Factors of Obesity and Metabolically Healthy Obesity in Asia.

The East Asian region (China, Japan, and South Korea) is comprised of almost 1.5 billion people and recent industrialization has brought with it a pandemic of rising obesity, even in children. As these countries are rapidly aging and functioning at sub-replacement birthrates, the burgeoning costs of obesity-related care may threaten socialized healthcare systems and quality of life. However, a condition called metabolically healthy obesity (MHO) has been found to be without immediate cardiopulmonary or diabetic risk. Thus, maintenance of the MHO condition for the obese in East Asia could buffer the burden of long-term obesity care on medical systems and knowledge of the biochemical, genetic, and physiological milieu associated with it could also provide new targets for intervention. Diverse physiological, psychological, environmental, and social factors play a role in obesogenesis and the transition of MHO to a metabolically unhealthy obesity. This review will give a broad survey of the various causes of obesity and MHO, with special emphasis on the East Asian population and studies from that region.

A favorable metabolic profile in metabolically healthy obesity is associated with physical activity level rather than abdominal fat volume in Japanese males.

[Purpose] To determine the potential factors for difference in metabolic profiles between metabolically healthy obesity and metabolically unhealthy obesity, we investigated the difference in abdominal fat volume, metabolic characteristics, and physical activity levels between metabolically healthy obesity and metabolically unhealthy obesity identified with cardiovascular disease risk factors in Japanese males. [Participants and Methods] Of 305 volunteers recruited, 130 obese males (age: 46.9 ± 8.9 years; body mass index: 29.6 ± 3.5 kg/m2) met the criteria for the study. They were divided into two groups; metabolically healthy obesity and metabolically unhealthy obesity according to cardiovascular disease risk factors including low-density lipoprotein cholesterol. Abdominal fat volumes were measured using magnetic resonance imaging. Cardiovascular disease risk factors and metabolic characteristics were evaluated by blood pressure and blood parameters. Physical activity levels were measured using an accelerometer. [Results] Despite the fact that metabolically healthy obesity had a more favorable metabolic profile than the metabolically unhealthy obesity, no significant differences in visceral and subcutaneous fat volumes were found between the two groups. Moreover, the metabolically healthy obesity had a significantly greater physical activity expenditure and moderate-to-vigorous physical activity level than the metabolically unhealthy obesity. [Conclusion] A more favorable metabolic profile in metabolically healthy obesity may be associated with physical activity level rather than abdominal fat volumes in Japanese males.

Sedentary behaviour, physical activity, and renal function in older adults: isotemporal substitution modelling.

BACKGROUND: Physical inactivity and sedentary behaviour (too much sitting) can contribute to renal dysfunction. However, the potential benefits of behavioural change (e.g. replacing sedentary behaviour with physical activity) on renal function are not well understood. We used isotemporal substitution to model potential impacts of behaviours on renal function by replacing time spent in one behaviour to another. METHODS: In 174 older Japanese adults (age, 50-83 years; females, 76%), the time spent in sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were assessed using an uniaxial accelerometer. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) from serum creatinine and cystatin C levels. RESULTS: In univariate analyses, eGFR was significantly, albeit weakly, correlated with time spent in sedentary behaviour (rs = - 0.229), LPA (rs = 0.265), and MVPA (rs = 0.353). In the isotemporal substitution models, replacement of 30 min/day of sedentary behaviour with an equivalent LPA time was not significantly associated with eGFR (ß = 2.26, p = 0.112); however, replacement with an equivalent time of MVPA was beneficially associated with eGFR (ß = 5.49, p < 0.05). CONCLUSIONS: These cross-sectional findings suggest that sedentary behaviour (detrimentally) and physical activity (beneficially) may affect renal function and that replacing sedentary behaviour with MVPA may benefit renal health in older adults.

Association between duration of excessive weight and arterial stiffness in middle-aged and older adults.

This study aims to evaluate the association between duration of overweight/obesity and arterial stiffness. In total, 103 men and women aged 45-68 years with a body mass index (BMI) of ≥25 kg/m2 were enrolled in this study. Duration of overweight/obesity was calculated for individuals with at least two consecutive BMI occurrences of ≥25 kg/m2 in the previous (5-year intervals from 20 years old) and present BMI information. Multiple regression analysis showed that carotid-femoral pulse wave velocity, an index of arterial stiffness, was independently associated with the duration of overweight/obesity, but not with current degree of overweight/obesity.

Physical Fitness Levels among Colon Cancer Survivors with a Stoma: A Preliminary Study.

Background and Objectives: Stoma surgery is linked to reduced physical activity in colon cancer survivors and leads to decreased physical fitness, activity of daily living dysfunction, and poorer quality of life. However, few studies have investigated the physical fitness levels of colon cancer survivors living with stomas. This study aimed to compare the physical fitness levels of colon cancer survivors with stomas and healthy adults, assessing them in a variety of dimensions (e.g., strength and flexibility) and in terms of physical fitness age (PFA), an integrated index of overall fitness. Materials and Methods: The study population consisted of 17 colon cancer survivors with (stoma group) and 20 healthy adults without (control group) a stoma. Physical fitness was assessed using a battery of five tests: repeated back-and-forth steps, 30-s chair stand, chair sit-and-reach, grip strength, and single-leg balance with eyes closed. Respective performance values were converted into PFA, which was compared between the stoma and control groups. Fitness indicators were compared between groups by analysis of covariance, and PFA and chronological age (CA) by paired t-tests. Results: The mean ages (±standard deviation) of the stoma and control groups were 74.1 ± 7.9 and 73.5 ± 7.1 years, respectively. Colon cancer survivors with stomas had poorer lower limb muscular strength, endurance, and flexibility than controls. In the stoma group, the marginal mean (±standard error) PFA was calculated to be 82.5 ± 3.7 years, significantly higher than the CA and PFA of the control group (69.6 ± 3.9 years). Conclusions: Colon cancer survivors with stomas have lower physical fitness levels than healthy adults, with apparent deficits in lower limb flexibility, muscular strength, and endurance. Our findings demonstrated the need for exercise interventions in this population, focusing on these dimensions of fitness. However, our results should be corroborated by means of a larger-scale comparison in future studies.

Aerobic exercise training normalizes central blood pressure regulation after oral glucose loading in overweight/obese men.

Central systolic blood pressure (cSBP) decreases after a meal or glucose challenge, but this response is impaired in obesity-related disorders. We investigated whether aerobic exercise training improves cSBP regulation during an oral glucose tolerance test (OGTT) in overweight/obese men. Thirteen overweight/obese men and six normal-weight men (as an alternative comparison instead of a no-exercise group) completed a 12-week aerobic exercise training program. Before and after the program, cSBP (i.e., radial second systolic pressure) was measured using an applanation tonometry at fasting and both 60 min and 120 min after 75 g glucose loading. Before and during the program, physical activity (PA) time was recorded using a tri-axial accelerometer. Pre-training, cSBP was significantly decreased with glucose loading in normal-weight men, while cSBP did not change in overweight/obese men. Post-training, a significant decrease in cSBP was observed in both groups following glucose loading. In addition, the increase in vigorous PA time during the exercise program was significantly correlated to the increase in area above the curve for cSBP during OGTT (demonstrating an improvement in the cSBP response to glucose loading) after the exercise program. These findings may provide novel insights into the role of PA in reducing the cardiovascular risk in obesity.

Vigorous Physical Activity is Associated with Regular Aerobic Exercise-Induced Increased Serum Testosterone Levels in Overweight/Obese Men.

Testosterone is a male sex hormone and low circulating testosterone levels are associated with various health disorders in men. Obesity results in reduced circulating testosterone levels in men. Previously, we demonstrated that lifestyle modifications (combination of aerobic exercise and dietary modification) increase circulating testosterone levels in overweight/obese men. However, the effect of regular aerobic exercise on serum testosterone levels remains unclear. The purpose of this study was to investigate the effect of a 12-week aerobic exercise intervention on circulating testosterone levels in normal-weight and overweight/obese men. Sixteen normal-weight men and twenty-eight overweight/obese men completed a 12-week aerobic exercise intervention. Before and after the intervention, we measured serum total testosterone, free testosterone, and bioavailable testosterone levels, and categorized the physical activity levels (light, moderate, or vigorous) in all participants. At baseline, serum total testosterone, free testosterone, and bioavailable testosterone levels were significantly lower in overweight/obese men than in normal-weight men (all p<0.01). After the 12-week aerobic exercise intervention, serum total testosterone, free testosterone, and bioavailable testosterone levels significantly increased in overweight/obese men (p<0.01). In addition, stepwise multivariable linear regression analysis revealed the increase in vigorous physical activity was independently associated with increased serum total testosterone levels (ß=0.47, p=0.011). We demonstrated that a 12-week aerobic exercise intervention increased serum total testosterone, free testosterone, and bioavailable testosterone levels in overweight/obese men. We suggest that an increase in vigorous physical activity increased circulating testosterone levels in overweight/obese men.

MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome segregation.

Xeroderma pigmentosum group D (XPD) protein is one of the subunits of TFIIH that is required for nucleotide excision repair and transcription. We found a XPD protein complex containing MMS19 that was assumed to be a regulator of TFIIH. However, the MMS19-XPD complex did not contain any other subunits of TFIIH. Instead, it included FAM96B (now designated MIP18), Ciao1, and ANT2. MMS19, MIP18, and XPD localized to the mitotic spindle during mitosis. The siRNA-mediated knockdown of MMS19, MIP18, or XPD led to improper chromosome segregation and the accumulation of nuclei with abnormal shapes. In addition, the frequency of abnormal mitosis and nuclei was increased in XP-D and XP-D/CS patients' cells. These results indicate that the MMS19-XPD protein complex, now designated MMXD (MMS19-MIP18-XPD), is required for proper chromosome segregation, an abnormality of which could contribute to the pathogenesis in some cases of XP-D and XP-D/CS.

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.

Urinary liver-type fatty acid-binding protein is associated with subendocardial viability ratio in middle- and older-aged adults.

BACKGROUND: To identify one of the physiological underlying mechanisms of the predictive effects of urinary liver-type fatty acid-binding protein (L-FABP) for the onset of cardiovascular disease (CVD), we investigated the relationship between urinary L-FABP levels and subendocardial viability ratio (SEVR), a marker of myocardial perfusion, in middle- and older-aged adults. METHODS: This was a cross-sectional study of 249 middle- and older-aged adults (aged 46-83 years). We measured urinary L-FABP levels and central hemodynamic parameters, including SEVR, calculated by pulse wave analysis using an applanation tonometry. RESULTS: In the participants stratified in accordance with the tertiles of urinary L-FABP levels, SEVR decreased in a stepwise fashion with increasing tertiles (p < 0.001). Furthermore, this association remains significant after the consideration of various confounders. On the contrary, urinary albumin levels were not independently related with SEVR. CONCLUSION: Our results demonstrated that urinary L-FABP levels were independently associated with the SEVR of the middle- and older-aged adults. This result suggests that the increase in urinary L-FABP levels even within the normal range might be related to the decrease in myocardial perfusion (SEVR).

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.

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.

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.

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.

Relationships between serum free fatty acid and pulse pressure amplification in overweight/obese men: insights from exercise training and dietary modification.

Pulse pressure amplification (i.e., the ratio of peripheral to central pulse pressure) is a strong predictor of cardiovascular events. Circulating free fatty acid, which is a major cause of insulin resistance, has been reported to favorably be associated with pulse pressure amplification in the arm (from the aorta to brachial artery). We hypothesized that this paradoxical relationship depended on an evaluating site of pulse pressure amplification and investigated whether serum free fatty acid level is related to pulse pressure amplification in the arm or trunk (from the aorta to femoral artery) in overweight/obese men. In a cross-sectional study, 85 men participated, and regression analyses revealed that serum free fatty acid level was significantly and independently associated with pulse pressure amplification in the arm but not the trunk. In a longitudinal study, 33 men completed a 12-week lifestyle intervention that involved both exercise training and dietary modification. The lifestyle intervention-induced change in serum free fatty acid level was significantly correlated to that in pulse pressure amplification in the arm but not the trunk. These results support our hypothesis and suggest that pulse pressure amplification should be measured in the trunk instead of the arm in overweight/obese men to simplify its interpretation.

The C-terminal Region and SUMOylation of Cockayne Syndrome Group B Protein Play Critical Roles in Transcription-coupled Nucleotide Excision Repair.

Cockayne syndrome (CS) is a recessive disorder that results in deficiencies in transcription-coupled nucleotide excision repair (TC-NER), a subpathway of nucleotide excision repair, and cells from CS patients exhibit hypersensitivity to UV light. CS group B protein (CSB), which is the gene product of one of the genes responsible for CS, belongs to the SWI2/SNF2 DNA-dependent ATPase family and has an ATPase domain and an ubiquitin-binding domain (UBD) in the central region and the C-terminal region, respectively. The C-terminal region containing the UBD is essential for the functions of CSB. In this study, we generated several CSB deletion mutants and analyzed the functions of the C-terminal region of CSB in TC-NER. Not only the UBD but also the C-terminal 30-amino acid residues were required for UV light resistance and TC-NER. This region was needed for the interaction of CSB with RNA polymerase II, the translocation of CS group A protein to the nuclear matrix, and the association of CSB with chromatin after UV irradiation. CSB was modified by small ubiquitin-like modifier 2/3 in a UV light-dependent manner. This modification was abolished in a CSB mutant lacking the C-terminal 30 amino acid residues. However, the substitution of lysine residues in this region with arginine did not affect SUMOylation or TC-NER. By contrast, substitution of a lysine residue in the N-terminal region with arginine decreased SUMOylation and resulted in cells with defects in TC-NER. These results indicate that both the most C-terminal region and SUMOylation are important for the functions of CSB in TC-NER.

Stabilization of Ultraviolet (UV)-stimulated Scaffold Protein A by Interaction with Ubiquitin-specific Peptidase 7 Is Essential for Transcription-coupled Nucleotide Excision Repair.

UV-sensitive syndrome is an autosomal recessive disorder characterized by hypersensitivity to UV light and deficiency in transcription-coupled nucleotide excision repair (TC-NER), a subpathway of nucleotide excision repair that rapidly removes transcription-blocking DNA damage. UV-sensitive syndrome consists of three genetic complementation groups caused by mutations in the CSA, CSB, and UVSSA genes. UV-stimulated scaffold protein A (UVSSA), the product of UVSSA, which is required for stabilization of Cockayne syndrome group B (CSB) protein and reappearance of the hypophosphorylated form of RNA polymerase II after UV irradiation, forms a complex with ubiquitin-specific peptidase 7 (USP7). In this study, we demonstrated that the deubiquitination activity of USP7 is suppressed by its interaction with UVSSA. The interaction required the tumor necrosis factor receptor-associated factor domain of USP7 and the central region of UVSSA and was disrupted by an amino acid substitution in the tumor necrosis factor receptor-associated factor-binding motif of UVSSA. Cells expressing mutant UVSSA were highly sensitive to UV irradiation and defective in recovery of RNA synthesis after UV irradiation. These results indicate that the interaction between UVSSA and USP7 is important for TC-NER. Furthermore, the mutant UVSSA was rapidly degraded by the proteasome, and CSB was also degraded after UV irradiation as observed in UVSSA-deficient cells. Thus, stabilization of UVSSA by interaction with USP7 is essential for TC-NER.

Does attending an exercise class with a spouse improve long-term exercise adherence among people aged 65 years and older: a 6-month prospective follow-up study.

BACKGROUND: Family support can help older adults better adhere to exercise routine, but it remains unclear whether an exercise program targeting older married couples would have stronger effects on exercise adherence than would a program for individuals. The purpose of this study was to determine the effects of an exercise program on the exercise adherence of older married couples over a 24-week follow-up period. METHODS: Thirty-four older married couples and 59 older adults participated in this study as couple and non-couple groups (CG and NCG, respectively). All participants attended an 8-week supervised program (once a week and a home-based exercise program comprising walking and strength exercises) and then participated in a follow-up measurement (24 weeks after post-intervention measurement). Exercise adherence was prospectively measured via an exercise habituation diary during the follow-up period-specifically, we asked them to record practice rates for walking (≥2 days/week) and strength exercises (≥6 items for 2 days/week). A multivariate logistic regression analysis was conducted to obtain the CG's odds ratios (ORs) and 95% confidence intervals (CIs) for adherence to walking and strength exercise adjusted for potential confounders (with NCG as the reference). RESULTS: Although the adherence rate of walking exercise in the CG was significantly higher than that in the NCG (29.2%; P < 0.001), there was no significant difference in the adherence rate of strength exercise between the two groups (P = 0.199). The multivariate logistic regression analysis showed that CG had significantly higher odds of adherence to walking exercise compared with the NCG (3.68 [1.57-8.60]). However, the odds of adherence to strength exercise did not significantly differ between the two groups (1.30 [0.52-3.26]). CONCLUSIONS: These results suggest that an exercise program targeting older married couples may be a useful strategy for maintaining walking adherence, even six months after the supervised program has ceased. A blinded randomized controlled trial will be needed to confirm this conclusion. TRIAL REGISTRATION: Retrospectively registered. UMIN Clinical Trials Registry (Registered: 02/11/16) UMIN000024689 .

FEN1 participates in repair of the 5'-phosphotyrosyl terminus of DNA single-strand breaks.

Etoposide is a widely used anticancer drug and a DNA topoisomerase II (Top2) inhibitor. Etoposide produces Top2-attached single-strand breaks (Top2-SSB complex) and double-strand breaks (Top2-DSB complex) that are thought to induce cell death in tumor cells. The Top2-SSB complex is more abundant than the Top2-DSB complex. Human tyrosyl-DNA phosphodiesterase 2 (TDP2) is required for efficient repair of Top2-DSB complexes. However, the identities of the proteins involved in the repair of Top2-SSB complexes are unknown, although yeast genetic data indicate that 5' to 3' structure-specific DNA endonuclease activity is required for alternative repair of Top2 DNA damage. In this study, we purified a flap endonuclease 1 (FEN1) and xeroderma pigmentosum group G protein (XPG) in the 5' to 3' structure-specific DNA endonuclease family and synthesized single-strand break DNA substrates containing a 5'-phoshotyrosyl bond, mimicking the Top2-SSB complex. We found that FEN1 and XPG did not remove the 5'-phoshotyrosyl bond-containing DSB substrates but removed the 5'-phoshotyrosyl bond-containing SSB substrates. Under DNA repair conditions, FEN1 efficiently repaired the 5'-phoshotyrosyl bond-containing SSB substrates in the presence of DNA ligase and DNA polymerase. Therefore, FEN1 may play an important role in the repair of Top2-SSB complexes in etoposide-treated cells.

Moderate to vigorous physical activity volume is an important factor for managing nonalcoholic fatty liver disease: a retrospective study.

UNLABELLED: Recently, the beneficial effects of increased physical activity (PA) on nonalcoholic fatty liver disease (NAFLD) in obese subjects were reported. However, the optimal strength and volume of PA in lifestyle modification to improve NAFLD pathophysiology and be recommended as an appropriate management of this condition are unclear. The primary goal of this retrospective study was to estimate the beneficial effects of a varying volume of moderate to vigorous intensity PA (MVPA) on the improvement of NAFLD. A total of 169 obese, middle-aged men were enrolled in a 12-week weight reduction program through lifestyle modification consisting of dietary restrictions plus aerobic exercise. Among these obese subjects, 40 performed MVPA for <150 min·wk(-1) , 42 performed MVPA for 150-250 min·wk(-1) , and 87 performed MVPA for >250 min·wk(-1) . The subjects in the MVPA ≥250 min·wk(-1) group, in comparison with those in the MVPA <250 min·wk(-1) group, showed significantly attenuated levels of hepatic steatosis (-31.8% versus -23.2%). This attenuation was likely independent of the detectable weight reduction. MVPA for ≥250 min·wk(-1) in comparison with that for <150 min·wk(-1) led to a significant decrease in the abdominal visceral adipose tissue severity (-40.6% versus -12.9%), levels of ferritin (-13.6% versus +1.5%), and lipid peroxidation (-15.1% versus -2.8%), and a significant increase in the adiponectin levels (+17.1% versus +5.6%). In association with these changes, the gene expression levels of sterol regulatory element-binding protein-1c and carnitine palmitoyltransferase-1 in peripheral blood mononuclear cells also significantly decreased and increased, respectively. CONCLUSION: MVPA for ≥250 min·wk(-1) as part of lifestyle management improves NAFLD pathophysiology in obese men. The benefits seem to be acquired through reducing inflammation and oxidative stress levels and altering fatty acid metabolism.