Cinnamtannin A2, (-)-epicatechin tetramer, attenuates skeletal muscle wasting in disuse atrophy model mice induced by hindlimb suspension.

The impact of repeated administration of cinntamtannin A2 (A2, 25 µg/kg) on skeletal muscle disuse atrophy model mice induced by hindlimb suspension for 14 days was examined. In soleus, weight loss and a reduction in the average myofibre size with shifting to the smaller side of the peak were observed in the suspension-vehicle group, but A2 reduced these changes. Average myofibre size significantly increased in ground-A2 compared to ground-vehicle. A marked increase in the dephosphorylation of forkhead box O (FoxO) 3a by the suspension was reduced by A2. The phosphorylation of protein kinase B (Akt) and eukaryotic translation initiation factor 4E-binding protein (4EBP)-1 were significantly increased by the treatment of A2. In addition, a single dose of A2 increased dramatically in the 24-h excretion of catecholamines in urine. These results suggest that A2 administration results in sympathetic nerve activation and promotes hypertrophy while inhibiting the progress of disuse muscle atrophy.

Difference in endocrine and behavior between short-term single- and paired-housing mice in metabolic cage.

Metabolic cage housing which is exposed to a number of environmental stressors is often used in pharmacokinetic studies. In this study, we compared the difference in stress response between single- and paired-housing in metabolic cages by evaluating the alteration of urinary stress hormones and behavior. Mice were randomly divided into single- or paired-housing groups and placed in a metabolic cage with wire mesh. Their urine was collected every 24 h for consecutive 4 days to determine excreted catecholamine and corticosterone. The change in body weight was significantly decreased at 3 and 4 days in the single-housing group compared with that before the experiment, but not paired-housing group. The level of urinary catecholamines, such as noradrenaline, adrenaline, and their metabolite vanillylmandelic acid, was significantly increased in the single-housing compared with paired housing group and urinary corticosterone increased as well. Next, for the two similarly housed groups, we observed spontaneous behavior on the fourth day and conducted an elevated plus-maze test on the fifth day. Spontaneous behavior was not different between experimental groups. In the elevated plus-maze test, the proportion of time spent in the open arms was significantly prolonged in the paired-housing group compared to that of the single-housing group. Short-term social isolation stress loading in metabolic cages was suggested to exhibit endocrinological and behavioral changes in mice. To reduce such interference due to stress exposure, it was suggested to keep two mice in a metabolic cage.

Repeated Oral Administration of Flavan-3-ols Induces Browning in Mice Adipose Tissues through Sympathetic Nerve Activation.

We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ol (FL)s, a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FLs possibly activate sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FLs. In addition, we examined the impact of the repeated administration of 50 mg/kg FLs for 14 days on adipose tissues in mice. In BAT, FLs tended to increase the level of Ucp-1 along with significant increase of thermogenic transcriptome factors expressions, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Expression of browning markers, CD137 and transmembrane protein (TMEM) 26, in addition to PGC-1α were increased in epididymal adipose (eWAT) by FLs. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 by FLs. These results exert that FLs induce browning in adipose, and this change is possibly produced by the activation of the SNS.