β‐Adrenergic receptor trafficking by exercise in rat adipocytes: roles of G‐protein‐coupled receptor kinase‐2, β‐arrestin‐2, and the ubiquitin‐proteasome pathway

Abstract

The effect of exercise on beta-adrenergic receptor (beta-AR) trafficking was investigated in rat adipocytes. The binding sites of a hydrophilic ligand, [(3)H]CGP12177, increased immediately (0 h) and at 3 h after exercise (3 h) but decreased at 24 h after exercise (24 h). The data of immunoblotting revealed that the alterations in the binding sites mainly paralleled the alterations in the beta2-AR proteins in membrane fractions. The protein expressions of both G-protein-coupled receptor kinase (GRK)-2 and beta-arrestin-2 were reduced, with a decline in beta2-AR ubiquitination at 0 h and 3 h. The protein expressions of beta2-AR, GRK-2, beta-arrestin-2, the beta2-AR/beta-arrestin-2 complex, and beta2-AR ubiquitination returned to their respective control levels at 24 h, whereas the beta2-AR mRNA level was reduced. Administration of either lactacystin or propranolol did not alter GRK-2 and beta2-AR protein expressions after exercise. Thus, the mechanism underlying the increased density of beta2-AR up to at least 3 h may involve alterations in a multistep event involving the coordinate interaction among proteins mediating beta2-AR trafficking, in which both the receptor-agonist interactions and ubiquitin-proteasome pathway have a key role. However, the decreased protein expression of beta2-AR at 24 h might be due to some change occurring at the translational levels.

Beta-arrestin inhibits CAMKKbeta-dependent AMPK activation downstream of protease-activated-receptor-2

“…There is increasing evidence that obesity can be viewed as an inflammatory disorder, associated with increased circulating inflammatory cytokines and macrophage infiltration into fat, which in turn exacerbates defects associated with Type 2 Diabetes. PAR 2 has been implicated in numerous inflammatory pathways and there is some evidence that β-arrestin levels can be altered under different physiological conditions [37,38] and in a mouse model of insulin resistance (db/db mice)[39]. β-arrestins have also been reported to contribute to insulin resistance by mediating a TNFα-induced inflammatory pathway[40].…”

Higher Levels of ATGL Are Associated with Exercise-Induced Enhancement of Lipolysis in Rat Epididymal Adipocytes

“…RNA extraction and RT-PCR analysis of mRNAs for ATGL and PPARg-2 and b-actin were performed using an RT-PCR system, as previously described [47], [48]. Twenty-five cycles of amplification were carried out for ATGL and PPARg-2 mRNAs, and 20 cycles were used for b-actin mRNA.…”

Muscle Plasticity and β2‐Adrenergic Receptors: Adaptive Responses of β2‐Adrenergic Receptor Expression to Muscle Hypertrophy and Atrophy

“…Nevertheless, there is little information on the response of β 2 -AR expression to exercise training in skeletal muscles. However, many studies demonstrate the effects of exercise training on β 2 -AR expression in several tissues and cell types such as myocardia [73, 74], adipocytes [75], and macrophages [76]. Barbier et al [73] demonstrated that exercise training induces changes in the distribution of β 1 -, β 2 -, and β 3 -AR densities in the rat left ventricle.…”

“…Barbier et al [73] demonstrated that exercise training induces changes in the distribution of β 1 -, β 2 -, and β 3 -AR densities in the rat left ventricle. In adipocytes, the exercise-induced trafficking of β 2 -AR into the cell membrane from the cytosol is coupled with adipocytes' function to increase intracellular cAMP production [75]. Kizaki et al [76] also found a reduction in the expression of β 2 -AR mRNA in macrophages and highlight the significance of β 2 -AR in the exercise training-induced improvement of macrophages' innate immune function.…”