Transmembrane G protein-coupled receptor 5 signaling stimulates fibroblast growth factor 21 expression concomitant with up-regulation of the transcription factor nuclear receptor Nr4a1.

Fibroblast growth factor 21 (FGF21) acts as an endocrine factor, playing important roles in the regulation of energy homeostasis, glucose and lipid metabolism. It is induced by diverse metabolic and cellular stresses, such as starvation and cold challenge, which in turn facilitate adaptation to the stress environment. The pharmacological action of FGF21 has received much attention, because the administration of FGF21 or its analogs has been shown to have an anti-obesity effect in rodent models. In the present study, we found that 3-O-acetyloleanolic acid, an active constituent isolated from the fruits of Forsythia suspensa, stimulated FGF21 production concomitant with the up-regulation of a transcription factor, nuclear receptor Nr4a1, in C2C12 myotubes. Additionally, significant increases in mFgf21 promoter activity were observed in C2C12 cells overexpressing TGR5 receptor in response to 3-O-acetyloleanolic acid treatment. Treatment with the p38 MAPK inhibitor SB203580 was effective at suppressing these stimulatory effects of 3-O-acetyloleanolic acid. Pretreatment with SB203580 also significantly repressed FGF21 mRNA abundance and FGF21 secretion in C2C12 myotubes after 3-O-acetyloleanolic acid stimulation, suggesting that p38 activation is required for the induction of FGF21 by ligand-activated TGR5 in C2C12 myotubes. These findings collectively indicated that TGR5 receptor signaling drives FGF21 expression via p38 activation, at least partly, by mediating Nr4a1 expression. Thus, the novel biological function of 3-O-acetyloleanolic acid as an agent having anti-obesity effects is likely to be mediated through the activation of TGR5 receptors.

Seasonality in physical activity and walking of healthy older adults.

BACKGROUND: An increasing number of older adults require improvements in their quality of life. Physical activities, particularly walking ability, are of primary importance for older adults. The influence of season on physical activity has not been sufficiently studied among older adults. Therefore, this report compared the physical activity and walking of older individuals between summer and winter seasons using a longitudinal study design in a community in a mid-latitude area. METHODS: Participants in the study comprised 39 healthy community-dwelling adults ranging in age from 65 to 80 years. Physical parameters and activities as well as the preferred speed of walking were measured at half-year intervals. RESULTS: Significant seasonal differences from summer to winter and from winter to summer were detected. Specifically, body fat percentage, single-leg stance, walking speed, cadence, stride length, and trunk and head-trunk pitch ranges were greater in winter than in summer, whereas grip strength and steps per day were greater in summer. Temperature and total activity level were considered to be related to body fat percentage. Grip strength was thought to be affected by outdoor temperature. The possibility of relationships between increased activity per unit time in older adults and increased preferred walking speed, cadence, and stride length in winter temperatures was discussed. CONCLUSION: The seasonal climatic environment of the geographic area of this study affected the activity level of the participants. These results indicate that seasonality should be considered when analyzing physical activity and walking in older adults.

Combined effects of age and gender on gait symmetry and regularity assessed by autocorrelation of trunk acceleration.

BACKGROUND: The gait of a healthy person is believed to be more regular and symmetrical than those of an individual with a disease. Thus, symmetry and regularity are important indicators of human gait. METHODS: The effects of age and gender on gait symmetry and regularity were investigated in 87 Japanese participants by measuring trunk accelerometry during a 7-m walk. The younger group included 26 female and 21 male students, and the elderly group included 24 females and 16 males. Average age for each group was 20 and 70 years, respectively. Gait symmetry and regularity were evaluated on the basis of autocorrelation functions of trunk accelerations of vertical and anteroposterior axes. RESULTS: The relationship between age and gait symmetry and regularity was statistically significant for both vertical and anteroposterior axes. Elderly participants showed lower symmetry and regularity in their gait than young participants. A significant gender effect was observed for the symmetry index of both axes but not for the regularity index. Male participants showed lower gait symmetry than females. An interaction effect between age and gender was significant in the symmetry index of anteroposterior acceleration. Gender effect was appeared more clearly in elderly than young participants. CONCLUSION: Elderly participants showed a more asymmetrical and irregular gait than young participants. In addition to age, a significant gender effect was observed on gait symmetry. However, the effect size of gender was smaller than that of age, and it was not significant for gait regularity. The gait indices obtained by autocorrelation of trunk acceleration can be considered useful to evaluate aging effect on gait.

Addition of an arch support improves the biomechanical effect of a laterally wedged insole.

In order to examine if the addition of an arch support could improve the biomechanical effect of the laterally wedged insole, three-dimensional gait analysis was performed on 20 healthy volunteers. Kinetic and kinematic parameters at the knee and subtalar joints were compared among the following four types of insoles; a 5-mm thick flat insole, a flat insole with an arch support (AS), a 6 degrees inclined laterally wedged insole (LW), and a laterally wedged insole with an arch support (LWAS). The knee adduction moment averaged for the entire stance phase was reduced by the use of LW and LWAS by 7.7% and 13.3%, respectively, from that with FLAT. The difference in knee adduction moment between LW and LWAS was most obvious in the late stance, which was ascribed to the difference in the progression angle between those insoles. The analyses also revealed that LW tended to increase step width, and that such an increase was completely eliminated by the addition of an arch support to LW. This reduction of step width could be another mechanism for the further reduction of the moment with LWAS. The analyses of biomechanical parameters at the subtalar joints suggested that LWAS allowed the subject to walk in a more natural manner, while exerting greater biomechanical effects than LW. Thus, the addition of an arch support to the laterally wedged insole reduced knee adduction moment more efficiently, possibly through the elimination of potential negative effects of the laterally wedged insole.

Inconsistent knee varus moment reduction caused by a lateral wedge in knee osteoarthritis.

OBJECTIVE: To determine--with the assistance of a larger sample size--whether the inconsistency of reducing the knee-joint varus moment with a lateral wedge in patients with medial compartment knee osteoarthritis (OA) persists and if so, what underlying mechanisms may explain it. DESIGN: Crossover design whereby 51 patients with bilateral isolated medial compartment knee OA and 19 age-matched healthy controls walked with two different wedge conditions: a 0-degree control wedge and a 6-degree lateral wedge. We conducted three-dimensional motion analysis, hip-knee-ankle (HKA) angle measurement, and radiologic assessment with Kellgren-Lawrence grade. We investigated frontal plane angles and moments at the knee and subtalar joints, ground reaction forces, and center of pressure (CoP). Moments were derived using a three-dimensional inverse dynamics model of the lower extremity. RESULTS: Nine patients (17.6%) had an increased knee-joint varus moment with the 6-degree lateral wedge via the medially shifted location of the CoP. These patients did not differ from the remaining patients in HKA angle and radiologic assessment. CONCLUSION: In approximately 18% of patients with bilateral medial compartment knee OA, the 6-degree lateral wedge seems to fail to reduce the knee-joint varus moment. The indication and limitations of lateral wedge should be confirmed by a randomized controlled study.

Effect of a lateral wedge on joint moments during gait in subjects with recurrent ankle sprain.

This study assessed the biomechanic effects of wearing a lateral wedge on the subtalar joint moment during gait in athletes with and without an unstable lateral ankle. A crossover design was applied whereby 50 collegiate males walked with two different wedges: a 0 degrees control wedge and a 6 degrees lateral wedge. We investigated frontal plane angles and moments at the subtalar joint and the knee joint, as well as ground reaction forces and center of pressure excursion. Moments were derived using a three-dimensional inverse dynamics model of the lower extremity. The 6 degrees lateral wedge significantly increased the subtalar joint valgus moment (P < 0.001) and reduced the knee joint varus moment (P < 0.001) when compared with no wedge. The differences between wedge conditions were associated with a laterally shifted location of the center of pressure during stance phase. However, there were diverse, sometimes reversed effects with the wedge among the athletes with an unstable lateral ankle. These results indicate that biomechanical indications and limitations of lateral wedges in unstable lateral ankles should be analyzed in more detail, possibly leading to new guidelines for the use of such foot orthoses.

Effects of laterally wedged insoles on knee and subtalar joint moments.

OBJECTIVE: To assess the biomechanic effects of wearing a lateral wedge on the knee joint varus moment during gait in elders with and without knee osteoarthritis (OA). DESIGN: Crossover design whereby subjects walked under 2 different insole conditions: a 0 degrees control wedge and a 6 degrees lateral wedge. SETTING: A gait laboratory with 3-dimensional motion analysis and force platform equipment. PARTICIPANTS: Thirteen healthy subjects and 13 knee patients with OA. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Frontal plane angles and moments at the knee and subtalar joints, ground reaction forces, and center of pressure. Moments were derived by using a 3-dimensional inverse dynamics model of the lower extremity. RESULTS: The 6 degrees lateral wedge significantly reduced knee joint varus moment and increased subtalar joint valgus moment in both groups when compared with no wedge. All patients had a greater knee joint varus moment with a similar subtalar joint valgus moment compared with the people without OA. There were diverse, sometimes reversed effects with the insole among the patients. CONCLUSIONS: The 6 degrees lateral wedge did not consistently reduce the knee joint varus moment in patients with knee OA. The biomechanic indications and limitations of laterally wedged insoles should be confirmed by a larger study.

Changes of joint moments in the gait of normal subjects wearing laterally wedged insoles.

OBJECTIVE: The purpose of this study was to assess the kinematic and kinetic effects of wearing a laterally wedged insole on the knee joint moment during gait, specifically in the frontal plane, in normal healthy adults. DESIGN: Motion analyses were conducted with (1) a three-dimensional motion analysis system and (2) ground reaction force analysis using force platforms when subjects walked under three different insole conditions: no wedge, a low wedge with a 3-degree lateral angle, and a high wedge with a 6-degree lateral angle. RESULTS: The high-wedge insole significantly reduced the knee joint varus moment during gait compared with the gait with the no-wedge insole. The actual segment angles at the subtalar and knee joints did not show any changes due to insole conditions. In contrast, the subtalar joint valgus moment increased for the high-wedge insole. This finding was correlated with a greater moment arm of the subtalar joint valgus moment with the high-wedge insole. CONCLUSIONS: These results indicate that, under dynamic conditions, the subjects wearing laterally wedged insoles had both changes of moments at the subtalar and knee joints via the more laterally shifted location of the center of pressure.

Induction of locomotor-like EMG activity in paraplegic persons by orthotic gait training.

This is, to our knowledge, the first report demonstrating the effects of orthotic gait training on the activity of the spinal locomotor neural networks. Three subjects with complete spinal cord injury (SCI) performed 1-h training with reciprocating gait orthosis 5 days/week for 12 weeks. The results showed that after 3 (n=1) or 6 weeks (n=2) of training, EMG activities synchronized with locomotor rhythm appeared in the soleus muscle (SOL) in all subjects, although very little EMG activity accompanied the orthotic gait at the early training stage. Our results suggest that the induced modulation in the SOL EMG waveforms might be attributable to changes in the orthotic gait movement pattern, and/or changes in the interneuronal activities of the spinal locomotor neural networks, as a result of orthotic gait training.