Muscle Quality as a Potential Diagnostic Marker of Advanced Liver Fibrosis in Patients with Non-alcoholic Fatty Liver Disease.

Background: Muscle-liver crosstalk plays an important role in the development and progression of non-alcoholic fatty liver disease (NAFLD). The measurement of muscle echo-intensity during ultrasonography is a real-time, non-invasive method of assessing muscle quality. In this retrospective study, we investigated the significance of poor muscle quality (namely, a greater mass of non-contractile tissue, including intramuscular fat) as a risk factor for advanced liver fibrosis and considered whether it may represent a useful tool for the diagnosis of advanced liver fibrosis. Methods: We analyzed data from 307 patients with NAFLD (143 men and 164 women) who visited the University of Tsukuba Hospital between 2017 and 2022. The patients were stratified into the following tertiles of muscle quality according to their muscle echo-intensity on ultrasonography: modest (84.1 A.U.), intermediate (97.4 A.U.), and poor (113.6 A.U.). We then investigated the relationships between muscle quality and risk factors for advanced liver fibrosis and calculated appropriate cutoff values. Results: Patients with poor muscle quality showed a significant, 7.6-fold greater risk of liver fibrosis compared to those with modest muscle quality. Receiver operating characteristic curve analysis showed that muscle quality assessment was as accurate as the Fibrosis-4 index and NAFLD fibrosis score in screening for liver fibrosis and superior to the assessment of muscle quantity and strength, respectively. Importantly, a muscle echo-intensity of ≥92.4 A.U. may represent a useful marker of advanced liver fibrosis. Conclusion: Muscle quality may represent a useful means of identifying advanced liver fibrosis, and its assessment may become a useful screening tool in daily practice.

Triglyceride-glucose index is capable of identifying metabolically obese, normal-weight older individuals.

BACKGROUND: The concept of metabolically obese, normal weight (MONW) has emerged to describe individuals with a normal body mass index (BMI) who are at a relatively high risk of chronic diseases. However, BMI itself is a suboptimal index for the assessment of the health risks associated with visceral fat. The triglyceride-glucose (TyG) index is considered to be a reliable and cost-effective marker of insulin resistance. Therefore, in the present study, we aimed to determine the TyG index cut-off values that could be used to define MONW in older people and to determine the usefulness of these values for the prediction of chronic diseases. METHODS: A total of 4,721 participants in the Korea National Health and Nutritional Examination Survey who were ≥ 60 years of age and did not have underweight or obesity were included. MONW was defined using the criteria for metabolic syndrome (MS), and the TyG index was calculated on the basis of the fasting plasma triglyceride and glucose concentrations. Chronic diseases, including T2DM, hypertension, and non-alcoholic fatty liver disease (NAFLD), were diagnosed. RESULTS: The prevalence of MS increased from the lowest to the highest TyG index tertile. The cut-off values of the TyG index for MONW were calculated as 8.88 and 8.80 for males and females, respectively. MONW, defined using these cut-off values, was associated with high odds ratios for NAFLD, T2DM, and hypertension in both males and females. CONCLUSIONS: The TyG index cut-off values calculated in the present study can be used to discriminate individuals with MONW from other older individuals without obesity and to predict the risk of chronic diseases. These findings show that the TyG index is an effective and cost-efficient method of assessing the risk of chronic diseases in people with MONW.

The Triglyceride-Glucose Index is Independently Associated with Chronic Kidney Disease in the Geriatric Population, Regardless of Obesity and Sex.

BACKGROUND: Insulin resistance (IR) negatively affects several risk factors of chronic kidney disease (CKD). This cross-sectional study investigated whether the triglyceride-glucose (TyG) index, which reflects IR, was independently associated with CKD in a geriatric population, regardless of obesity and sex. METHODS: The analysis included 7,326 individuals (2,864 males and 4,462 females) aged ≥60 years. Non-obesity or obesity was evaluated using a body mass index cutoff of 25 kg/m2. The TyG index was calculated as ln [triglyceride concentration (mg/dL)×fasting plasma glucose concentration (mg/dL)]/2. All participants were categorized into three groups according to TyG tertiles. Moderate-to-severe CKD (MSCKD) was defined as an estimated glomerular filtration rate (eGFR) of <45.0 mL/min/1.73 m2. RESULTS: In males and females with or without obesity, a trend test showed a decreasing tendency in the eGFR from the lowest to highest TyG tertiles. Males without obesity and females with obesity in the middle and highest tertiles of the TyG index were 2.342 and 2.393, and were 2.313 and 3.516 times more likely to have MSCKD, respectively. Those with or without obesity in the highest tertile of the TyG index were 1.736 and 2.374 times more likely to have MSCKD, respectively. CONCLUSION: Geriatric populations with an increased TyG index have a high risk of MSCKD regardless of obesity and sex. Our findings suggest that increased IR is associated with CKD in the geriatric population independent of obesity and sex.

Exercise Is Medicine for Nonalcoholic Fatty Liver Disease: Exploration of Putative Mechanisms.

Exercise remains a key component of nonalcoholic fatty liver disease (NAFLD) treatment. The mechanisms that underpin improvements in NAFLD remain the focus of much exploration in our attempt to better understand how exercise benefits patients with NAFLD. In this review, we summarize the available scientific literature in terms of mechanistic studies which explore the role of exercise training in modulating fatty acid metabolism, reducing hepatic inflammation, and improving liver fibrosis. This review highlights that beyond simple energy expenditure, the activation of key receptors and pathways may influence the degree of NAFLD-related improvements with some pathways being sensitive to exercise type, intensity, and volume. Importantly, each therapeutic target of exercise training in this review is also the focus of previous or ongoing drug development studies in patients with nonalcoholic steatohepatitis (NASH), and even when a regulatory-agency-approved drug comes to market, exercise will likely remain an integral component in the clinical management of patients with NAFLD and NASH.

Novel Approach for Glycemic Management Incorporating Vibration Stimulation of Skeletal Muscle in Obesity.

Because obesity is associated with impaired glucose tolerance and type 2 diabetes (T2D), it is important to manage the blood glucose level at an early stage. Nevertheless, people with obesity have significantly lower resistance to muscle fatigue after exercise and exercise adherence. Therefore, we developed a novel "Relaxing-Vibration Training (RVT)" consisting of 25 postures using vibration stimulation of skeletal muscle and determined the feasibility of RVT for glycemic management. Thirty-one participants with obesity were enrolled in a controlled trial (CT) and experimental trial (ET) based on a 75 g oral glucose tolerance test (OGTT). During the CT, participants were required to rest in a quiet room. During the ET, the RVT program (50 Hz, 4 mm), consisting of 25 postures of relaxation and stretching on the vibratory platform, was performed for 40 min. Subsequently, the participants rested as in the CT. Subjective fatigue and muscle stiffness measurements and blood collection were conducted before and after RVT. In both the CT and ET, interstitial fluid (ISF) glucose concentrations were measured every 15 min for 2 h. The incremental area under the curve value of real-time ISF glucose during an OGTT was significantly lower in the ET than in the CT (ET: 7476.5 ± 2974.9, CT: 8078.5 ± 3077.7, effect size r = 0.4). Additionally, the levels of metabolic glucose regulators associated with myokines, muscle stiffness, and subjective fatigue significantly improved after RVT. This novel RVT suggests that it is effective in glycemic management with great potential to improve impaired glucose tolerance and T2D with obesity in the future.

Triglyceride-Glucose Index as a Potential Indicator of Sarcopenic Obesity in Older People.

PURPOSE: This population-based cross-sectional study aimed to determine whether the triglyceride-glucose index (TyG index) is associated with sarcopenic obesity (SO) and whether it would be a helpful indicator of SO. METHODS: A total of 3821 participants aged ≥ 60 years were selected for the study group, and 4919 participants aged 20-39 years were included as a reference group. The participants were allocated to sarcopenia, obesity, and SO groups depending on if their body mass index (BMI) was ≥25 kg/m2 and their sarcopenia index was ≤1 standard deviation (SD) lower than the mean of the reference group. The sex-specific differences and trends among the participants were analyzed by using the TyG index tertiles, and appropriate cut-off values of the TyG index for SO were calculated. RESULTS: As the TyG index increased, BMI increased, but the sarcopenia index decreased in both sexes. Males and females in the middle and highest tertiles of the TyG index were 1.775 and 3.369, and they were 1.993 and 3.157 times more likely to have SO, respectively. The cut-off values of the TyG index for SO in males and females were ≥8.72 and 8.67, respectively. CONCLUSION: A high TyG index is positively associated with SO, and the TyG index may be considered a potential indicator of SO.

Use of the Visceral Adiposity Index as an Indicator of Chronic Kidney Disease in Older Adults: Comparison with Body Mass Index.

The visceral adiposity index (VAI) was recently introduced to quantify visceral fat accumulation and dysfunction. This cross-sectional study explored whether the VAI is associated with chronic kidney disease (CKD) in older adults and compared its utility with that of body mass index (BMI) for predicting CKD. In total, 7736 older adults (3479 men and 4257 women) aged ≥ 60 years were divided into normal, mild, and moderate-to-severe CKD groups. Associations of the VAI and BMI with CKD were compared among the groups, and cut-off points for moderate-to-severe CKD (MSCKD) were established. While the VAI could discriminate among all of the groups, the BMI could not. The severity of CKD was more strongly associated with the VAI than BMI. The odds ratios indicated that, in the fully adjusted model, the VAI was a significant predictor of MSCKD in both men and women, while the BMI was a significant predictor only in men. For the VAI, the area under the receiver operating characteristic curve values for men and women were 0.631 (cut-off point: ≥2.993) and 0.588 (≥4.001), compared with 0.555 (≥25.335) and 0.533 (≥24.096) for BMI, respectively. Taken together, the findings suggest that the VAI is associated with CKD and represents a better indicator for the disease than BMI.

The Anthropometric Measure 'A Body Shape Index' May Predict the Risk of Osteoporosis in Middle-Aged and Older Korean People.

A body shape index (ABSI) is a recently introduced index of abdominal adiposity, relative to body mass index and height, and represents an alternative to body mass index and waist circumference. We aimed to determine whether ABSI is associated with osteoporosis and the ability of ABSI to predict osteoporosis, to investigate the relationship between obesity and osteoporosis In total, 6717 Korean participants (3151 men and 3566 women; 63.6 ± 8.5 years) were recruited and placed into the Normal, Osteopenia, or Osteoporosis groups on the basis of the minimum T-scores of the lumbar spine, proximal femur, and femoral neck. The T-scores of each region and ABSI were compared among the groups and odds ratios and cut-off values of ABSI for osteoporosis were calculated. In participants of both sexes, ABSI tended to increase as bone health deteriorated. The men and women in the highest quartile of ABSI were 1.887 and 2.808 times more likely to have osteoporosis, respectively, and the potential ABSI cut-off values for osteoporosis were 0.0813 and 0.0874 for male and female participants, respectively. These findings suggest that augmentation of ABSI and obesity is associated with a higher risk of osteoporosis and that ABSI may predict the risk of osteoporosis.

The A Body Shape Index Might Be a Stronger Predictor of Chronic Kidney Disease Than BMI in a Senior Population.

The A Body Shape Index (ABSI) was recently introduced to quantify abdominal adiposity relative to the body mass index (BMI) and height. This cross-sectional study was performed to explore whether the ABSI is linked to chronic kidney disease (CKD) in older adults and compare the predictive capacity of the ABSI versus BMI for CKD. In total, 7053 people aged ≥ 60 years were divided into normal, mild, and moderate-to-severe CKD groups based on their estimated glomerular filtration rate (eGFR). The correlation of the ABSI with the eGFR and the differences and trends in the ABSI and BMI among the groups were analyzed, and the cutoff points for moderate-to-severe CKD were calculated. The association between the ABSI and CKD was stronger than that between the BMI and CKD. The ABSI had a better capacity to discriminate the CKD stage than did the BMI. The capacity of the ABSI to predict moderate-to-severe CKD was higher than that of the BMI and was more substantial in women than men. The ABSI cutoff points for CKD were ≥0.0822 and 0.0795 in men and women, respectively. In conclusion, the ABSI serves as a better index than the BMI for screening and detecting high-risk individuals with CKD.

Effect of a sulforaphane supplement on muscle soreness and damage induced by eccentric exercise in young adults: A pilot study.

OBJECTIVE: Excessive exercise increases the production of reactive oxygen species in skeletal muscles. Sulforaphane activates nuclear factor erythroid 2-related factor 2 (Nrf2) and induces a protective effect against oxidative stress. In a recent report, sulforaphane intake suppressed exercise-induced oxidative stress and muscle damage in mice. However, the effect of sulforaphane intake on delayed onset muscle soreness after eccentric exercise in humans is unknown. We evaluated the effect of sulforaphane supplement intake in humans regarding the delayed onset muscle soreness (DOMS) after eccentric exercise. RESEARCH METHODS & PROCEDURES: To determine the duration of sulforaphane supplementation, continuous blood sampling was performed and NQO1 mRNA expression levels were analyzed. Sixteen young men were randomly divided into sulforaphane and control groups. The sulforaphane group received sulforaphane supplements. Each group performed six set of five eccentric exercise with the nondominant arm in elbow flexion with 70% maximum voluntary contraction. We assessed muscle soreness in the biceps using the visual analog scale, range of motion (ROM), muscle damage markers, and oxidative stress marker (malondialdehyde; MDA). RESULTS: Sulforaphane supplement intake for 2 weeks increased NQO1 mRNA expression in peripheral blood mononuclear cells (PBMCs). Muscle soreness on palpation and ROM were significantly lower 2 days after exercise in the sulforaphane group compared with the control group. Serum MDA showed significantly lower levels 2 days after exercise in the sulforaphane group compared with the control group. CONCLUSION: Our findings suggest that sulforaphane intake from 2 weeks before to 4 days after the exercise increased NQO1, a target gene of Nrf2, and suppressed DOMS after 2 days of eccentric exercise.

Relationships of Dietary Habits and Physical Activity Status with Non-Alcoholic Fatty Liver Disease Featuring Advanced Fibrosis.

(1) Aim: Hepatic fibrosis is a prognostic factor for disease progression in non-alcoholic fatty liver disease (NAFLD). We aimed to determine the relationships between diet, physical activity, and the progression of liver fibrosis. (2) Methods: The 349 participants were categorized by their FibroScan-aspartate aminotransferase score, and they completed a questionnaire regarding their diet and physical activity. (3) Results: There were 233 patients in the negative-on-screening group, 78 in the gray zone group, and 38 in the positive-on-screening group. The frequencies of consumption of soybeans and soybean products and of light-colored vegetables were lower in the positive group; whereas the frequencies of consumption of snack food and fried sweets, jelly and pudding, fried food, and butter, lard, and beef tallow were higher. The odds ratios for the fibrosis progression in patients who consumed fried food ≥4 times/week was 2.21. The positive group also showed lower physical activity level (PAL) and exercise (Ex, metabolic equivalents for tasks (METs)/hour/week). The patients who undertook Ex at >7.5 had an odds ratio of 0.21 for the fibrosis progression. (4) Conclusion: High consumption of fried food and low Ex are risk factors for the fibrosis progression in NAFLD.

Prevention of non-alcoholic steatohepatitis by long-term exercise via the induction of phenotypic changes in Kupffer cells of hyperphagic obese mice.

Exercise ameliorates nonalcoholic fatty liver disease (NAFLD) by inducing phenotypic changes in Kupffer cells (KCs). p62/Sqstm1-knockout (p62-KO) mice develop NAFLD alongside hyperphagia-induced obesity. We evaluated (1) the effects of long-term exercise on the foreign-body phagocytic capacity of KCs, their surface marker expression, and the production of steroid hormones in p62-KO mice; and (2) whether long-term exercise prevented the development of non-alcoholic steatohepatitis (NASH) in p62-KO mice fed a high-fat diet (HFD). In experiment 1, 30-week-old male p62-KO mice were allocated to resting (p62-KO-Rest) or exercise (p62-KO-Ex) groups, and the latter performed long-term exercise over 4 weeks. Then, the phenotype of their KCs was compared to that of p62-KO-Rest and wild-type (WT) mice. In experiment 2, 5-week-old male p62-KO mice that were fed a HFD performed long-term exercise over 12 weeks. In experiment 1, the phagocytic capacity of KCs and the proportion of CD68-positive cells were lower in the p62-KO-Rest group than in the WT group, but they increased with long-term exercise. The percentage of CD11b-positive KCs was higher in the p62-KO-Rest group than in the WT group, but lower in the p62-KO-Ex group. The circulating dehydroepiandrosterone (DHEA) concentration was higher in p62-KO-Ex mice than in p62-KO-Rest mice. In experiment 2, the body mass and composition of the p62-KO-Rest and p62-KO-Ex groups were similar, but the hepatomegaly, hepatic inflammation, and fibrosis were less marked in p62-KO-Ex mice. The DHEA concentration was higher in p62-KO-Ex mice than in WT or p62-KO-Rest mice. Thus, long-term exercise restores the impaired phagocytic capacity of KCs in NAFLD obese mice, potentially through greater DHEA production, and prevents the development of NASH by ameliorating hepatic inflammation and fibrogenesis. These results suggest a molecular mechanism for the beneficial effect of exercise in the management of patients with NAFLD.

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.

Effects of Exercise on the Oral Microbiota and Saliva of Patients with Non-Alcoholic Fatty Liver Disease.

Exercise can be hypothesized to play an important role in non-alcoholic fatty liver disease (NAFLD) treatment by changing the oral bacterial flora and in the mechanism underlying periodontal disease. We performed salivary component analysis before and after an exercise regimen, and genome analysis of the oral bacterial flora to elucidate the underlying mechanism. Obese middle-aged men with NAFLD and periodontal disease were allocated to 12-week exercise (n = 49) or dietary restriction (n = 21) groups. We collected saliva to compare the oral microflora; performed predictive analysis of metagenomic functions; and, measured the salivary immunoglobulin A, cytokine, bacterial lipopolysaccharide (LPS), and lactoferrin concentrations. The exercise group showed improvements in the clinical indices of oral environment. Salivary component analysis revealed significant reductions in LPS, and lactoferrin during the exercise regimen. Diversity analysis of oral bacterial flora revealed higher alpha- and beta-diversity after the exercise regimen. Analysis of the microbial composition revealed that the numbers of Campylobacter (+83.9%), Corynebacterium (+142.3%), Actinomyces (+75.9%), and Lautropia (+172.9%) were significantly higher, and that of Prevotella (-28.3%) was significantly lower. The findings suggest that an exercise regimen improves the oral environment of NAFLD patients by increasing the diversity of the oral microflora and reducing the number of periodontal bacteria that produce LPS and its capability.

Relationships of Fat and Muscle Mass with Chronic Kidney Disease in Older Adults: A Cross-Sectional Pilot Study.

This cross-sectional pilot study aimed to assess the relationships of fat and muscle mass with chronic kidney disease (CKD) in older adults. Serum creatinine concentration was used to measure estimated glomerular filtration rate (mL/min/1.73 m2) in the 236 subjects, who were allocated to three groups: a normal (≥60.0), a mild CKD (45.0-59.9), and a moderate to severe CKD (<45.0) group. The Jonckheere-Terpstra test and multivariate logistic regression were employed to assess body composition trends and the relationships of % fat mass (FM) or % muscle mass index (MMI) with moderate-to-severe CKD. Body weight, fat-free mass, MMI, and %MMI tended to decrease with an increase in the severity of CKD, but the opposite trend was identified for %FM. No relationship with BMI was identified. The participants in the middle-high and highest quartile for %FM were 6.55 and 14.31 times more likely to have moderate to severe CKD. Conversely, the participants in the highest quartile for %MMI were 0.07 times less likely to have moderate to severe CKD. Thus, high fat and low muscle mass may be more strongly associated with CKD than obesity per se.

Cardiorespiratory fitness is strongly linked to metabolic syndrome among physical fitness components: a retrospective cross-sectional study.

BACKGROUND: Maintaining a good level of physical fitness from engaging in regular exercise is important for the treatment and prevention of metabolic syndrome (MetS). However, which components constitutive of physical fitness confer the greatest influence remains controversial. This retrospective cross-sectional study aimed to investigate the association between MetS and physical fitness components including cardiorespiratory fitness, muscle strength, flexibility, and agility and to identify which physical fitness components have the largest influence on MetS. METHODS: A total of 168 Japanese adult males aged 25-64 years were allocated into non-MetS, pre-MetS, and MetS groups according to the criteria recommended by the Japanese Society of Internal Medicine. Anthropometric measurement of body composition by whole-body dual-energy X-ray absorptiometry and measures related to MetS, including waist circumference, triglyceride level, high-density lipoprotein cholesterol level, blood pressure, glucose level, and physical fitness components, were assessed. For evaluation of cardiorespiratory fitness, muscle strength, flexibility, agility, and balance, maximal oxygen consumption (VO2peak) and oxygen uptake at anaerobic threshold (VO2AnT), handgrip strength and vertical jumping, trunk extension and flexion, stepping side to side, and single-leg balance task with the eyes closed were assessed, respectively. RESULTS: A progressive tendency of increasing body weight, body mass index, whole-body lean and fat mass, percentage of whole-body fat mass, trunk lean and fat mass, percentage of trunk fat mass, arm fat mass, waist circumference, triglyceride level, systolic and diastolic blood pressure, and blood glucose level from the non-MetS group to the MetS group was significant (P < 0.05). Conversely, the cardiorespiratory endurance parameters VO2peak and VO2AnT and the high-density lipoprotein cholesterol level showed a progressively decreasing tendency across the groups (P < 0.01). In addition, a VO2peak below 29.84 ml·kg·min-1 (P = 0.028) and VO2AnT below 15.89 ml·kg·min-1 (P = 0.011) were significant risk components for pre-MetS and MetS. However, there was no significant tendency with respect to muscle strength, agility, and flexibility. CONCLUSION: Cardiorespiratory fitness is strongly linked to metabolic syndrome among physical fitness components.

Clinical and anthropometric characteristics of non-obese non-alcoholic fatty liver disease subjects in Japan.

AIM: The underlying mechanism of non-obese non-alcoholic fatty liver disease (NAFLD) has not been fully elucidated. We classified patients with NAFLD by sex and body mass index and compared their clinical features to clarify the background pathophysiology of non-obese NAFLD. METHODS: A total of 404 patients with NAFLD were divided according to their body mass index (<25 [non-obese], 25 to <30 [obese], and ≥30 [severe obese]), and were further compared with 253 patients without obesity and NAFLD (non-NAFLD). RESULTS: The proportion of the individuals with non-obese NAFLD was 25.7% in men and 27.6% in women. The male and female non-obese NAFLD groups had lower skeletal muscle mass and muscle strength than the obese NAFLD groups. The visceral fat area, although low, was ≥100 cm2 in 59.3% of men and 43.8% of women. An increase in liver fat accumulation, hepatic fibrosis, homeostasis model assessment of insulin resistance, and leptin levels was modest in the non-obese NAFLD group compared with a marked increase in the obese NAFLD groups. The muscle mass of the non-obese NAFLD group was similar to that of the non-NAFLD group, but muscle steatosis was particularly common among women. Multivariate analysis revealed that the factors contributing to increased liver fat accumulation in the non-obese NAFLD group were visceral fat area, HbA1c, myostatin, and leptin. CONCLUSIONS: In patients with non-obese NAFLD, a sex difference was observed in the clinical features. In addition to increased visceral fat, decreased muscle mass and muscle strength, muscle atrophy (presarcopenia), and impaired glucose tolerance were considered to be important pathophysiological factors.

Urinary Levels of Titin-N Fragment, a Skeletal Muscle Damage Marker, are Increased in Subjects with Nonalcoholic Fatty Liver Disease.

Sarcopenia is a pathological condition affecting the development and progression of NAFLD. Urinary levels of titin-N fragment, a biomarker reflecting muscle damage, were measured in NAFLD subjects, and analyzed in a retrospective manner for possible correlations with NAFLD pathophysiology to assess their clinical relevance. This study enrolled 153 NAFLD subjects and 100 subjects without NAFLD, obesity or diabetes mellitus (non-NAFLD). NAFLD subjects had more decreased knee extension strength. NAFLD subjects had greater subcutaneous fat thickness and echo intensity (brightness) of the rectus femoris muscle on ultrasound images; higher levels of the intra- and extra-myocellular lipids (IMCL, EMCL) using 1H-MRS. Urinary titin-N fragment levels were increased with increasing age but not different between males and females. NAFLD subjects had higher titin-N fragment levels than non-NAFLD subjects. The levels were negatively correlated with skeletal muscle mass and knee extension strength and positively correlated with muscle echo intensity, EMCL, and liver fibrosis scores (NAFLD fibrosis score, FIB-4 index). Multivariate analysis revealed that factors affecting the levels were skeletal mass index, leg skeletal muscle mass, liver stiffness, and NAFLD fibrosis score. Urinary levels of titin-N fragment reflected skeletal muscle deterioration and functional decline, and was closely associated with hepatic pathological conditions in NAFLD subjects.