In Vivo α₁-Adrenergic Lipolytic Activity in Subcutaneous Adipose Tissue of Obese Subjects

Abstract

The role of ␣ 1 -adrenoceptors in lipid mobilization and blood flow was investigated in situ using microdialysis of subcutaneous adipose tissue in severely obese subjects. The lipolysis rate was assessed by determination of interstitial glycerol concentration. The ␣ 1 -adrenoceptor agonist norfenefrine caused an increase in glycerol level in adipose tissue that was similar to that observed with the physiologic ␣ 1,2 -␤ 1 -adrenoceptor agonist norepinephrine, whereas the ␣ 1 -adrenoceptor antagonist urapidil showed no effect on basal lipolysis rate. However, the enhanced glycerol concentration due to norfenefrine and norepinephrine was suppressed in the presence of urapidil. The ␤-adrenoceptor antagonist propranolol showed no effect on norfenefrine-stimulated glycerol outflow. Blood flow was assessed using the ethanol escape technique. Perfusion with norfenefrine decreased blood flow, whereas urapidil enhanced blood flow significantly. Despite the increase in blood flow, the basal interstitial glycerol concentration remained unchanged. Although norfenefrine at high concentrations could inhibit the urapidil-induced increase in blood flow, the norfenefrine-induced glycerol output was not affected. These results demonstrate that ␣ 1 -adrenoceptors are involved in regulation of lipolysis rate and microcirculation of adipose tissue. However, the observed changes in local blood flow were not related to glycerol output.

ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics

“…Exposure of human white fat cells to the ADRA1 agonists norfenefrine and noradrenaline increased the glycerol concentration in the abdominal dialysate, showing that ADRA1 receptors are involved in the regulation of lipolysis rate and microcirculation of adipose tissue. 63 The evidence of a female gender effect on the ADRA1A gene in BMI in this study supports the existence of an antipsychotic and weight-gain effect through ADRA1A receptor antagonism, possibly regulated by female sex hormones. The implication of this study is limited by the fact that the research subjects were chronic schizophrenia who had been treated for many years that the antipsychotics-induced weight changes are less obvious than the schizophrenia subjects who were treated for the first time (for example, see Flechtner-Mors et al 63 ).…”

“…63 The evidence of a female gender effect on the ADRA1A gene in BMI in this study supports the existence of an antipsychotic and weight-gain effect through ADRA1A receptor antagonism, possibly regulated by female sex hormones. The implication of this study is limited by the fact that the research subjects were chronic schizophrenia who had been treated for many years that the antipsychotics-induced weight changes are less obvious than the schizophrenia subjects who were treated for the first time (for example, see Flechtner-Mors et al 63 ). The sensitivity for detecting a true association is thus reduced.…”

Update on adipose tissue blood flow regulation

“…Experiments using ␣-adrenergic stimuli, such as clonidine (66) and norfenefrine (57), confirmed the predominantly inhibitory effect of ␣-adrenoceptors on ATBF. Comparison of various agonists and antagonists showed that ␣ 2 -adrenoreceptor activation leads to more pronounced vasoconstriction, with little importance of ␣ 1 -receptors in AT microcirculation (11).…”

Recent evidence and potential mechanisms underlying weight gain and insulin resistance due to atypical antipsychotics

“…88 Some AAPs displayed higher affinity for adrenoreceptors a1 A/B and a2 A/B , specifically CLZ and RIS 9 , which are negatively correlated with lipolysis rate and body weight. Flechtner et al 91 assessed adipose tissue of severely obese subjects and identified that adrenoreceptors a1 are involved in regulation of lipolysis rate and microcirculation of adipose tissue. Also, pharmacological stimulation of the adrenergic system has been reported to reduce OL-induced weight gain.…”