Metabolite Profiling Revealed That a Gardening Activity Program Improves Cognitive Ability Correlated with BDNF Levels and Serotonin Metabolism in the Elderly.

Metabolomics is useful for evaluating the fundamental mechanisms of improvements in the health functions of the elderly. Additionally, gardening intervention as a regular physical activity for the elderly maintained and improved physical, psychology, cognitive, and social health. This study was conducted to determine whether the cognitive ability of the elderly is affected by participating in a gardening activity program as a physical activity with a metabolomic potential biomarker. The gardening program was designed as a low to moderate intensity physical activity for the elderly. Serum metabolites resulting from gardening were subjected to metabolite profiling using gas chromatography time-of-flight mass spectrometry and ultra-high-performance liquid chromatography-linear trap quadruple-orbitrap-mass spectrometry followed by multivariate analyses. The partial least squares-discriminant analysis showed distinct clustering patterns among the control, non-gardening, and gardening groups. According to the pathway analysis, tryptophan metabolism including tryptophan, kynurenine, and serotonin showed significantly distinctive metabolites in the gardening group. Brain-derived neurotrophic factor levels (BDNF) in the gardening group were significantly increased after the gardening program. Correlation map analysis showed that the relative levels of tryptophan metabolites were positively correlated with BDNF. Our results show that tryptophan, kynurenine, and serotonin may be useful as metabolic biomarkers for improved cognitive ability by the gardening intervention.

Benefits of Gardening Activities for Cognitive Function According to Measurement of Brain Nerve Growth Factor Levels.

The objective of this study was to determine the effects of gardening activities in senior individuals on brain nerve growth factors related to cognitive function. Forty-one senior individuals (age 76.6 ± 6.0 years) were recruited from the local community in Gwangjin-gu, Seoul, South Korea. A 20-min low-to-moderate intensity gardening activity intervention, making a vegetable garden, was performed by the subjects in a garden plot located on the Konkuk University (Seoul, South Korea) campus. The gardening involved six activities including cleaning a garden plot, digging, fertilizing, raking, planting/transplanting, and watering. To determine the effects of the gardening activities on brain nerve growth factors related to memory, blood samples were drawn twice from each subject before and after the gardening activity by professional nurses. The levels of brain nerve growth factors, including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF), were analyzed. Levels of BDNF and PDGF were significantly increased after the gardening activity. This study revealed a potential benefit of gardening activities for cognitive function in senior individuals.

Platycodon grandiflorum-derived saponin enhances exercise function, skeletal muscle protein synthesis, and mitochondrial function.

Lower physical performance is an important risk factor in hypokinetic-related chronic disease, metabolic syndrome, and muscle atrophy. Our previous research demonstrated that Platycodon grandiflorum-derived saponin (PS) protects against eccentric exercise-induced muscle damage and mitochondrial function-related peroxisomal acyl-coenzme A oxidase (ACOX-1) and carnitine palmitoyltransferase (CPT-1) in high-fat diet-induced non-alcoholic steatohepatitis, and it inhibits osteoclast differentiation. However, the effects of PS on physical performance remain unknown. Therefore, we investigated whether PS enhances physical activity and skeletal muscle function. Supplementation with PS (2 mg/kg for 4 weeks) increased grip strength, wheel running repetition, and time to exhaustion in treadmill and swimming exercises. Marked increases in the synthesis of skeletal muscle proteins and muscle stem cell-related paired-box 7 (PAX7) were observed, and a decrease in the negative regulator myostatin was associated with enhanced muscle regeneration. Furthermore, PS induced expression of mitochondrial function proteins, including OXPHOS-III and -IV, in vivo and in vitro. These results suggest that PS enhances exercise function by ameliorating skeletal muscle protein synthesis and mitochondrial function.

The effects of either resveratrol or exercise on macrophage infiltration and switching from M1 to M2 in high fat diet mice.

PURPOSE: The aim of this study was to compare the effectiveness of either resveratrol supplementation or exercise training on macrophage infiltration and switching from M1 to M2 kupffer cells in high fat diet mice. METHODS: C57BL/6 mice were separated into 5 groups: normal diet (ND; n = 6), high-fat diet (HD; n = 6), high-fat diet with resveratrol (HR; n = 6), high-fat diet with exercise (HE; n = 6) or high-fat diet with resveratrol and exercise (HRE; n = 6). Resveratrol supplementation mice were orally gavaged with resveratrol (25mg/kg of body weight) dissolved in 50% propylene glycol. Exercise mice ran on a treadmill at 12-20 m/min for 30-60 min/day, 5 times/week for 12 weeks. RESULTS: After 12 weeks of intervention, the liver was analyzed. F4/80 expression was evaluated by western blot while CD11c and CD163 mRNA expressions were evaluated by RT-PCR. The weights of the body and liver were significantly increased in the HD and HR group compared to the ND group (p < 0.01). However, the weights were most effectively reduced in the HE and HRE groups compared to the HD group (p < 0.05). The macrophage marker, F4/80 expression was significantly lower in the HE and HRE groups compared to the HD group (p < 0.05). mRNA expression of the M1 macrophage marker, CD11c, in the HD group was significantly increased compared to the ND group (p < 0.01). mRNA expression of the M2 macrophage specific marker, CD163, in the HE and HRE groups were significantly increased compared to the HD group (p < 0.05). The mRNA expressions of TLR4, ICAM-1 and VCAM-1, which induce pro-inflammatory cytokine production, were strongly decreased in the HR, HE, and HRE groups compared to the HD group. CONCLUSION: These results suggest that moderate exercise training inhibits macrophage infiltration and up regulation of CD163 expression. However, resveratrol supplementation is not enough to ameliorate obesity-induced macrophage infiltration and switching.

Moderate exercise training is more effective than resveratrol supplementation for ameliorating lipid metabolic complication in skeletal muscle of high fat diet-induced obese mice.

PURPOSE: The aim of this study was to compare the effectiveness of moderate exercise training or resveratrol supplementation with a low fat diet on lipid metabolism in the skeletal muscle of high fat diet-induced obese mice. METHODS: C57BL/6J mice (5 weeks old, n = 30) were fed a high fat diet (45% fat) for 8 weeks first to make them obese. Afterward, all the mice were fed a low fat diet during 8 weeks of intervention with moderate exercise training and resveratrol supplementation. Before the intervention, the mice were separated into 3 groups: low-fat diet control (HLC; n = 10), low fat diet with resveratrol (HLR; n = 10) or low fat diet with exercise (HLE n = 10). The exercise group (HLE) performed treadmill running for 30-60 min/day at 10-22 m/min, 0% grade, 5 times/week for 8 weeks, while the resveratrol group (HLR) received a daily dose of resveratrol (10 mg/kg of body weight), 5 days/week for 8 weeks. RESULTS: Body weight was significantly reduced in HLE. Further, the lipogenesis marker SREBP and the inflammatory cytokine TNF-α were significant reduced in HLE. However, there was no significant effect from resveratrol supplementation with a low fat diet. Taken together, exercise training with a low fat diet has the positive effect of ameliorating lipid disturbance in the skeletal muscle of high fat diet-induced obese mice. CONCLUSION: These findings suggest that exercise training with a low fat diet is most effective to improve lipid metabolism by reducing lipogenesis and inflammation in the skeletal muscle of high fat diet-induced obese mice.

Exercise, but not quercetin, ameliorates inflammation, mitochondrial biogenesis, and lipid metabolism in skeletal muscle after strenuous exercise by high-fat diet mice.

PURPOSE: The purpose of this study was to investigate whether moderate exercise and quercetin intake with a low fat diet contribute to inflammatory cytokine production, mitochondrial biogenesis, and lipid metabolism in skeletal muscle after strenuous exercise by high-fat diet mice. METHODS: Male C57BL/6 mice were randomly divided into four groups: (1) High-fat for 12 weeks and low-fat diet control (C; n = 6); (2) high-fat diet for 12 weeks and low-fat diet with quercetin (Q; n = 4); (3) high-fat diet for 12 weeks and low-fat diet with exercise (E; n = 4); or (4) high-fat diet for 12 weeks and low-fat diet with exercise and quercetin (EQ; n = 5). Quercetin (10 mg/kg) was administered once per day, 5 day/week for 8 weeks. Exercise training was performed at moderate intensity for 8 weeks, 5 days/week for 30-60 min/day. Mice were subjected to a strenuous exercise bout of 60 min at a speed of 25 m/min (VO2 max 85%) conducted as an exercise-induced fatigue just before sacrifice. RESULTS: As results, body weights were significantly different among the groups. Exercise training significantly reduced inflammatory cytokines after strenuous exercise in skeletal muscle of high-fat diet mice. Exercise training increased Tfam mRNA in the soleus muscle after strenuous exercise. Exercise training significantly decreased lipogenesis markers in skeletal muscle of obese mice after strenuous exercise. Moderate exercise significantly increased lipolysis markers in the tibialis anterior muscle. CONCLUSION: These findings suggest that exercise training reduced inflammatory cytokine levels and improved mitochondrial biogenesis and lipid metabolism. However quercetin supplementation did not affect these parameters. Thus, long-term moderate exercise training has positive effects on obesity.

Exercise training is more effective than resveratrol supplementation on alleviation of inflammation in peritoneal macrophages of high fat diet mice.

PURPOSE: This study investigated the effect of exercise training and resveratrol supplementation with low fat diet on proinflammatory profiles by Lipopolysaccharide (LPS)-stimulation in peritoneal macrophage of high fat diet mice. METHODS: To accomplish the purpose of this study, C57BL/6 male mice were fed high fat diet (45% fat diet) for 8 weeks. Then these mice were divided into 3 groups; HLC (high fat diet and low fat diet for 8 weeks as the control, n=10), HLR (high fat diet and low fat diet for 8 weeks with resveratrol supplementation, n=10). HLE (high fat diet and low fat diet for 8 weeks with moderate exercise training, n=10). Resveratrol (10 mg/kg) was administrated once a day, 5 days/week for 8 weeks. Exercise training was performed for 8 weeks on a treadmill running for 30-60 min/day at 10-22 m/min, 0% grade, 5 days/week. After exercise training, all the peritoneal macrophage was collected and LPS (0, 0.5, 1.0 µg/ml) were used to stimulate the cells. Then peritoneal macrophage TNF-α, IL-6, MCP-1, IL12p70, IFN-γ, IL-10 were measured by BD cytometric bead array mouse inflammation kit. RESULTS: As a result, body weight and total cholesterol were significantly reduced in HLE compared with HLC (p<.05). Also, TNF-α and MCP-1 were decreased in HLE compared with HLC (p<.05) by LPS-stimulation (0, 0.5, 1.0 µg/ml) and IL-6, IL-12p70 and IFN-r were decreased in HLE compared with HLC (p<.05) by LPS-stimulation (1.0 µg/ml). But resveratrol supplementation did not affect the result. CONCLUSION: These findings suggest that exercise training has beneficial effects on body weight, total cholesterol, peritoneal macrophage and proinflammatory cytokine in high fat diet mice.

Moderate intensity exercise inhibits macrophage infiltration and attenuates adipocyte inflammation in ovariectomized rats.

PURPOSE: The purpose of this study was to investigate the effects of the different endurance exercise intensities on the macrophage infiltration and adipocyte inflammation of ovariectomized rats. METHODS: 24 female SD rats (6 weeks old) were randomly assigned to sham control (SC; n=6), ovariectomized control (OC; n=6), ovariectomized low intensity exercise (OL; n=6), and ovariectomized moderate intensity exercise (OM; n=6) groups. The two training groups ran for 60 min/day, 5 times/ week at 18 and 26m/min for 16 weeks. Twenty-four hours after the last exercise session, rats were sacrified, and epididymal pads were analyzed. F4/80 and IL-6 expressions were evaluated by western blotting. ICAM-1, VCAM-1 TLR4, TNF-α, and MCP-1 mRNA expressions were evaluated by RT-PCR. RESULTS: In comparison with OC group, OM group showed significantly lower body weight gain and adipose tissue mass. Also, OM group markedly inhibited F4/80 expression, adhesion molecule (ICAM-1, VCAM-1) and pro-inflammatory cytokines (TLR4, TNF-α, MCP-1) mRNA expressions in adipose tissue. In contrast, OL group partially prevented body weight gain while other examined parameter were unaffected by low intensity exercise training. CONCLUSION: The results of this study suggest that OM group inhibits visceral macrophage infiltration by suppressing the adhesion molecules. It may also attenuate cytokine production in the adipose tissue by repressing the TLR4-mediated pro-inflammatory signaling cascades in ovariectomized rats.