Pregnancy modifies the α2-β-adrenergic receptor functional balance in rabbit fat cells (original) (raw)
Related papers
Pregnancy modifies the ␣ 2-  -adrenergic receptor functional balance in rabbit fat cells
The Journal of Lipid Research
The sympathetic nervous system controls lipolysis in fat by activation of four adrenergic receptors:  1,  2,  3, and ␣ 2. During pregnancy, maternal metabolism presents anabolic and catabolic phases, characterized by modifications of fat responsiveness to catecholamines. The contributions of the four adrenergic receptors to adipocyte responsiveness during pregnancy have never been studied. Our aim was to evaluate the influence of pregnancy on adrenergic receptor-mediated lipolysis in rabbit white adipocytes. Functional studies were performed using subtypeselective and non-selective adrenergic receptor agonists. Overall adrenergic responsiveness was measured with the physiological agonist epinephrine. Non-adrenergic agents were used to evaluate different steps of the lipolytic cascade. The ␣ 2-and  1/  2-adrenergic receptor numbers were determined with selective radioligands. Non-adrenergic agents revealed that pregnancy induced an intracytoplasmic modification of the lipolytic cascade in inguinal but not in retroperitoneal adipocytes. Pregnancy induced an increase in  1-and specially  3-mediated lipolysis. The amounts of adipocyte  1/  2-and ␣ 2-adrenergic receptors were increased in pregnant rabbits. Epinephrine effects revealed an increased contribution of ␣ 2-adrenergic receptor-mediated antilipolysis in adipocytes from pregnant rabbits. These results indicate that pregnancy regulates adipocyte responsiveness to catecholamines mainly via the ␣ 2-and  3-adrenergic pathways. Pregnancy induces an intracytoplasmic modification of the lipolytic cascade, probably via hormone-sensitive lipase, with differences according to fat location.-Bousquet-Mélou, A
Pregnancy Effects on Rat Adipose Tissue Lipolytic Capacity are Dependent on Anatomical Location
Cellular Physiology and Biochemistry, 2005
Pregnancy is characterized by changes in maternal adiposity. The aim of this study was to carry out a detailed analysis of the different steps of the adrenergic pathway, lipoprotein lipase (LPL) levels and adipocyte size, in order to evaluate the response of white adipose tissue (WAT) to the metabolic changes during pregnancy depending on the anatomical location. In general, the levels of the proteins of the lipolytic pathway decreased with pregnancy. In retroperitoneal WAT adenylate cyclase (AC) levels decreased from 100% in controls to 44% by day 13 and 11% by day 20. In mesenteric WAT the α 2A /β 3-adrenergic receptor balance seemed to be one of the main regulatory points of the lipolytic pathway and the reduction in the postreceptor element levels was clearly lower than for the other two depots (PKA levels reduced from 100% in controls to 72% by day 20, while in the other two depots it decreased to 30%, and AC and HSL levels did not show statistically significant changes in this depot). In contrast, the LPL-to-HSL ratio may be a major regulatory point in gonadal WAT. In summary, we describe regional differences in the regulation of WAT metabolism throughout pregnancy, which may be of great importance to determine the role of the different fat depots during late pregnancy. Thus, gonadal and mesenteric WAT changed to a lipolytic state to sustain the rapid foetal growth, although with differences between them in the main regulatory points, while retroperitoneal WAT could have a role later on, during lactation.
2010
Placental insufficiency-induced intrauterine growth restriction (IUGR) fetuses have chronic hypoxaemia and elevated plasma catecholamine concentrations. In this study, we determined whether adrenergic responsiveness becomes desensitized in the perirenal adipose tissue of IUGR fetuses and lambs by measuring adrenergic receptor (AR) mRNA and protein levels. We also tested the ability of adrenaline to mobilize non-esterified fatty acids (NEFAs) in young lambs. Perirenal adipose tissue was collected from IUGR and control fetuses at 133 days of gestational age (dGA) and lambs at 18 days of age (dA). β 2 -AR mRNA concentrations were 59% and 74% lower (P < 0.05) in IUGR fetuses and lambs compared to controls, respectively, which also resulted in lower protein levels (P < 0.05). No treatment differences were detected for α 1A -, α 1B -, α 1D -, α 2A -, α 2B -, α 2C -, β 1 -and β 3 -AR expression. mRNA concentrations were also determined for hormone sensitive lipase (HSL), perilipin (lipid droplet-associated protein), and two adipokines, leptin and adiponectin. Adiponectin and HSL were not different between treatments at either age. Compared to controls, perilipin and leptin mRNA concentrations were lower (P < 0.05) in IUGR fetuses but not in lambs. Because of the β 2 -AR results, we challenged a second cohort of lambs with exogenous adrenaline at 21 dA. The ability of adrenaline to mobilize NEFA was 55 ± 15% lower (P < 0.05) in IUGRs than controls. Collectively, our findings indicate that elevated catecholamine exposure in utero causes desensitization of adipose tissue by down-regulation of β 2 -AR, and this persists in lambs. This impairment in adrenergic stimulated lipolysis might partially explain early onset obesity in IUGR offspring.
Adrenergic regulation of adipocyte metabolism
Five adrenoceptor (AR) subtypes (Pi, P 2 , 03> oc 2 and oti), are involved in the control of white and brown fat cell function. A number of metabolic events are controlled by the adrenergic system in fat cells. The stimulatory effect of catecholamines on lipolysis and metabolism is mainly connected to increments in cAMP levels, cAMP protein kinase activation and phosphorylation of various target proteins. Norepinephrine and epinephrine operate through differential recruitment of o^-and p*-AR subtypes on the basis of their relative affinity for the different subtypes (the relative order of affinity is (X2 > Pi 22 |3 2 > P3 for norepinephrine). Antagonistic actions at the level of cAMP production exist between 0C2-and p r , p 2 -and p 3 -AR-mediated lipolytic effects in human white fat cells. The role of fat cell (X2-ARs, which largely outnumber p-ARs in fat cells of certain fat deposits, in human and primate has never been clearly understood. The other AR type which is not linked to lipolysis regulation, the oc r AR, is involved in the control of glycogenolysis and lactate production. Pharmacological approaches using in-situ microdialysis and selective oc 2 -and P-AR agonists and antagonists have revealed sex-and tissue-specific differences in the adrenergic control of fat cell function and nutritive blood flow in the tissue surrounding the microdialysis probe.
Circulating metabolite utilization by periuterine adipose tissue in situ in the pregnant rat
Metabolism, 1991
To study the use of glucose for lipid synthesis by the periuterine adipose tissue in situ, "C-glucose was infused through the left uterine artery of anesthetized, fed pregnant and virgin control rats. A greater amount of "C-lipid always appeared in the adipose tissue from the left uterine horn than in the tissue from the right uterine horn, indicating direct utilization of the infused "C-glucose by the tissue. Glucose utilization for both glyceride glycerol and fatty acid synthesis increased from day 0 (virgin rats) to day 20 of gestation and then decreased dramatically on day 21. In virgin and 12-day pregnant rats, glucose was incorporated into either lipidic moiety at similar rates, whereas in late pregnant rats glucose utilization for glyceride glycerol synthesis was four to five times greater than for fatty acids. The utilization of circulating fatty acids and the lipoprotein triglyceride-derived fatty acids was studied by infusing %palmitate or "C-triolein-labeled very-low-density lipoprotein (VLDL) through the left uterine artery in both virgin and 20-day pregnant rats. Incorporation of fatty acids from either one of these plasma sources was significantly higher in the pregnant than in virgin rats. This high amount of fatty acid acquisition did not account for the very active glyceride glycerol synthesis observed in pregnant rats and can only be explained by the intracellular reesterification of some lipolitic fatty acids. The results suggest a highly accelerated triacylglycerol/fatty acid substrate cycle in adipose tissue during late pregnancy, which would allow active esterification (contributing to fat accumulation) and responsive lipolysis (permitting rapid fat mobilization) by the mother.
American Journal of Physiology-endocrinology and Metabolism, 1994
To investigate the factors controlling maternal depot fat accumulation during early pregnancy and net decrease during late pregnancy, the activity and mRNA expression of adipose tissue lipoprotein lipase (LPL) and hormonesensitive lipase (HSL) were related to several other lipid metabolic parameters. Virgin control rats, pregnant rats (at days 12, 15, 19, and 21), and lactating rats (at days 5 and 10 postpartum) were studied.
Biochemical and Biophysical Research Communications, 1981
To determine whether the reduced lipoprotein lipase activity in adipose tissue in late pregnancy corresponds to parallel changes in the uptake of triglyceride fatty acids, isolated adipocytes from 19-and 21-day pregnant rats and virgin controls were incubated for different periods in the presence of rat plasma triglyceride-rich lipoproteins with their esterified fatty acids of neutral glycerides (triglycerides) labelled with 3H. The hydrolysis of triglycerides and uptake of fatty acids by the adipocytes increased linearly and parabolically with respect to the incubation time and were always lower in cells from pregnant animals than from controls. Addition of heparin to the incubation medium produced similar increases in hydrolysis and uptake in all groups. Results indicate that the diminished uptake of triglyceride fatty acids by adipose tissue contributes to hypertriglyceridemia in late pregnancy which is counteracted by lipogenesis increase tc maintain the mother's augmented body fat.
Annals of the New York Academy of Sciences, 1998
In the adipose tissue, the β-adrenergic receptors are involved in the activation of lipolysis by catecholamines. At present, three types of β-adrenoceptor (β-AR), namely, the β 1 -, β 2 -, and β 3 -AR, are characterized by their distinct pharmacological properties, protein sequence and gene organization. In the 1980s, the β 3 -AR agonists were claimed to be potential antiobesity drugs because of their strong lipolytic capacity and slimming effects observed in rodents. 2 However, 10 years later, none of such agents is actually prescribed in obesity therapy. The following observation can a posteriori explain this fact: the three types of β-ARs are present and functional in rat fat cells, whereas the presence of a functional β 3 -AR in human adipocytes is still controversial. 3 This discrepancy is not surprising, because in earlier studies the adrenergic regulation of rat adipocyte metabolism was not entirely predictive of that of human adipocytes. 4 A comparative study was undertaken in order to further understand these species-specific differences and to define a more useful model of the human adipocyte.