Maintenance of skeletal muscle mass relies on the dynamic balance between anabolic and catabolic processes and is important for motility, systemic energy homeostasis, and viability. We identified direct target genes of the glucocorticoid receptor (GR) in skeletal muscle, i.e., REDD1 and KLF15. As well as REDD1, KLF15 inhibits mTOR activity, but via a distinct mechanism involving BCAT2 gene activation. Moreover, KLF15 upregulates the expression of the E3 ubiquitin ligases atrogin-1 and MuRF1 genes and negatively modulates myofiber size. Thus, GR is a liaison involving a variety of downstream molecular cascades toward muscle atrophy. Notably, mTOR activation inhibits GR transcription function and efficiently counteracts the catabolic processes provoked by glucocorticoids. This mutually exclusive crosstalk between GR and mTOR, a highly coordinated interaction between the catabolic hormone signal and the anabolic machinery, may be a rational mechanism for fine-tuning of muscle volume and a potential therapeutic target for muscle wasting.

Tea catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG), have been shown to be epimerized to (-)-catechin (C), (-)-gallocatechin (GC), (-)-catechin gallate (CG), and (-)-gallocatechin gallate (GCG), respectively, during heat treatment. In this study, we examined the effect of tea catechins rich in ECG and EGCG and heat-treated tea catechins rich in CG and GCG on postprandial hypertriacylglycerolemia in rats. Both tea catechins and heat-treated tea catechins suppressed postprandial hypertriacylglycerolemia. Lymphatic recovery of (14)C-trioleoylglycerol in rats cannulated in the thoracic duct was delayed by the administration of tea catechins and heat-treated tea catechins. Tea catechins and heat-treated tea catechins had the same effect on all variables tested. These catechin preparations dose-dependently inhibited the activity of pancreatic lipase in vitro. When purified catechins were used, only those with a galloyl moiety inhibited the activity of pancreatic lipase. These results suggest that catechins with a galloyl moiety suppress postprandial hypertriacylglycerolemia by slowing down triacylglycerol absorption through the inhibition of pancreatic lipase. Because postprandial hypertriacylglycerolemia is a risk factor for coronary heart disease, our results suggest that catechins with a galloyl moiety may prevent this disease.

Macrophages are known to be phagocytes in the olfactory epithelium of adult rats. The participation of other cell types in phagocytosis in association with the cell death process was examined in the olfactory epithelium after unilateral bulbectomy of neonatal mice. The terminal deoxynucleotidyl transferase (TdT)-mediated biotinylated dUTP nick end-labeling (TUNEL) method revealed that the process of olfactory cell death consists of acute and chronic periods. The number of apoptotic cell profiles on the operated side peaked at 1 day, and the percentage of labeled cell profiles was 13.6%. The number of dying cells rapidly decreased at 3 days and decreased further at 5 days. Only 3% of the cells were labeled at 5 days. The percentage of dying cells increased again at the end of first postoperative week and remained two- to four-fold higher than control values for 2 months (4.7-5.3%). Electron micrographs of sections from early postbulbectomy stages (1-7 days) showed that as many as 30% of supporting cell profiles contained apoptotic bodies, cellular debris and phagosomes in the cytoplasm. The number of supporting cell profiles containing phagosomes declined to a plateau 2 weeks following bulbectomy and remained at 8-12% of the supporting cell population for 2 months. The results indicate that supporting cells in the olfactory epithelium play a significant role in phagocytosis in both acute and chronic of cell death after bulbectomy in newborn mice. However, supporting cells are not the exclusive phagocytic cell type in the bulbectomized epithelium; a small number of macrophages was also observed. Moreover, the phagocytosis by supporting cells was observed in unperturbed epithelium in the early stages during postnatal development.

SummaryThe fibrinolytic system dissolves fibrin and maintains vascular patency. Recent advances in imaging analyses allowed visualization of the spatiotemporal regulatory mechanism of fibrinolysis, as well as its regulation by other plasma hemostasis cofactors. Vascular endothelial cells (VECs) retain tissue‐type plasminogen activator (tPA) after secretion and maintain high plasminogen (plg) activation potential on their surfaces. As in plasma, the serpin, plasminogen activator inhibitor type 1 (PAI‐1), regulates fibrinolytic potential via inhibition of the VEC surface‐bound plg activator, tPA. Once fibrin is formed, plg activation by tPA is initiated and effectively amplified on the surface of fibrin, and fibrin is rapidly degraded. The specific binding of plg and tPA to lytic edges of partly degraded fibrin via newly generated C‐terminal lysine residues, which amplifies fibrin digestion, is a central aspect of this pathophysiological mechanism. Thrombomodulin (TM) plays a role in the attenuation of plg binding on fibrin and the associated fibrinolysis, which is reversed by a carboxypeptidase B inhibitor. This suggests that the plasma procarboxypeptidase B, thrombin‐activatable fibrinolysis inhibitor (TAFI), which is activated by thrombin bound to TM on VECs, is a critical aspect of the regulation of plg activation on VECs and subsequent fibrinolysis. Platelets also contain PAI‐1, TAFI, TM, and the fibrin cross‐linking enzyme, factor (F) XIIIa, and either secrete or expose these agents upon activation in order to regulate fibrinolysis. In this review, the native machinery of plg activation and fibrinolysis, as well as their spatiotemporal regulatory mechanisms, as revealed by imaging analyses, are discussed.

No abstract

The metabolism of theanine, one of the major amino acid components in tea (Camellia sinensis), was studied in rats. High-performance liquid chromatography (HPLC) with fluorometric detection was used to evaluate the nature of theanine's metabolites in plasma, urine, and tissues. In the urine samples collected after administration of 100, 200, and 400 mg each of theanine, intact theanine, L-glutamic acid, and ethylamine, these compounds were detected in a dose-dependent manner. When 200 mg of theanine was orally administered to rats, the plasma concentrations of theanine and ethylamine reached their highest levels about 0.5 and 2 h after administration, respectively. It seems most likely that the enzymatic hydrolysis of theanine to glutamic acid and ethylamine was accomplished in the kidney. These results indicate that orally administered theanine is absorbed through the intestinal tract and hydrolyzed to glutamic acid and ethylamine in the rat kidney.

We investigated the effect of consumption of a catechin-containing drink on body fat level and its safety in healthy adults. The beverage (250 ml/bottle) contained 215.3 mg of tea catechins mostly possessing a galloyl moiety, which included (-)-epigallocatechin gallate 74.6 mg, (-)-epicatechin gallate 34.1 mg, (-)-gallocatechin gallate 77.8 mg, (-)-catechin gallate 24.5 mg. We conducted a double-blind study with three parallel groups. Healthy subjects (98 men and 97 women) aged from 20 to 65 years old with 22.5 < body mass index (BMI) ≤ 30 kg/m 2 were assigned to consume 3 bottles of placebo drink (control group), 2 bottles of catechin-containing drink and 1 bottle of placebo drink (low-dose group), or 3 bottles of catechin-containing drink (high-dose group), per day at mealtimes for 12 week (daily consumption of catechins was 41.1, 444.3 or 665.9 mg respectively). Compared to the value at 0 week, consumption of two or three bottles of catechin-containing drink results in significant decrease in body weight and BMI at 8 and 12 or 4, 8 and 12 week, respectively. Body weight and BMI was significantly decreased in both catechin groups compared with the control group from 4 to 12 week. The measurements of abdominal fat areas indicated significant reduction of total fat area and visceral fat area in both catechin groups compared with the control group at 12 week. Thus our present observations suggest that consumption of a catechin-containing drink may be useful for the prevention of obesity-related disorders.

Although the stimulatory effect of glucagon-like peptide 1 (GLP-1), a cAMP-generating agonist, on Ca 2؉ signal and insulin secretion is well established, the underlying mechanisms remain to be fully elucidated. We recently discovered that Ca