Weight-loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD.

BACKGROUND & AIMS: A weight-loss-independent beneficial effect of exercise on non-alcoholic fatty liver disease (NAFLD) management has been reported, but the underlying mechanism is unknown. To help determine this mechanism, the effects of exercise on individual tissues (liver, adipose tissue, and skeletal muscle) were retrospectively studied. METHODS: Data from Japanese obese men with NAFLD in a 3-month exercise regimen were analysed and compared with those in a 3-month dietary restriction program designed to achieve weight loss. The underlying mechanism was studied in a smaller subcohort. RESULTS: Independent of the effect of weight loss, the exercise regimen reduced liver steatosis by 9.5% and liver stiffness by 6.8% per 1% weight loss, and resulted in a 16.4% reduction in FibroScan-AST score. Improvements in these hepatic parameters were closely associated with anthropometric changes (reduction in adipose tissue and preservation of muscle mass), increases in muscle strength (+11.6%), reductions in inflammation and oxidative stress (ferritin: -22.3% and thiobarbituric acid: -12.3%), and changes in organokine concentrations (selenoprotein-P: -11.2%, follistatin: +17.1%, adiponectin: +8.9%, and myostatin: -21.6%) during the exercise regimen. Moreover, the expression of target genes of the transcription factor Nrf2, an oxidative stress sensor, was higher in monocytes, suggesting that Nrf2 is activated. Large amounts of high-intensity exercise were effective at further reducing liver steatosis and potentiating improvements in pathophysiological parameters (liver enzyme activities and organokine profiles). CONCLUSIONS: The weight-loss-independent benefits of exercise include anti-steatotic and anti-stiffness effects in the livers of patients with NAFLD. These benefits seem to be acquired through the modification of inter-organ crosstalk, which is characterised by improvements in organokine imbalance and reductions in inflammation and oxidative stress. LAY SUMMARY: We investigated the effects of exercise on non-alcoholic fatty liver disease (NAFLD) that were not related to weight loss. We found that exercise had considerable weight-loss-independent benefits for the liver through a number of mechanisms. This suggests that exercise is important for NAFLD patients, regardless of whether they lose weight.

Association of Foot Structure with the Strength of Muscles that Move the Ankle and Physical Performance.

The human foot plays an important role in supporting body weight, maintaining postural balance, and absorbing ground reaction forces. Although many studies have indicated that a causal relationship exists between foot structure and alterations in lower extremity kinematics, there is little evidence regarding the possible association of foot structure with strength of muscles that move the ankle and physical performance. A total of 67 adult men with a mean age of 51.19 ± 8.82 years participated in this study. Foot structural parameters were assessed using a 3-dimensional foot scanner. Strength of muscles that move the ankle was measured with a dynamometer. Physical performance items, including agility, force, and proprioception, were also measured. We found that all the measured parameters of the length, width, girth, and height of the foot were positively correlated with the strength of plantarflexion, dorsiflexion, eversion, and inversion (r ranged from 0.26 to 0.57; p < .05). Moreover, all or part of the parameters of the length, width, and girth of the foot but not the height and angles of the foot were correlated significantly with vertical jump, stepping forward and backward, and stepping side to side (r ranged from 0.25 to 0.44; p < .05). These findings indicate a weak-to-moderate association between foot structure and the strength of muscles that move the ankle, as well as physical performance. We therefore suggest that a larger foot may have greater muscle strength of the ankle joint and better physical performance.

Mild-to-Moderate Hallux Valgus Does Not Decrease Ankle Muscle Strength in Middle-Aged Japanese Women: A Comparative Study.

Extreme hallux valgus has been documented to be related to lower functional ability and health-related quality of life. It also has a negative effect on foot structure and biomechanical characteristics, which in turn may affect muscle strength in the foot and ankle. Thus, the purposes of this study were to determine whether there is a difference of ankle muscle strength in varied hallux valgus deformities and to investigate correlations between hallux valgus angles and ankle muscle strength. Hallux valgus angles and ankle muscle strength data were collected from 31 middle-aged Japanese women. The hallux valgus angle was measured with a 3-dimensional foot scanner; ankle muscle strength was measured with a dynamometer. Results showed no differences in ankle muscle strength between normal and mild-to-moderate hallux valgus at both 60º/second and 120º/second (p > .05). Unexpectedly, women with mild-to-moderate hallux valgus had a greater value for inversion peak torque per body weight and eversion-to-inversion ratio than those with normal hallux valgus (p = .019 and p = .022) at 120º/second. Furthermore, hallux valgus was correlated with inversion peak torque and peak torque per body weight (r = 0.47; p = .012 and r = 0.50; p = .007) and associated with eversion-to-inversion strength ratio (r = -0.47; p = .012). The findings indicated that mild-to-moderate hallux valgus did not result in a decrease in ankle muscle strength. Conversely, mild-to-moderate hallux valgus had greater ankle inversion strength in middle-aged Japanese women. Further studies are needed to investigate ankle muscle strength in severe hallux valgus deformities.

Increasing Physical Activity Might Be More Effective to Improve Foot Structure and Function Than Weight Reduction in Obese Adults.

Obesity is reported to be an important factor affecting foot structure and function. For obese individuals, weight reduction or increasing weight physical activity could be an effective approach to improve foot structure and function. The present study sought to determine the effect of weight reduction and increasing physical activity on foot structure and function in obese Japanese and to investigate which intervention is more beneficial. The participants were divided into the weight reduction group (n = 30; body mass index 29.0 ± 2.5 kg/m2), with the intervention consisting of dietary modification, and the increasing physical activity group (n = 15; body mass index 28.2 ± 3.1 kg/m2), with the intervention consisting of walking and jogging. A 3-dimensional foot scanner was used to measure the foot anthropometric data with the participants both sitting and standing. The dorsum height declined and the arch stiffness index increased after the weight reduction intervention, and the truncated foot length decreased and the arch stiffness index increased after the increasing physical activity intervention (p <.05). The arch height index showed a downward trend after the weight reduction intervention (p = .060) and an upward trend after the increasing physical activity intervention (p = .069). Moreover, a greater change was found in the increase of the dorsum height and arch height index and decrease of the truncated foot length in the increasing physical activity group than in the weight reduction group (p <.05). These findings suggest that increasing physical activity might be more effective to improve foot structure and function than weight reduction in obese adults.

Does Weight Reduction Affect Foot Structure and the Strength of the Muscles That Move the Ankle in Obese Japanese Adults?

Obesity is considered a major influential factor of foot structure and function. It has been reported to result in detrimental alterations of foot structure indicators and a decrease in muscle strength, which can lower the quality of life and increase the morbidity of obesity. The purpose of the present study was to determine the effect of weight reduction on foot structure and the strength of the muscles that move the ankle in obese adults. A total of 33 obese Japanese participants (mean body mass index 28.49 ± 2.87 kg/m2) without an exercise habit participated in a 12-week dietary modification program. Their foot structure indicators were measured using a 3-dimensional foot scanner, and the strength of the muscles that move the ankle was assessed using a dynamometer. After the dietary modification, the mean body weight reduction was 7.49 ± 4.10 kg (9.38%; 77.82 ± 13.26 kg before and 70.33 ± 11.37 kg after; p <.001). The wide foot indicators, including the forefoot girth, rearfoot width, and instep girth, had decreased significantly (p <.05), and the decreases correlated positively with the weight reduction. Regarding the strength of the muscles that move the ankle, except for dorsiflexion, all the measured peak torque values per body weight had increased significantly (p <.01). These results suggest that the weight reduction induced by a 12-week dietary modification results in thinner feet and increased strength of the muscles that move the ankle.

Which cytokine is the most related to weight loss-induced decrease in arterial stiffness in overweight and obese men?

Obesity and increased arterial stiffness are risk factors for cardiovascular disease. A well-known characteristic of obesity is the chronic low-grade inflammatory state, and it causes elevation of arterial stiffness. Weight-loss reduces arterial stiffness and inflammatory level in obese individuals. However, it is unclear which inflammatory factor is most related to weight loss-induce decreases in arterial stiffness in overweight and obese men. Thus, the aim of this study was to determine which circulating cytokine level has the most effect on decreasing arterial stiffness after lifestyle modification. Twenty overweight and obese men completed a 12-week period of lifestyle modifications (combination of aerobic exercise training and dietary modification). We measured brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness, and circulating cytokine levels using comprehensive analysis. After the 12-week lifestyle modifications, body mass was markedly decreased. Also, baPWV and the levels of several circulating cytokines significantly decreased after the lifestyle modifications. We observed a positive correlation between changes in baPWV and circulating interleukin-6 (IL-6) levels. Furthermore, multiple liner regression analysis revealed that change in baPWV was significantly associated with that in IL-6 levels after consideration of changes in systolic blood pressure and body mass index. These results suggest that for overweight and obese men, a 12-week period of lifestyle modifications-induced a decrease in circulating cytokine levels (especially IL-6 levels), leads to decreased baPWV.

Increased physical activity has a greater effect than reduced energy intake on lifestyle modification-induced increases in testosterone.

Obesity has reached epidemic proportions worldwide. Obesity results in reduced serum testosterone levels, which causes many disorders in men. Lifestyle modifications (increased physical activity and calorie restriction) can increase serum testosterone levels. However, it is unknown whether increased physical activity or calorie restriction during lifestyle modifications has a greater effects on serum testosterone levels. Forty-one overweight and obese men completed a 12-week lifestyle modification program (aerobic exercise training and calorie restriction). We measured serum testosterone levels, the number of steps, and the total energy intake. We divided participants into two groups based on the median change in the number of steps (high or low physical activities) or that in calorie restriction (high or low calorie restrictions). After the program, serum testosterone levels were significantly increased. Serum testosterone levels in the high physical activity group were significantly higher than those in the low activity group. This effect was not observed between the groups based on calorie restriction levels. We found a significant positive correlation between the changes in serum testosterone levels and the number of steps. Our results suggested that an increase in physical activity greatly affected the increased serum testosterone levels in overweight and obese men during lifestyle modification.

Lifestyle modification increases serum testosterone level and decrease central blood pressure in overweight and obese men.

Obesity has reached global epidemic proportions and is associated with multiple comorbidities, including cardiovascular disease. A novel predictor of cardiovascular disease is elevated central systolic blood pressure. In fact, lifestyle modifications have been shown to decrease the central systolic blood pressure in overweight and obese men. The mechanism underlying these changes has yet to be fully elucidated. Interestingly, testosterone has been found to have cardioprotective effects. Moreover, serum testosterone levels are lower in obese men than in normal weight men. However, it is still unclear whether testosterone participates in the decrease of central blood pressure in overweight and obese men following lifestyle modifications. So, the purpose of the present study was to investigate the effect of testosterone on central systolic blood pressure in overweight and obese men before and after the 12-week lifestyle modification program. Forty-four overweight and obese men completed a 12-week lifestyle modification program (aerobic exercise training and dietary modifications). For all participants, central systolic blood pressure and serum testosterone levels were measured before and after the program. After the program, central systolic blood pressure was significantly decreased while serum total testosterone levels were significantly increased in overweight and obese men. Moreover, we also found a significant negative relationship between the change in serum testosterone levels and that in central systolic blood pressure. The present study suggests that increased serum testosterone levels likely contribute to a decrease in central blood pressure in overweight and obese men.

Lifestyle modification decreases arterial stiffness in overweight and obese men: dietary modification vs. exercise training.

Obesity and increased arterial stiffness are independent risk factors for cardiovascular disease. Arterial stiffness is increased in obese individuals than in age-matched nonobese individuals. We demonstrated that dietary modification and exercise training are effective in reducing arterial stiffness in obese persons. However, the differences in the effect on arterial stiffness between dietary modification and exercise training are unknown. The purpose of the current study was to compare the effect of dietary modification and aerobic exercise training on arterial stiffness and endothelial function in overweight and obese persons. Forty-five overweight and obese men (48 ± 1 year) completed either a dietary modification (well-balanced nutrient, 1680 kcal/day) or an exercise-training program (walking, 40-60 min/day, 3 days/week) for 12 weeks. Before and after the intervention, all participants underwent anthropometric measurements. Arterial stiffness was measured based on carotid arterial compliance, brachial-ankle pulse wave velocity (baPWV), and endothelial function was determined by circulating level of endothelin-1 (ET-1) and nitric oxide metabolite (nitrites/nitrate as metabolite: NOx). Body mass and waist circumference significantly decreased after both intervention programs. Weight loss was greater after dietary modification than after exercise training (-10.1 ± 0.6 kg vs. -3.6 ± 0.5 kg, p < .01). Although arterial stiffness and the plasma levels of ET-1 and NOx were improved after dietary modification or exercise training, there were no differences in those improvements between the 2 types of interventions. Exercise training improves arterial function in obese men without as much weight loss as after dietary modification.

Abdominal obesity: causal factor or simply a symptom of obesity-related health risk.

BACKGROUND: Abdominal fat (AF) reduction is advocated in the treatment of obesity-related diseases. Nonetheless, recent studies have shown additional beneficial effects against obesity-related health risks, independent of AF reduction. Therefore it is important to determine whether AF plays a causal role in promoting metabolic disorders or is simply a symptom of increased obesity-related health risk factors. Clarification of the primary role of AF in the pathogenesis of obesity-related disease is also important. OBJECTIVE: This retrospective study was conducted with the objectives of 1) comparison between groups exhibiting equivalent amounts of AF loss that resulted from distinct treatments (exercise and dietary restriction) with respect to degrees of improvement in obesity-related health risk factors and 2) determination of definite differences in the outcomes of obesity-related health risk in subjects receiving identical treatment (exercise) but exhibiting a remarkable difference in AF reduction. DESIGN: In 66 subjects who completed a 12-week exercise or dietary restriction program, 17 parameters (systolic blood pressure [SBP] and diastolic blood pressure [DBP]; high-sensitivity C-reactive protein [hs-CRP]; leptin, adiponectin, tumor necrosis factor [TNF]-α, interleukin [IL]-6; alanine aminotransferase [ALT], gamma glutamyl transpeptidase [γGT]; lipid profile: high-density lipoprotein cholesterol [HDLC], triglyceride [TG]; fasting plasma glucose [FPG], hemoglobin A1c [HbA1c], homeostasis model assessment of insulin resistance (HOMA-IR); creatinine, uric acid; and maximal aerobic capacity [VO2 max]) were examined as indicators of obesity-related health risk. RESULTS: Despite equivalent magnitudes of AF reduction (-29.5% versus -30.1%) in subjects in the exercise and dietary restriction groups (objective 1), ten parameters (SBP, DBP, HDLC, HOMA-IR, uric acid, creatinine, hs-CRP, adiponectin, IL-6, and VO2 max) showed significant differences. However, for large AF reduction differences (-30.1% versus -2.8%) between groups of subjects in the same exercise program (objective 2), only creatinine and VO2 max were different. CONCLUSION: It is likely that AF reduction alone is not directly linked to improvement in obesity-related health risk factors, indicating the need for reexamination of the management for AF reduction (ie, lifestyle modification) rather than simply targeting reduction of AF.

Effects of exercise training on circulating retinol-binding protein 4 and cardiovascular disease risk factors in obese men.

INTRODUCTION: The purpose of this study was to investigate the effects of 12-week exercise training on circulating retinol-binding protein 4 (RBP4) concentration and cardiovascular disease (CVD) risk factors in obese men. METHODS: 29 obese men (age 48 ± 2 years; BMI 29.6 ± 0.7 kg/m(2)) participated in a 12-week exercise program (50-70% maximal heart rates; 3 times/week) without calorie restriction. Anthropometric parameters, CVD risk factors (total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol, triglycerides (TG), and quantitative insulin sensitivity check index), and circulating RBP4 and adipokine (adiponectin, leptin, and interleukin-6 (IL-6)) concentrations were measured. RESULTS: Exercise training significantly improved in absolute peak oxygen consumption (p < 0.05), and CVD risk factors (p < 0.05), with the exception of HDLC. There was a significant decrease in circulating RBP4, leptin, and IL-6 concentrations (p < 0.05). Stepwise regression analysis revealed that changes in RBP4 concentration were independently related to the changes in TG concentration (ß = 0.46, p < 0.05). CONCLUSION: These results demonstrate that exercise training without calorie restriction improves several CVD risk factors and circulating RBP4 and adipokine concentrations. Moreover, the change in circulating RBP4 may be more associated with the improvements in TG concentration in obese men.

Efficiency of a free-living physical activity promotion program following diet modification for fat loss in Japanese obese men.

The aim of the current study was to examine the efficiency of a free-living physical activity promotion (PAP) program following a diet modification program for fat loss. Fifty obese men, aged 51.4±7.0 y, received a 6-mo regimen consisting of 2 phases. Weekly 90-min free-living PAP sessions were provided for 3 mo immediately after a 3-mo diet modification phase. Fat mass (FM) was measured at baseline and at months 3 and 6 using dual energy X-ray absorptiometry. The time spent in moderate-vigorous physical activity (MVPA) was monitored by a validated single-axis accelerometer. The total energy intake of all participants was assessed at baseline and during weeks 9 and 10 of both the diet modification and PAP programs. The change (Δ) in FM was -1.4±1.9 kg (p<0.05) during the PAP program after the diet modification program (-4.3±2.9 kg, p<0.01). Although there was no significant relationship between ΔFM and ΔMVPA during the PAP phase (p=0.11), MVPA was significantly increased during the PAP phase (+76.0±146.5 min/wk, p<0.01). However, a significant correlation was observed between energy intake/weight and MVPA during the PAP program (r=0.39). Our results suggest that the magnitude of expected FM loss induced by an increase in PA may be suppressed as a result of increased energy intake, even during a PAP program after a diet modification program.