in rodents, leading to multilocular fat cells enriched in mitochondria. However, effects of beta3-adrenergic agonists on glucose transport are still controversial. In this work, we studied in white adipose tissue (WAT) the influence of sustained beta3-adrenergic stimulation on the glucose transport and on the mitochondrial monoamine oxidase (MAO) activity. As one-week administration of CL 316243 (CL, 1 mg/kg/d) induces beta-adrenergic desensitization in rat but not in guinea pig adipocytes, attention was paid to compare these models. When expressing glucose uptake as nmoles of 2-deoxyglucose/100 mg cell lipids, maximally stimulated uptake was increased in adipocytes of WAT from treated rats but not from treated guinea pigs. However, basal hexose uptake was also increased in CL-treated rats and, as a consequence, the dose-dependent curves for insulin stimulation were similar in control and CL-treated rats when expressed as fold increase over basal. Insulin-induced lipogenesis was unchanged in rat or guinea pig adipocytes after CL-treatment. The glucose carriers GLUT4 and corresponding mRNA were increased in subcutaneous WAT or in brown adipose tissue (BAT) but not in visceral WAT or muscles of CL-treated rats. There was an increase of MAO activity in WAT and BAT, but not in liver, of CL-treated rats while no change was detected in guinea pigs. These findings show that only rat adipocytes, which are beta3-adrenergic-responsive, respond to chronic beta3-AR agonist by an increase of GLUT4 content and MAO activity, despite a desensitization of all beta-adrenoceptor subtypes.

Prolonged treatment with the β3-adrenergic agonist CL 316243 induces adipose tissue remodeling in rat but not in guinea pig: 1) fat store depletion and desensitization of β-adrenergic responses

“…Moreover, β 3 -adrenergic agonists have been shown to preserve loss of mus- cle protein (32). Unfortunately, we were unable to demonstrate any positive regulation of CL on the capacity of muscle to metabolize glucose in the second part of the present study (12).…”

Influence of prolonged fasting on monoamine oxidase and semicarbazide-sensitive amine oxidase activities in rat white adipose tissue

“…Moreover, the decrease of MAO expression observed in fastinginduced depletion could not be generalized to all the situations of lipid mobilization. For instance, visceral fat tissue of rats treated with a β3-adrenergic agonist exhibits a strong lipid mobilization (9) but also an increased mitochondriogenesis (12), and an increased MAO activity in the INWAT (8). Thus, factors playing a positive role on mitochondrial function can increase MAO activity in adipocytes, regardless of fat cell size.…”

“…The results were expressed as percentage of responses to 10 nM isoprenaline, which is independent of fat cell size and basal triglyceride breakdown (9). The previously described technique used for the determination of 2-deoxyglucose uptake into adipocytes (8) was adapted to small pieces of adipose tissues, incubated without previous collagenase digestion, and separation between internalized hexose from extracellular was performed by successive washings as for muscle (19) instead of the centrifugation through dynonylphtalate layer used for buoyant fat cells (8).…”

Lack of direct insulin-like action of visfatin/Nampt/PBEF1 in human adipocytes

“…For hexose uptake assays, incubations of the tested agents with fat cell suspensions lasted 45 min at 37 °C before 10 min exposure to 0.1 mM [ 3 H]-2-deoxyglucose (2-DG) as previously described (11). Separation between internalized hexose and extracellular form was performed on 200 μl aliquots by centrifugation through dynonyl-phtalate layer which allowed to separate buoyant intact fat cells from medium (5). Lipid content was determined as previously reported (1).…”

“…Lipid content was determined as previously reported (1). Uptake was expressed as nmol 2-DG internalized / 100 mg cellular lipids / 10 min or as fold increase over basal uptake (5).…”