Tomonobu Sakurai

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

The effect of exercise on β‐adrenergic receptor (β‐AR) trafficking was investigated in rat adipocytes. The binding sites of a hydrophilic ligand, [3H]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 β2‐AR proteins in membrane fractions. The protein expressions of both G‐protein‐coupled receptor kinase (GRK)‐2 and β‐arrestin‐2 were reduced, with a decline in β2‐AR ubiquitination at 0 h and 3 h. The protein expressions of β2‐AR, GRK‐2, β‐arrestin‐2, the β2‐AR/β‐arrestin‐2 complex, and β2‐AR ubiquitination returned to their respective control levels at 24 h, whereas the β2‐AR mRNA level was reduced. Administration of either lactacystin or propranolol did not alter GRK‐2 and β2‐AR protein expressions after exercise. Thus, the mechanism underlying the increased density of β2‐AR up to at least 3 h may involve alterations in a multistep event involving the coordinate interaction among proteins mediating β2‐AR trafficking, in which both the receptor‐agonist interactions and ubiquitin‐proteasome pathway have a key role. However, the decreased protein expression of β2‐AR at 24 h might be due to some change occurring at the translational levels.

Swimming training prevents generation of suppressor macrophages during acute cold stress.

PURPOSE Acute cold stress induces suppressor macrophages expressing large numbers of receptors to Fc portion of immunoglobulin G (MAC-1+ Fc gammaRII/IIIbright cells), resulting in suppression of splenocyte mitogenesis. The generation of MAC-1+ Fc gammaRII/IIIbright cells is partly mediated by increased glucocorticoid levels during acute cold stress. The aim of the current study was to investigate the effect of swimming training on the generation of the MAC-1+ Fc gammaRII/IIIbright suppressor macrophages by acute cold stress. METHODS The trained mice underwent a 6-wk endurance swimming training (5 times/wk) in water at 35-36 degrees C for 90 min. The swimming training significantly increased brown adipose tissue mass, suggesting improved cold tolerance. Actually, when the swimming-trained mice were exposed to 5 degrees C for 3 h (acute cold stress), the rectal temperature was not decreased. The proportion of MAC-1+ Fc gammaRII/IIIbright cells in peritoneal exudate cells from swimming-trained mice was significantly lower than that from control mice. In addition, the proportion of MAC-1+ Fc gammaRII/IIIbright cells in peritoneal exudate cell population from swimming-trained mice was unaffected by the acute cold stress. The swimming training significantly attenuated the increases in serum corticosterone levels in response to acute cold stress. These results suggested that swimming training not only improves cold tolerance but also inhibits the generation of suppressor macrophages under acute cold stress as well as under normal conditions.

The Molecular Mechanism Underlying Continuous Exercise Training-Induced Adaptive Changes of Lipolysis in White Adipose Cells

Physical exercise accelerates the mobilization of free fatty acids from white adipocytes to provide fuel for energy. This happens in several tissues and helps to regulate a whole-body state of metabolism. Under these conditions, the hydrolysis of triacylglycerol (TG) that is found in white adipocytes is known to be augmented via the activation of these lipolytic events, which is referred to as the “lipolytic cascade.” Indeed, evidence has shown that the lipolytic responses in white adipocytes are upregulated by continuous exercise training (ET) through the adaptive changes in molecules that constitute the lipolytic cascade. During the past few decades, many lipolysis-related molecules have been identified. Of note, the discovery of a new lipase, known as adipose triglyceride lipase, has redefined the existing concepts of the hormone-sensitive lipase-dependent hydrolysis of TG in white adipocytes. This review outlines the alterations in the lipolytic molecules of white adipocytes that result from ET, which includes the molecular regulation of TG lipases through the lipolytic cascade.

A single bout of exercise brings about capillary growth in skeletal muscle through basic fibroblast growth factor (bFGF)

Abstract The purpose of the present study was to investigate the effect of a single bout of exercise on the capillary growth in an in vitro angiogenesis model and its mechanism. The exercised rats were made to run continuously for 90 min at 20 m/min (0° incline) on a rodent treadmill just before sacrifice. First, we investigated the effect of soleus extracts on the capillary growth in an in vitro angiogenesis model based on the co-culture of rat interstitial cells (like smooth muscle cell) (RSMC) and bovine capillary endothelial cells (BCEC). The extracts of soleus muscle from acutely-exercised rats had higher angiogenic activity, compared with those from control rats. The expression of bFGF mRNA in soleus muscle from acutely-exercised rats was also significantly higher than in that from control rats. Next, we found that norepinephrine (NE) at the concentration of 10 −8 to 10 −5 M enhanced the capillary growth in the angiogenesis model. Furthermore, the addition of 10 −7 M NE markedly enhanced the expression of bFGF mRNA in RSMC, but not in BCEC. The data obtained here suggest that the increased level of NE with physical exercise upregulates the expression of bFGF in satellite cells like RSMC, probably leading to the increased capillarization in skeletal muscle.