Decreased Abundance of Genus Slackia in Individuals With Obesity and Colorectal Adenoma.

Background and Aims: The increasing prevalence of obesity has significantly contributed to the global burden of colorectal cancer and the precancerous colorectal adenoma (CRA). Gut microbiota vary at each stage of colorectal carcinogenesis and participate in energy homeostasis. Elucidating gut microbiotal characteristics in obesity-related CRA may help prevent and treat colorectal tumors; however, this remains unclarified. Therefore, this study investigated the gut microbiota profile of patients with obesity-related CRA. Methods: This hospital setting-based cross-sectional study included 113 participants (66 [without CRA control group] and 37 [with CRA group]; each group was divided into obese and nonobese groups) who underwent screening colonoscopy between June 2019 and January 2020. Gut microbiota were analyzed using 16S rRNA and polymerase chain reaction techniques and the data compared between the aforementioned groups. Results: No between-group difference was observed in the diversity index; however, α diversity was the lowest in the obese CRA group. The CRA group had significantly higher and lower numbers of 26 and 17 genera, respectively. Genus Slackia was significantly lower in the obese CRA group than in the nonobese CRA group. Multivariate analysis of the quartiles according to genus Slackia relative abundance rates revealed that the first quartile was an independent risk factor for CRA (odds ratio, 3.57; 95% confidence interval 1.19-10.7). The proportion of equol reductase-positive participants was lowest in the obese CRA group (P = .04). Multivariate odds ratio for CRA was 5.46 (95% confidence interval 1.35-22.0) for genus Slackia and equol reductase-negative participants. Conclusion: Decreased abundance of genus Slackia and absence of equol reductase potentially influence obesity-related CRA development.

Correlation between plasma glutamate and adiponectin in patients with type 2 diabetes.

Visceral fat accumulation is a major determinant of type 2 diabetes mellitus and cardiovascular diseases. Recent studies have reported that glutamate is the most elevated amino acid in the plasma amino acid profile in patients with obesity and/or visceral fat accumulation. Here, we show the relationship between plasma glutamate and the clinical features of patients with type 2 diabetes. The study subjects were 62 (28 men and 34 women) Japanese patients with type 2 diabetes. Blood profiles, including glutamate and adiponectin (APN) levels and estimated visceral fat area (eVFA), were measured. We also evaluated the plasma amino acid levels in mice with or without obesity by GC/MS analysis. In patients with type 2 diabetes, plasma glutamate was positively correlated with BMI, eVFA, and fasting insulin but negatively correlated with APN and duration of diabetes. Additionally, multiple regression analysis revealed that plasma glutamate was a significant determinant of APN. The plasma glutamate level was most significantly increased in obese mice compared to control mice, and it was negatively correlated with APN. These results suggest that the level of plasma glutamate could be a strong indicator of adipocyte dysfunction in patients with type 2 diabetes.

Associations of oxidative balance score with total abdominal fat mass and visceral adipose tissue mass percentages among young and middle-aged adults: findings from NHANES 2011-2018.

Objective: This study aimed to explore the association of the oxidative balance score (OBS) with total abdominal fat mass (TAFM) and visceral adipose tissue mass (VATM) percentages among young and middle-aged U.S. adults. Methods: Young and middle-aged adults in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 were included. Analysis of variance and Rao-Scott adjusted chi-square tests were used to compare the characteristics across quartiles of OBS. Univariate and multivariate weighted logistic regression models were employed to explore the relationship between OBS and the risks of high TAFM or high VATM percentage in the general population and subgroups, while the interaction effects were tested with a likelihood test. Weighted restricted cubic spline analyses were utilized to assess the non-linear association of OBS with TAFM and VATM percentages. Results: The final sample included 8,734 young and middle-aged non-institutionalized U.S. adults representing 134.7 million adults. Compared with adults in the first quartile of OBS, those with higher OBS were less likely to have a high TAFM percentage; the ORs and 95% CI for adults in the second, third, and highest quartiles of OBS were 0.70 (0.53-0.94), 0.49 (0.36-0.60), and 0.25 (0.18-0.36), respectively. Similar trends were observed in the association between OBS and VATM percentages. Moreover, similar effects were confirmed in the sensitivity analyses and subgroup analyses according to demographic characteristics. Regarding the OBS subclass, higher dietary OBS and lifestyle OBS were also correlated with decreased ORs of high TAFM and VATM percentages. Conclusion: This study strongly suggests that higher OBS, as well as higher dietary OBS and lifestyle OBS, are significantly correlated with lower risks of abdominal obesity and visceral fat accumulation. The findings highlight the importance of an antioxidant-rich diet and maintaining a healthy lifestyle in reducing the risks.

Factors associated with the progression of myosteatosis in patients with cirrhosis.

OBJECTIVES: The presence of myosteatosis is one factor associated with poor prognosis for patients with cirrhosis; however, the factors contributing to worsening myosteatosis are, to our knowledge, unknown. The aim of this study was to clarify the changes in myosteatosis, and the factors involved in these changes. METHODS: The present study enrolled 178 patients with cirrhosis who underwent computed tomography twice to measure changes in skeletal muscle attenuation (SMA) at the L3 level. Factors associated with SMA and those associated with changes in SMA were examined. RESULTS: Using linear multiple regression analysis, age (ß = -0.22), skeletal muscle index (SMI; skeletal muscle area divided by height squared; ß = 0.25), and visceral and subcutaneous fat indices (VFI and SFI; the visceral and subcutaneous fat areas at the umbilical level divided by height squared; ß = -0.08, ß = -0.06, respectively) were identified as associated with SMA. The 100-d change in SMA was -0.21 ± 1.29 Hounsfield units (HU). Changes in SMI and SMA were positively associated (R = 0.183, P = 0.014), whereas those in VFI and SMA were negatively associated (R = -0.172, P = 0.022). No association was noted between the 100-d changes in SFI and SMA. In patients whose SMI increased and VFI decreased, the 100-d change in SMA was 0.24 ± 1.82 HU, which was marginally different from that in patients whose SMI decreased and VFI increased (-0.44 ± 1.32 HU, P = 0.077). CONCLUSIONS: In patients with cirrhosis, myosteatosis progressed, and decreases in SMI and increases in VFI were correlated with its progression.

A body shape index could serve to identify individuals with metabolic syndrome and increased arterial stiffness in the middle-aged population.

BACKGROUND: A body shape index (ABSI) is a novel anthropometric measure calculated using waist circumference (WC), body mass index (BMI), and body height. This study investigated the usefulness of ABSI to identify individuals with metabolic syndrome (MetS) and increased arterial stiffness in the middle-aged population. METHODS: Middle-aged workers who underwent periodic health check-ups and who were without previous cardiovascular events were enrolled (n = 10,182). In addition to ABSI, visceral fat area (VFA) was evaluated using computed tomography. Obesity and MetS were diagnosed on the basis of WC, VFA, and ABSI. Arterial stiffness was examined by measuring the cardio-ankle vascular index (CAVI). RESULTS: ABSI was significantly associated with CAVI in multivariable regression analysis. Logistic regression analysis revealed that ABSI was independently associated with the presence of MetS diagnosed on the basis of WC or VFA after adjustment for potential confounders, including BMI. Subjects with MetS diagnosed on the basis of each obesity index showed higher CAVI values than those without. Among subjects with MetS diagnosed on the basis of WC or VFA, those with MetS who met the definition of ABSI obesity showed significantly higher CAVI than those who did not. The other logistic regression analysis demonstrated that CAVI was independently associated with MetS defined on the basis of ABSI. CONCLUSIONS: ABSI was significantly associated with CAVI and the presence of MetS in the middle-aged population and helped to discriminate individuals with MetS and increased CAVI. ABSI could serve to identify individuals with MetS and increased arterial stiffness.

Visceral Fat Area by Abdominal Bioelectrical Impedance Analysis as a Risk of Obstructive Sleep Apnea.

This is the first study to evaluate directly visceral fat area (VFA) using a visceral fat (VF) meter by the abdominal bioelectrical impedance analysis (A-BIA) method in obstructive sleep apnea (OSA) patients diagnosed with polysomnography (PSG). The purpose of this study is to clarify (1) whether VFA measurement using a VF meter by the A-BIA method is possible even in a private clinic without burdening patients and staff and (2) how much VFA affects OSA compared to body mass index (BMI). Even without a computed tomography scan, which is the gold standard for VFA measurement, a VF meter could analyze patients by the A-BIA method and easily measure VFA. Therefore, it could be used safely even in a private sleep clinic, with very little burden on the patients and the medical staff. We investigated the association between OSA and VFA in 133 OSA patients. Multiple regression analysis revealed that VFA (ß = 0.28; P = 0.020) was a stronger coexisting factor for OSA than age, male gender, or BMI (ß = 0.26; P = 0.032) in all OSA patients. In the OSA patients with VF accumulation, only VFA was a significant component of OSA severity (ß = 0.36; P = 0.006). The A-BIA method instrument could become a useful device for the evaluation of VF accumulation in OSA patients in private sleep clinics. VF accumulation should be recognized as an important risk factor as well as a known risk factor for OSA.

The Association of Body Composition Parameters and Simultaneously Measured Inter-Arm Systolic Blood Pressure Differences.

Background and Objectives: An inter-arm systolic blood pressure difference (IASBPD) is defined as a blood pressure (BP) disparity of ≥10 mmHg between arms. IASBPDs are associated with an increased risk of cardiovascular disease (CVD). Similarly, visceral fat accumulation (VFA) is clinically important because it is associated with higher cardiovascular disease risk. Accordingly, this study compared the body composition parameters of IASBPD individuals with individuals who did not express an IASBPD. Materials and Methods: The analysis included 104 patients. The blood pressures of all participants were measured simultaneously in both arms using automated oscillometric devices. Then patients were divided into two groups according to their IASBPD status: Group 1 (IASBPD- (<10 mmHg)); Group 2 (IASPPD+ (≥10 mmHg)). Body composition parameters were measured using bioelectrical impedance analysis. Results: In 42 (40%) patients, the simultaneously measured IASBPD was equal to or higher than 10 mmHg. The right brachial SBP was higher in 63% of patients. There were no differences between the groups in terms of demographic and clinical characteristics. Regarding the two groups' body composition parameter differences, VFA was significantly higher in group 2 (p = 0.014). Conclusions: The IASBPD is known to be associated with an increased risk of cardiovascular events. Although the body mass indexes (BMIs) of the two groups were similar, VFA levels in those with a greater than 10 mmHg IASBPD were found to be significantly higher. This finding may explain the increased cardiovascular risk in this group.

Impact of visceral fat accumulation on the prognosis of patients with cirrhosis.

BACKGROUND & AIMS: The impact of obesity, evaluated using body mass index (BMI), on mortality in patients with cirrhosis is controversial. The prognostic impact of visceral fat accumulation, which is recommended as an indicator of obesity-related mortality, is still unknown. This study aimed to clarify the impact of visceral fat accumulation on mortality in patients with cirrhosis. METHODS: A total of 335 cirrhotic patients without hepatocellular carcinoma were retrospectively evaluated. The impact of obesity, defined as a visceral fat area ≥100 cm2 at the umbilical level or BMI ≥25 kg/m2 on mortality, was evaluated using competing risk analysis. RESULTS: Of 355 patients, visceral fat accumulation was seen in 147 patients. During the observation period (1340 ± 980 days), 84 patients died, and 17 received liver transplantation. Visceral fat accumulation was not found to be associated with mortality (hazard ratio [HR] 1.423, P = 0.180) in any of the patients. After stratification of the patients, visceral fat accumulation was observed to be associated with a poor prognosis in patients with skeletal muscle depletion (HR 3.804, P = 0.003), but not in those without (HR 1.147, P = 0.660). On the other hand, obesity defined by BMI ≥25 kg/m2 was not found to be associated with mortality in patients with (HR 0.341, P = 0.390) or without skeletal muscle depletion (HR 1.227, P = 0.500). CONCLUSIONS: Visceral fat accumulation is a useful index for evaluating obesity and aggravates mortality in cirrhotic patients with skeletal muscle depletion, but not in those without.

The 1975 type Japanese diet improves the gut microbial flora and inhibits visceral fat accumulation in mice.

In this study, the 1975 type Japanese diet was prepared and its effects and related mechanism were examined in mice. Mice were assigned to three experimental groups, the CD group fed a control diet, the MD group fed a modern Japanese diet (MD), and the JD group fed the 1975 type Japanese diet (JD) for 4 weeks. MD and JD were low protein, high fat, and high carbohydrate diets compared to the CD. Total white adipose tissue weights were significantly increased in the MD group compared to those in the CD group and were decreased in the JD group compared to those in the MD group. In the JD group, adipocyte hypertrophy was inhibited and Hsl mRNA expression was enhanced in epididymal adipose tissue and the number of bacteria associated with the production of short chain fatty acids was increased. Therefore, the JD inhibits lipid accumulation in white adipose tissue. ABBREVIATIONS: Actb: ß-actin; ALT: alanine aminotransferase; ANOVA: analyses of variance; AST: aspartate aminotransferase; Fas: fatty acid synthase; G6pdx: glucose 6-phosphate dehydrogenase; HE: hematoxylin and eosin; HOMA-IR: Homeostatic model assessment for insulin resistance; Hsl: hormone-sensitive lipase; JD: 1975 type Japanese diet; Leptin: leptin; MD: modern Japanese diet; Me: malic enzyme; NEFA: non-esterified fatty acids; PL: phospholipids; Pparδ: peroxisome proliferator-activated receptor delta; Pparγ: peroxisome proliferator-activated receptor gamma; qRT-PCR: quantitative reverse transcriptase polymerase chain reaction; SAMP8: senescence-accelerated prone 8; SEM: standard error of the mean; Srebp1c: Sterol regulatory element binding protein 1c; TBARS: thiobarbituric acid reactive substance; TC: total cholesterol; TG: Triacylglycerol; V3: variable regions 3.

Ganoderma lucidum culture supplement ameliorates dyslipidemia and reduces visceral fat accumulation in type 2 diabetic rats.

Diabetic rats were daily fed with a high-cholesterol diet containing 1% or 3% freeze-dried whole submerged G. lucidum culture or its mycelia for 5 weeks. Body weight, adipose tissue weight and plasma triglyceride levels were reduced, while high-density lipoprotein-cholesterol levels were elevated in rats fed with G. lucidum powder supplement diets. Notably, G. lucidum supplements downregulated the activities of hepatic acetyl-CoA carboxylase, fatty acid synthase and lipoprotein lipase, but upregulated the activity of hormone-sensitive lipase in the perirenal adipose tissues. Moreover, G. lucidum supplements increased the faecal triglyceride excretion. Therefore, daily supplementation of submerged G. lucidum culture, especially mycelia, can ameliorate dyslipidemia and reduce visceral fat accumulation in diabetic rats fed with a high-fat diet, which is closely related to the modulation of lipid synthesis, metabolism, and excretion.

Population Approaches Targeting Metabolic Syndrome Focusing on Japanese Trials.

The clinical importance of assessment of metabolic syndrome lies in the selection of individuals with multiple risk factors based on visceral fat accumulation, and helping them to reduce visceral fat. Behavioral modification by population approach is important, which adds support to the personal approach. The complexity of visceral fat accumulation requires multicomponent and multilevel intervention. Preparation of food and physical environments could be useful strategies for city planners. Furthermore, actions on various frameworks, including organizational, community, and policy levels, have been recently reported. There are universal public health screening programs and post-screening health educational systems in Japan, and diseases management programs in Germany. Understanding one's own health status is important for motivation for lifestyle modification. The U.S. Preventive Services Task Force recommends that primary care practitioners screen all adults for obesity and offer behavioral interventions and intensive counseling. Established evidence-based guidelines for behavioral counseling are needed within the primary care setting.

Miso (Fermented Soybean Paste) Suppresses Visceral Fat Accumulation in Mice, Especially in Combination with Exercise.

We investigated whether the difference in miso consumption between the Japanese diets of 1975 and 2010 has influenced the observed increase in diet-induced obesity. To recreate the 2010 and 1975 Japanese high-fat diets with the corresponding proportions of miso, freeze-dried miso was added to high-fat mouse feed at 1.6% and 2.6%, respectively. When 5-week-old male Institute of Cancer Research (ICR) mice were provided each of these diets ad libitum for 8 weeks, it was found that the white adipose tissue weight and adipocyte area were lower in mice receiving the 1975 diet than in those receiving the 2010 diet. Therefore, high miso consumption is one reason why the 1975 Japanese diet tended to not lead to obesity. Next, the combined effects of treadmill exercise and miso consumption were investigated. The mice were divided into three groups, which were provided either a high-fat diet (group C), a high-fat diet with exercise (group C + E), or a miso-supplemented high-fat diet with exercise (group M + E) for 8 weeks. In this experiment, the white adipose tissue weight and adipocyte area in group M + E were lower than in group C. When the mRNA expression of lipid metabolism-associated genes in adipose tissue was measured, we found that expression of Hsl (lipase, hormone sensitive), which is involved in lipolysis, and Pparγ (peroxisome proliferator activated receptor gamma), which regulates adipocyte differentiation upstream of Hsl, was increased in group M + E. These results clearly demonstrated that lipid accumulation in the adipose tissues is suppressed by miso consumption in combination with exercise.

Involvement of PPARγ/FSP27 in the pathogenic mechanism underlying insulin resistance: tipping the balance between lipogenesis and fat storage in adult catch-up growth rats.

BACKGROUND: Catch-up growth in adult (CUGA) is characterized by visceral fat accumulation, ectopic lipid deposition and insulin resistance (IR). Here, we investigated the determinants of these pathophysiological consequences of CUGA. METHODS: Rats were divided into different groups: control rats were offered normal chow ad libitum (AL), while experimental rats were put on 4-week caloric restriction (CR) initially, followed by regaining weight-matched normal chow (RN) in the RN group. General characteristics of lipid metabolism, expression level of genes in visceral adipose tissue (VAT), and glucose infusion rate (GIR60-120) by the hyperinsulinemic-euglycemic clamp were examined. RESULTS: After CR, percentage of abdominal fat mass (AFM%) was lower in the RN group than in the AL group but no difference was observed in serum non-esterified fatty acid (NEFA). Expression of fat-specific protein 27 (FSP27) was decreased in the RN group, while the expression of peroxisome proliferator-activated receptors γ (PPARγ), the key lipogenic gene, was increased. After refeeding, AFM% increased over time and serum NEFA persistently elevated in the RN group. Ectopic triglyceride contents were increased whereas insulin sensitivity was impaired. The expression of FSP27 did not follow the increase in the expression of PPARγ. Additionally, we observed a sustained increase in the expression of ATGL and CGI-58 in VAT in the RN group compared with the AL group after CR and refeeding, and a persistent shift-to-the-left of adipocyte size distribution accompanied by enhanced lipogenesis during CUGA. CONCLUSION: The persistent CR-induced imbalance of lipogenesis/fat storage capacity might be responsible for the CUGA-associated metabolic disorders.

Visceral adiposity index is associated with increased urinary albumin excretion: A population-based study.

BACKGROUND: The effects of visceral fat accumulation on the renal damage have drawn much attention. We aimed to investigate the possible relationship between visceral adiposity and albuminuria. METHODS: We included information from a population-based study in 9473 subjects aged 40 years or older. As a novel and valid indicator for visceral adipose function, visceral adiposity index (VAI) was determined by gender-specific equations and calculated using simple anthropometric and functional parameters. Increased urinary albumin excretion was defined as albumin-to-creatinine ratio (ACR) 30 mg/g or greater. RESULTS: The prevalence rate of increased urinary albumin excretion was 6.6% in this population and gradually increased across VAI quartiles. Participants with higher VAI had elevated age, blood pressure, cholesterol, fasting insulin and decreased high density lipoprotein cholesterol and estimated glomerular filtration rate (eGFR) level. In multivariate logistic regression analysis, the adjusted odds ratios (ORs) of increased urinary albumin excretion for increasing VAI quartiles were 1.00 (reference), 1.29 (95% confidence intervals [CI] 0.94-1.76), 1.46 (95% CI 1.08-1.97) and 1.79 (95% CI 1.33-2.41). In subgroup analysis and after multiple adjustments, significant relation between VAI level and prevalent increased urinary albumin excretion was detected in women, younger subjects, non-obesity subjects, those without diabetes and those with eGFR ≥60 ml/min per 1.73 m2. CONCLUSION: Visceral fat accumulation evaluating by VAI is independently associated with increased urinary albumin excretion in middle-aged and elderly Chinese.

Low muscle quality in Japanese type 2 diabetic patients with visceral fat accumulation.

BACKGROUND: Although obesity-related type 2 diabetes mellitus (T2DM) and sarcopenia in the elderly have been increasing worldwide, the associations among visceral fat accumulation, skeletal muscle indices (mass, strength, and quality) and cardiovascular diseases in T2DM remain poorly investigated. METHODS: We enrolled 183 Japanese T2DM inpatients (126 men, 57 women; mean age 64.7 ± 12.6 years, ± SD). The estimated-visceral fat area (eVFA) and skeletal muscle mass were measured by each device using bioelectrical impedance analysis method. We also measured grip strength by dynamometer and motor nerve conduction velocity (MCV). We analyzed the difference in skeletal muscle indices between T2DM patients with and without visceral fat accumulation, and examined the impact of skeletal muscle indices on cardiovascular diseases in patients with visceral fat accumulation. RESULTS: The prevalence of sarcopenia defined by the Consensus of Asian Working Group for Sarcopenia and low skeletal muscle mass were both lower in the visceral fat accumulation (+) group than in (-) group. However, the prevalence of weak hand grip strength was similar in the visceral fat accumulation (-) and (+) groups, indicating that considerable patients with visceral fat accumulation had weak grip strength in spite of fair skeletal muscle mass. Muscle quality [grip strength (kg)/arm muscle mass (kg)] was significantly lower in patients with visceral fat accumulation. Multiple regression analysis identified eVFA, MCV and sex as significant and independent determinants of muscle quality. In visceral fat accumulation (+) group, the patients with low muscle quality had longer duration of diabetes, lower eGFR, higher serum adiponectin, lower MCV and higher prevalence of cardiovascular diseases, compared to the patients with high muscle quality. Finally, sex- and age-adjusted models showed significant association between low muscle quality and cardiovascular diseases in all subjects (odds ratio 2.28, p = 0.012), especially in patients with visceral fat accumulation (odds ratio 2.72, p = 0.018). CONCLUSIONS: T2DM patients with visceral fat accumulation had low muscle quality, and patients with low muscle quality were more affected with cardiovascular diseases.

Contribution of maternal diabetes to visceral fat accumulation in offspring.

BACKGROUND/OBJECTIVES: Genetic and epidemiological studies provide evidence supporting the contribution of a genetic background of diabetes to the development of obesity and further suggest differences in the metabolic and cardiovascular risks between offspring with a paternal versus maternal family history of diabetes (FHD). The goal of this study was to explore the contribution of a parental FHD to visceral fat area (VFA). SUBJECTS/METHODS: This study enrolled 1875 subjects with normal glucose tolerance (age range: 20-78 years). VFA was assessed with magnetic resonance imaging. RESULTS: The study population consisted of 1573 subjects without a FHD, 115 subjects with a paternal FHD, and 187 subjects with a maternal FHD. For both genders, VFA was greater in offspring with a maternal FHD compared with those without a FHD (both P<0.05). For both genders, only VFA was an independent factor associated with a maternal FHD (both P<0.01). Compared with those without a FHD, men and women with a maternal FHD, but not those with a paternal FHD, were more likely to develop abdominal obesity (both P<0.05). After adjustment for independent factors related to VFA, VFA was increased by 9.60cm2 (standardized ß=0.069, P=0.012) and 4.57cm2 (standardized ß=0.056, P=0.007) in men and women with a maternal FHD, respectively. CONCLUSION: A maternal FHD contributed to visceral fat accumulation independently in both genders. Maternal transmission had a pronounced effect on obesity and related cardiovascular risk factors.

Fermented Soybean Suppresses Visceral Fat Accumulation in Mice.

SCOPE: Mice are fed a soybean diet before or after fermentation in the present work to allow direct comparison of the antiobesity effect of fermentation. METHODS: C57BL6J mice were fed high-fat diets containing boiled soybeans (prefermentation) or Natto (postfermentation) for 4 weeks. Prefermented cooked soybeans or Natto was added at levels of 2.5 and 5%, which are the amounts that can be ingested in a normal diet once and twice a day. In addition, mice gut microbiota from fecal samples were analyzed to explore the mechanisms of effects caused by fermentation. RESULTS: Natto intake significantly reduced visceral fat in a dose-dependent manner, inhibited hypertrophy of adipocytes, improved carbohydrate metabolism, and reduced oxidative stress. These effects were seen in mice fed soybeans before fermentation, but were stronger in mice fed Natto. Therefore, soybean intake has beneficial effects and fermentation of soybeans enhances these effects. Natto was found to suppress fatty acid synthesis and promote fatty acid catabolism in the liver. These effects were also stronger with Natto compared with soybeans before fermentation. In addition, Natto had more potent beneficial effects on gut microbiota compared to soybeans. CONCLUSIONS: These results suggest that Natto intake supports maintenance of health.

Association of serum fibroblast growth factor 19 levels with visceral fat accumulation is independent of glucose tolerance status.

BACKGROUND AND AIMS: Recent studies suggested that circulating fibroblast growth factor (FGF) 19 levels might be associated with the fat content and distribution, and varied with different glucose tolerance status. This study aimed to investigate the association of serum FGF19 levels with obesity and visceral fat accumulation in a Chinese population with differing glucose tolerance status. METHODS AND RESULTS: The 2383 participants were divided into subgroups of glucose tolerance status: normal glucose tolerance (NGT, n = 1754), impaired glucose regulation (IGR, n = 499), and newly diagnosed diabetes mellitus (DM, n = 130). They were further stratified into quartiles of serum FGF19 levels (Q1-Q4). Visceral fat area (VFA) and subcutaneous fat area were measured using magnetic resonance imaging. FGF19 were detected via quantitative sandwich enzyme-linked immunosorbent assay. Serum FGF19 levels showed a downtrend across the NGT, IGR, and DM groups (P for trend = 0.016). VFA was an independent and negative factor of serum FGF19 levels (standardized ß = -0.108, P = 0.001). After adjustment for glucose tolerance status, VFA differed significantly among FGF19 quartiles (P < 0.001), showing a downtrend from Q1-Q4. The associations of serum FGF19 levels and glucose tolerance status with VFA were independent of each other. After adjustment for insulin resistance and secretory function separately, VFA still decreased significantly from Q1-Q4 (all P < 0.001). CONCLUSION: Serum FGF19 levels were related to visceral fat accumulation. Independent of glucose tolerance status, serum FGF19 levels were inversely associated with VFA.

Visceral-to-subcutaneous fat ratio is independently related to small and large cerebrovascular lesions even in healthy subjects.

BACKGROUND AND AIMS: The severity of obesity is evaluated by visceral-to-subcutaneous fat ratio (VS ratio), which may be useful for predicting atherosclerosis. However, it is unclear how VS ratio affects different types of cerebrovascular lesions. This study was conducted to evaluate the clinical impact of visceral fat accumulation on the cerebrovascular lesions. METHODS: This cross-sectional study included 980 apparently healthy Japanese adults who underwent a health check-up program focused toward atherosclerosis, between 2011 and 2014. Visceral and subcutaneous fat accumulation was measured using abdominal computed tomography, and its relation to cerebrovascular disease was surveyed. RESULTS: Visceral and subcutaneous fat accumulation was 88 ± 50 cm2 and 141 ± 77 cm2, respectively. VS ratio was 0.69 ± 0.38. Intimal thickening in the carotid arteries was detected in 849 cases (86.6%) and stenosis was observed in seven (0.7%). Brain magnetic resonance imaging showed white matter hyperintensities regarded as ischemic changes in 196 subjects (20.0%). Multiple logistic regression analysis adjusted for age, gender, diabetes mellitus, dyslipidemia, hypertension, and hyperuricemia showed that a 0.1 increase in VS ratio was related to the presence of ischemic changes [odds ratio (OR): 1.05, 95% CI: 1.01-1.10, p = 0.009], cerebral artery stenosis or occlusion (OR: 1.14, 95% CI: 1.03-1.25, p = 0.007), and cervical plaque (OR: 1.09, 95% CI: 1.05-1.13, p < 0.001). CONCLUSIONS: VS ratio was independently associated with both large and small vessel lesions in apparently healthy subjects.

MAP4K4 and IL-6+ Th17 cells play important roles in non-obese type 2 diabetes.

Obesity is a causal factor of type 2 diabetes (T2D); however, people without obesity (including lean, normal weight, or overweight) may still develop T2D. Non-obese T2D is prevalent in Asia and also frequently occurs in Europe. Recently, multiple evidences oppose the notion that either obesity or central obesity (visceral fat accumulation) promotes non-obese T2D. Several factors such as inflammation and environmental factors contribute to non-obese T2D. According to the data derived from gene knockout mice and T2D clinical samples in Asia and Europe, the pathogenesis of non-obese T2D has been unveiled recently. MAP4K4 downregulation in T cells results in enhancement of the IL-6+ Th17 cell population, leading to insulin resistance and T2D in both human and mice. Moreover, MAP4K4 single nucleotide polymorphisms and epigenetic changes are associated with T2D patients. Interactions between MAP4K4 gene variants and environmental factors may contribute to MAP4K4 attenuation in T cells, leading to non-obese T2D. Future investigations of the pathogenesis of non-obese T2D shall lead to development of precision medicine for non-obese T2D.