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Abstract Physical inactivity as well as breakfast skipping is known as risk factor for various metabolic diseases, such as obesity and type 2 diabetes. We have previously reported that a breakfast skipping model, in which the timing of feeding is delayed, induces abnormal lipid metabolism by altering the circadian rhythm of lipid metabolism-related genes in rats. The purpose of this study was to elucidate the synergistic effect of physical inactivity and breakfast skipping on lipid metabolism. We adopted sciatic neurectomized rats as physically inactive models, because we confirmed that the rats mildly decreased their spontaneous locomotor activity compared to sham-operated rats. And then the physically inactive model rats were fed a mild high-fat diet during zeitgeber time (ZT) 12–0 in the control group and ZT16–0 in the breakfast skipping group for 11 days. Body weight gain and total food intake were similar in both groups. Breakfast skipping induced a significant visceral fat accumulation, which was not observed in our previous breakfast skipping or physically inactive studies. The mRNA levels of clock and lipogenesis-related genes were altered by breakfast skipping in the liver and epididymal adipose tissue, and serum insulin level was altered by breakfast skipping. These results suggest that physical inactivity and breakfast skipping synergistically induces drastic visceral fat accumulation due to the alteration of circadian clock and lipid metabolism in the liver and adipose tissue. Therefore, regular feeding timing plays an important role in the health of a sedentary modern society.

Physical inactivity as well as breakfast skipping is known as risk factor for various metabolic diseases, such as obesity and type 2 diabetes. We have previously reported that a breakfast skipping model, in which the timing of feeding is delayed, induces abnormal lipid metabolism by altering the circadian rhythm of lipid metabolism-related genes in rats. The purpose of this study was to elucidate the synergistic effect of physical inactivity and breakfast skipping on lipid metabolism. We adopted sciatic neurectomized rats as physically inactive models, because we confirmed that the rats mildly decreased their spontaneous locomotor activity compared to sham-operated rats. And then the physically inactive model rats were fed a mild high-fat diet during zeitgeber time (ZT) 12–0 in the control group and ZT16–0 in the breakfast skipping group for 11 days. Body weight gain and total food intake were similar in both groups. Breakfast skipping induced a significant visceral fat accumulation, which was not observed in our previous breakfast skipping or physically inactive studies. The mRNA levels of clock and lipogenesis-related genes were altered by breakfast skipping in the liver and epididymal adipose tissue, and serum insulin level was altered by breakfast skipping. These results suggest that physical inactivity and breakfast skipping synergistically induces drastic visceral fat accumulation due to the alteration of circadian clock and lipid metabolism in the liver and adipose tissue. Therefore, regular feeding timing plays an important role in the health of a sedentary modern society. [ABSTRACT FROM AUTHOR]

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.

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.

ObjectiveThis 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.MethodsYoung 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.ResultsThe 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.ConclusionThis 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.

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.

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

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. Actb: β-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 To investigate the mechanism of effects of the 1975 type Japanese diet in humans, this study investigated variations in lipid metabolism and intestinal microflora in mice. [ABSTRACT FROM AUTHOR]

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., (© 2024 The Authors.)

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.

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− (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.

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. 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. 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. Visceral fat accumulation evaluating by VAI is independently associated with increased urinary albumin excretion in middle-aged and elderly Chinese. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Deng, Wu, Luo, Chen, Liu, Nie, Tao, Li, Luo and Xia.)

Highlights • This study enrolled a Chinese population with normal glucose tolerance. • Individuals with a maternal FHD were at higher risk for abdominal obesity. • A maternal FHD was positively and independently associated with VFA. • Maternal transmission of visceral fat accumulation was more pronounced. Abstract 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 9.60 cm2 (standardized β = 0.069, P = 0.012) and 4.57 cm2 (standardized β = 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. [ABSTRACT FROM AUTHOR]

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 β = -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. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the effect of young barley grass extract powder on body weight increase and visceral fat accumulation in mice fed a high-fat diet. Methods: Young barley grass extract powder was manufactured by freeze drying the compressed juice. Mice (6 weeks of age) were fed a high-fat diet or a high-fat diet that included 1% barley grass extract powder for 8 weeks. Body weights were monitored for 8 weeks and visceral fat accumulation was measured after 8 weeks. Results: Young barley grass extract powder significantly reduced body weight increases and visceral fat accumulation in mice fed a high-fat diet. Conclusion: Long-term consumption of young barley grass extract powder may be effective for the prevention of metabolic syndromes such as obesity, atherosclerosis, and diabetes. [ABSTRACT FROM AUTHOR]

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 cm 2 and 141 ± 77 cm 2 , 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. [ABSTRACT FROM AUTHOR]

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 nonobese 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. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the use of the FINDRISC score in an overweight and obese population to predict glucose status.Methods: In 651 overweight/obese subjects (M/F: 193/458, age 43±13 y, BMI 38.2±6.1kg/m(2)) glucose status was tested using OGTT and HbA1c. Furthermore, the FINDRISC questionnaire and CT visceral fat (VAT) and subcutaneous fat (SAT) were examined.Results: Exactly 50.4% were found to have prediabetes and 11.1% were newly diagnosed with type 2 diabetes (T2DM) (M/F=22.2/8.8%). Subjects without T2DM had a FINDRISC score of 11±3, those with pre-DM 13±4, and subjects with de novo T2DM 15±5. The aROC of the FINDRISC for detecting T2DM was 0.76 (95% CI 0.72-0.82), with 13 as cutoff point. The FINDRISC score correlated with VAT (r=0.34, p<0.001) and VAT/SAT ratio (r=0.39, p<0.001). The aROC of the FINDRISC to detect excess VAT was 0.79 (95%CI 0.72-0.84).Conclusions: In a large group of overweight and obese subjects, 50.4% were found to have pre-DM and 11.1% were newly diagnosed with T2DM. The FINDRISC score increased with worsening of glucose tolerance status and proved to be an independent predictor of T2DM status, as did HOMA-B, HOMA-S and VAT. The FINDRISC can also function as a good tool to predict visceral obesity. [ABSTRACT FROM AUTHOR]

A recent increase in the rate of obesity as a result of insufficient physical exercise and excess food consumption has been seen in both developed and developing countries throughout the world. Additionally, the recent increased number of obese individuals with lifestyle-related diseases associated with abnormalities in glucose metabolism, dyslipidemia, and hypertension, defined as metabolic syndrome (MS), has been problematic. Although MS has been highlighted as a risk factor for ischemic heart disease and arteriosclerotic diseases, it was also recently shown to be associated with digestive system disorders, including upper gastrointestinal diseases. Unlike high body weight and high body mass index, abdominal obesity with visceral fat accumulation is implicated in the onset of various digestive system diseases because excessive visceral fat accumulation may cause an increase in intra-abdominal pressure, inducing the release of various bioactive substances, known as adipocytokines, including tumor necrosis factor-α, interleukin-6, resistin, leptin, and adiponectin. This review article focuses on upper gastrointestinal disorders and their association with MS, including obesity, visceral fat accumulation, and the major upper gastrointestinal diseases. [ABSTRACT FROM AUTHOR]

Background: It has been shown that visceral fat accumulation is associated with autonomic dysfunction, though the precise mechanism remains unclear. A recent basic study found that leptin can directly modulate autonomic function through the dorsomedial hypothalamus in relation to obesity. Here, we investigated the mutual relationships among plasma leptin, visceral fat accumulation, and cardiac autonomic dysfunction in patients with type 2 diabetes. Methods: This cross-sectional study included 100 diabetic patients, and 100 age- and gender-matched non-diabetic patients with cardiovascular risk factors. Plasma leptin and soluble leptin receptor levels, visceral fat area (VFA), and heart rate variability (HRV) were determined in addition to classical cardiovascular risk factors. Results: In the type 2 diabetic patients, VFA was significantly (p < 0.05) and inversely associated with HRV parameters (SDNN: r = -0.243; SDANN5: r = -0.238), while the plasma level of leptin, but not soluble leptin receptor, was also significantly (p < 0.05) and inversely associated with HRV parameters (SDNN: r = -0.243; SDANN5: r = -0.231). Multiple regression analysis showed that plasma leptin was significantly associated with SDNN and SDANN5 independent of other factors, including age, gender, presence of hypertension and dyslipidemia, duration of diabetes, HbA1c, and eGFR. Furthermore, the relationship of leptin with SDNN and SDANN5 (β = -0.279 and -0.254, respectively) remained significant (p < 0.05) after adjustment for VFA. In patients without diabetes, no significant associations were observed between leptin and any of the HRV parameters. Conclusions: Hyperleptinemia may be involved in cardiac autonomic dysfunction in patients with type 2 diabetes and visceral obesity. [ABSTRACT FROM AUTHOR]

Aims/Introduction Weight reduction improves glycemic control in obese men with glycated hemoglobin (HbA1c) of 5.6-6.4%, suggesting that it can prevent the development of diabetes in these patients. The aim of the present study was to quantify the amount of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation. Materials and Methods The study participants were 482 men with an estimated visceral fat area of ≥100 cm2, HbA1c of 5.6-6.4%, fasting plasma glucose ( FPG) of <126 mg/ dL or casual plasma glucose <200 mg/ dL. They were divided into two groups based on weight change at the end of the 3-year follow-up period (weight gain and weight loss groups). The weight loss group was classified into quartile subgroups (lowest group, 0 to <1.2%: second lowest group, ≥1.2 to <2.5%: second highest group, ≥2.5 to <4.3%: highest group, ≥4.3% weight loss). The development of diabetes at the end-point represented a rise in HbA1c to ≥6.5% or FPG ≥126 mg/ dL, or casual plasma glucose ≥200 mg/ dL. Results The cumulative incidence of diabetes at the end of the 3-year follow-up period was 16.2% in the weight gain group and 10.1% in the weight loss group ( P not significant). The incidence of diabetes was significantly lower in the highest weight loss group (3.1%), but not in the second highest, the second lowest and the lowest weight loss groups (9.7, 10.1 and 18.3%), compared with the weight gain group. Conclusions Minimization of the risk of diabetes in Japanese men with visceral fat accumulation requires a minimum of 4-5% weight loss in those with HbA1c of 5.6-6.4%. [ABSTRACT FROM AUTHOR]

Background Visceral fat accumulation is a major etiological factor in the progression of type 2 diabetes mellitus and atherosclerosis. We described previously visceral fat accumulation and multiple cardiovascular risk factors in a considerable number of Japanese non-obese subjects (BMI <25 kg/m2). Here, we investigated differences in systemic arteriosclerosis, serum adiponectin concentration, and eating behavior in type 2 diabetic patients with and without visceral fat accumulation. Methods The study subjects were 75 Japanese type 2 diabetes mellitus (age: 64.8 ½ 11.5 years, mean ½ SD). Visceral fat accumulation represented an estimated visceral fat area of 100 cm2 using the bioelectrical impedance analysis method. Subjects were divided into two groups; with (n = 53) and without (n = 22) visceral fat accumulation. Systemic arteriosclerosis was scored for four arteries by ultrasonography. Eating behavior was assessed based on The Guideline for Obesity questionnaire issued by the Japan Society for the Study of Obesity. Results The visceral fat accumulation (+) group showed significantly higher systemic vascular scores and significantly lower serum adiponectin levels than the visceral fat accumulation (-) group. With respect to the eating behavior questionnaire items, (+) patients showed higher values for the total score and many of the major sub-scores than (-) patients. Conclusions Type 2 diabetic patients with visceral fat accumulation showed 1) progression of systemic arteriosclerosis, 2) low serum adiponectin levels, and 3) differences in eating behavior, compared to those without visceral fat accumulation. Taken together, the findings highlight the importance of evaluating visceral fat area in type 2 diabetic patients. Furthermore, those with visceral fat accumulation might need to undergo more intensive screening for systemic arteriosclerosis and consider modifying their eating behaviors. [ABSTRACT FROM AUTHOR]

Background Non-shivering thermogenesis (NST) involves a substantial amount of energy expenditure in humans and, thus, contributes to reducing the risk for obesity. Molecular evolutionary studies have reported that SNPs in/near the uncoupling protein 3 gene (UCP3) and the regulatory associated protein of mTOR complex 1 gene (RPTOR) might influence NST and confer adaptive advantages for modern human dispersal into cold environments. In the present study, the impact of these SNPs on obesity-related traits was investigated. Methods Study subjects consisted of 2,834 Japanese adults (percentage of female: 46%, mean age: 51.5). Associations of the UCP3-55C/T and the RPTOR-26934C/T - the 2 potential genetic variations involved in cold adaptation and thermogenic mechanisms in mammals, with quantitative obesity-related traits including body mass index (BMI), waist circumference, visceral fat area (VFA), VFA adjusted for BMI, and selected blood parameters - were tested using multiple linear regression models. Sliding windowsampling analysis was applied to depict seasonal effects of the SNPs on the obesity-related phenotypes. Results UCP3-55C/T and the RPTOR-26934C/T did not show any association with obesity traits and blood chemical parameters in multiple linear regression models consisting of the whole subjects. Moreover, sliding window sampling-based association analyses involving seasonality also failed to find associations between these two SNPs and obesity-related traits. Conclusions UCP3-55C/T and the RPTOR-26934C/T may only have subtle effects on the development of obesity-related traits in the present humans. These two SNPs might be irrelevant to interindividual variations in energy metabolism and efficiency of NST. [ABSTRACT FROM AUTHOR]

A clustering of metabolic abnormalities such as dyslipidemia, hypertension, and diabetes mellitus, all of which are major risk factors for cardiovascular disease (CVD), occurs more often than by chance. Numerous epidemiological studies, as well as basic researches, have revealed that visceral fat accumulation is closely involved in this risk clustering. This morbid condition is now well recognized as the metabolic syndrome. The concept of the metabolic syndrome, i.e ., the involvement of visceral adiposity in the clustering of CVD risk factors, implies that an effective CVD risk reduction will be accomplished by an intervention to reduce visceral fat deposits. The primary strategy of the intervention is lifestyle modification, which can be put into practice in healthcare fields, without necessity of medical treatment. Now that CVD is a leading global health burden, the metabolic syndrome attracts increasing attention in the world. To take global action against the syndrome, several working groups developed its internationally unified diagnostic criteria. Most recently, the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) jointly proposed the criteria, although some cautions will be needed in their practical use. In this review, we mainly focus on the findings observed in clinical and epidemiological studies, to discuss a practical strategy of the management of the metabolic syndrome in healthcare fields. [ABSTRACT FROM AUTHOR]

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 (β = -0.22), skeletal muscle index (SMI; skeletal muscle area divided by height squared; β = 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; β = -0.08, β = -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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims/Introduction The aim of the present study was to determine whether weight reduction is associated with improvement of glycemic control in non-obese and obese subjects with or without visceral fat accumulation, whose hemoglobin A1c ( A1 C) is 5.6-6.4%. Materials and Methods A total of 798 male subjects whose A1 C levels were between 5.6% and 6.4% were divided into subgroups based on body mass index ( BMI) and/or estimated visceral fat area (e VFA), and were analyzed with respect to the relationships between 1-year changes in BMI (Δ BMI) and A1 C (Δ A1 C). Results In both the BMI ≥25 and BMI <25 groups, Δ A1 C correlated positively with Δ BMI ( BMI ≥25 ( n = 321): r = 0.236, P < 0.0001; BMI <25 ( n = 477): r = 0.095, P = 0.0387) although the r-value was very small for the latter group. In addition, for the group with e VFA ≥100 cm2 ( n = 436), Δ A1 C correlated positively with Δe VFA ( r = 0.150, P = 0.0017), but this correlation was not found for the e VFA <100 cm2 group ( n = 339, P = 0.3505). Furthermore, Δ A1 C positively correlated with Δ BMI for the groups in BMI ≥25 with e VFA >100 cm2 ( n = 293, r = 0.256, P < 0.0001) and BMI <25 with e VFA ≥100 cm2 ( n = 145, r = 0.250, P = 0.0024), but not for the groups in BMI ≥25 with e VFA <100 cm2 ( n = 28, P = 0.6401) nor BMI <25 with e VFA <100 cm2 ( n = 332, P = 0.6605). Conclusions These results suggest that the assessment of visceral fat, rather than BMI, might be more important in identifying subjects in whom lifestyle intervention aiming at weight reduction could be effective to prevent diabetes. This trial was registered with University Hospital Medical Information Network Clinical Trials Registry (no. UMIN 000002391). [ABSTRACT FROM AUTHOR]

Background: Although many Asian type 2 diabetic patients have been considered to be not obese and have low capacity of insulin secretion, the proportion of obese patients with visceral fat accumulation has increased in recent years. We found previously considerable number of Japanese non-obese subjects (body mass index (BMI) < 25 kg/m2) with visceral fat accumulation and multiple cardiovascular risk factors. The aim of the study was to investigate the difference in clinical features of type 2 diabetic patients with and without visceral fat accumulation, focusing on vascular complications and changes in BMI. Methods: We enrolled 88 Japanese hospitalized type 2 diabetic patients. Abdominal obesity represented waist circumference (WC) of ⩾85 cm for males and ⩾90 cm for females (corresponding to visceral fat area of 100 cm2). Subjects were divided into two groups; with or without abdominal obesity. Results: Hypertension, dyslipidemia and cardiovascular diseases were significantly more in the patients with abdominal obesity. The prevalence of cardiovascular disease in the non-obese patients (BMI < 25 kg/m2) with abdominal obesity were similar in obese patients (BMI ⩾25 kg/m2). The mean BMI of the patients with abdominal obesity was < 25 kg/m2 at 20 years of age, but reached maximum to more than 30 kg/m2 in the course. Furthermore, substantial portion of the type 2 diabetic patients (52% in males and 43% in females) were not obese at 20 year-old (BMI < 25 kg/m2), but developed abdominal obesity by the time of admission. Conclusion: These results emphasize the need to control multiple risk factors and prevent atherosclerotic disease in patients with abdominal obesity. The significant weight gain after 20 years of age in patients with abdominal obesity stresses the importance of lifestyle modification in younger generation, to prevent potential development of type 2 diabetes and future atherosclerotic cardiovascular disease. [ABSTRACT FROM AUTHOR]

Aim To investigate the association between Trp64 Arg polymorphism of the beta3-adrenergic receptor ( ADRB3) gene and total fat mass, abdominal fat distribution, other metabolic derangements and metabolic syndrome ( MS) in Japanese children. Methods Molecular screening of the ADRB3 gene polymorphism ( Trp64 Trp, Trp64 Arg and Arg64 Arg) was carried out in 132 children aged 6-12 years: 73 were obese (45 boys) and 59 were not obese (27 boys). Visceral fat ( VF) and subcutaneous fat ( SF) area were measured using magnetic resonance imaging, blood pressure, lipid and glucose profiles. Results The frequencies of Arg carriers ( Trp64 Arg or Arg64 Arg) were significantly higher in obese children with MS, compared to obese children without MS and nonobese children. In obese children, Arg carriers had significantly higher VF area, systolic and diastolic blood pressure, and low-density lipoprotein cholesterol and triglyceride than Arg noncarriers ( Trp64 Trp). However, there were no differences in total fat mass and SF area between the two groups. In nonobese children, none of these parameters differed significantly between Arg carriers and noncarriers. Conclusion Trp64 Arg polymorphism of the ADRB3 gene may affect VF accumulation and be associated with MS, a cluster of conditions involving aggravated lipid metabolism and higher blood pressure, in Japanese children. [ABSTRACT FROM AUTHOR]

Objective To determine whether daidzein improves insulin resistance by modifying weight gain, visceral fat accumulation, blood lipids and serum cytokines levels in ovariectomized Sprague-Dawley rats. Materials and methods Twenty-eight 12-week-old female rats were divided into three groups: the sham-operated group (SHAM) (n = 10), the ovariectomized group receiving daidzein therapy (DAID) (n = 10), and the ovariectomized control group (Control) (w = 8). The rats in the DAID group received 50 mg/kg daidzein via gavage daily. Weight and food intake were recorded every 2 weeks. All of the animals were euthanized 12 weeks after ovariectomy, after which their fasting insulin, glucose, blood lipids, estradiol, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), adiponectin and leptin levels were measured. Results After 12 weeks, the ovariectomized rats demonstrated an increase in their body weight and visceral fat; compared to the SHAM rats, the ovariectomized rats also experienced a significant increase in their serum IL-6 levels and insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR) (p<0.05). Daidzein therapy decreased weight gain, visceral fat, the HOMA-IR index and IL-6 levels that were induced by ovariectomy. Rats which had received daidzein therapy had lower levels of TNF-α, leptin and blood lipids (except for high density lipoprotein cholesterol) than the other two groups. IL-6 levels positively correlated with the HOMA-IR index in all of the rats after adjustment for body weight (r = 0.495; p = 0.016). Conclusion We conclude that daidzein can improve insulin resistance induced by ovariectomy by decreasing weight gain, visceral fat accumulation, blood lipids, TNF-α, leptin and IL-6 levels. [ABSTRACT FROM AUTHOR]

Atherosclerosis, the underlying cause of atherosclerotic cardiovascular disease, develops not only due to a single cardiovascular risk factor, but to a variety of complex factors. Body fat distribution, especially visceral fat accumulation, is a major correlate of a cluster of metabolic abnormalities and atherosclerotic cardiovascular disease in Japanese metabolic syndrome. Reduction of visceral fat through individualized lifestyle recommendations by medical personnel (health guidance 'Hoken-shido' in Japanese) contributes to changes in the number of obesity-related cardiovascular risk factors in subjects with, but not without, visceral fat accumulation. For the prevention of atherosclerotic cardiovascular disease in Japan, it might be practical to stratify subjects with multiple risk factors based on visceral fat accumulation and conduct health education ('Hoken-shido') based on conceptualization of visceral fat accumulation, from the results of the VACATION-J study, a Japanese population-based cohort study. This article discusses visceral adiposity as a target for the management of metabolic syndrome, including lessons learned from the VACATION-J study. [ABSTRACT FROM AUTHOR]

The present study was aimed at analysing body composition in children aged 13 who, while showing normal BMI, had waist circumference above the 90th percentile, indicative of visceral fat accumulation. The study showed the situation to be related both to the elevated percentage of adipose tissue in the body and to reduced percentages of fat-free body mass and water. The girls examined showed their body fat percentage to vary, within 19.5-32.7% (mean 26.9 ± 3.8%) against the reference level of 18-25%; the girls' fat-free body mass ranged within 67.3-80.5% (mean 71.3 ± 3.8%) against the reference level of 72-82%; the percentage of water in their body ranged within 50.9-60.8% (mean 55.3 2.9%) against the reference level of 57-62%. The boys examined showed their body fat percentage to vary, within 20.5-35.5% (mean 25.3 ± 6.4%) against the reference level of 12-18%; their fat-free body mass to range within 64.7-89.5% (mean 74.7 ± 6.4%) against the reference level of 82-88%; and the percentage of water in their body to vary within 48.3-66.9% (mean 55.8 ± 4.8%) against the reference level of 61-66%. As shown by the results, the normal BMI cannot be the only criterion with which to assess the nutritional status of a child, particularly at puberty. [ABSTRACT FROM AUTHOR]

Abstract: Obesity is associated with cognitive dysfunction, for which changes in the hippocampus plausibly play a pivotal role. We tested the hypothesis that an elevated level of visceral fat accumulation (VFA) correlates with hippocampus volume and insulin resistance in non-dementia patients with type 2 diabetes. Subjects included 48 non-dementia patients with type 2 diabetes, who were divided into two groups, high VFA group (mean±standard deviation: age=65±6 years, n =30) and normal VFA group (65±5 years, n =18). Hippocampus volume has been quantitated with computer-assisted analysis using a magnetic resonance imaging (MRI) voxel-based specific regional analysis system developed for the study of Alzheimer''s disease (VSRAD), which yields a Z-score as the end point for assessment of hippocampal volume. The Z-score was higher in the high VFA group than in the normal VFA group (p <0.0001). The fasting plasma glucose (p <0.05) and insulin concentrations (p <0.0001) and the homeostasis model assessment (HOMA) index (p <0.0001) were higher in the high VFA group than in the normal VFA group. Multiple regression analysis showed that VFA levels were independently predicted by Z-score and HOMA index. Our results indicate that the elevated level of VFA in Japanese non-dementia patients with type 2 diabetes is characterized by increased hippocampus volume and insulin resistance, and that the Z-score and HOMA index are independent predictors of VFA. [Copyright &y& Elsevier]

Abstract: The association of bone with the metabolic syndrome and its features, visceral fat accumulation or insulin resistance, remains unclear. We determined visceral and subcutaneous fat areas (V and S) by computed tomography on 187 men (28–83 years) and 125 postmenopausal women (46–82 years) with type 2 diabetes. Men whose V was 100 cm2 or more had significantly lower urinary N-terminal cross-linked telopeptide of type-I collagen (p =0.005), higher femoral neck bone mineral density (FN-BMD) (p =0.004), and lower prevalence of vertebral fractures (VFs) (p =0.04) than controls. Fat mass, V, S, and lean body mass positively correlated with FN-BMD in men and with lumbar (L) and FN-BMD in women. When adjusted for weight, these correlations became negative. Urinary C-peptide positively correlated with FN-BMD in both genders. Multivariate logistic regression analysis adjusted for age, height, weight, L-BMD, duration of diabetes, and diabetes therapies identified V in men and urinary C-peptide in women as factors inversely associated with the presence of VFs [odds ratio (OR)=0.61 per SD increase, p =0.04, and OR=0.32, p =0.01, respectively]. These findings suggest that, of the components of the metabolic syndrome, body fat in gravity and hyperinsulinemia could increase FN-BMD in diabetic subjects. Visceral fat in men and hyperinsulinemia in women may protect against VFs independent of weight, L-BMD, diabetes duration, or therapies. [Copyright &y& Elsevier]

Background The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. The elevated visceral fat accumulation (VFA) has been reported to be closely related to the development of atherosclerosis. This preliminary study was therefore designed to test the hypothesis that the presence of WML correlates with VFA and insulin resistance in type 2 diabetic patients not receiving insulin treatment. Material and methods Based on brain magnetic resonance imaging (MRI), 95 type 2 diabetic patients were divided into two groups: WML-positive group (aged 59 ± 7 years, mean ± SD n = 37) and WML-negative group (aged 58 ± 5, years, n = 58). The level of blood glucose was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin, homeostasis model assessment (HOMA) index, and haemoglobin A1c. The fat distribution was evaluated by measuring the visceral fat accumulation by abdominal computerized tomography at the umbilical level. Results The body mass index was higher in the WML-positive group than in the WML-negative group ( P < 0·005). Plasma levels of triglycerides were higher while high-density lipoprotein cholesterol was lower in the WML-positive group than in the WML-negative group ( P < 0·05 and P < 0·01, respectively). FPG ( P < 0·01), insulin concentrations ( P < 0·0001), HOMA index ( P < 0·0001) and VFA (<0·0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the high VFA and insulin resistance ( P < 0·001, P < 0·0001, respectively). Conclusions The results of this preliminary study indicate that the presence of WML was associated with the high VFA and insulin resistance in Japanese patients with type 2 diabetes mellitus. Further larger cohort studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Association between metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) was verified and significance of liver function tests, especially alanine aminotransferase/aspartate aminotransferase ratio (ALT/AST) to evaluate the statuses of MetS and/or visceral fat accumulation was examined. Materials and Methods: After excluding subjects with liver diseases other than NAFLD, 1643 male and 1764 female Japanese were cross-sectionally examined. The diagnosis of MetS was done by its clinical criteria for Japanese with some modifications. Results: Levels of AST, ALT, gamma glutamyl transpeptidase and ALT/AST were significantly higher in subjects with MS than in those without it. Stepwise regression analyses indicated that AST, ALT, and ALT/AST in male and ALT/AST in female were significantly associated with waist circumference (WC), a marker of visceral fat accumulation. Among these associations, the association between WC and ALT/AST was always significant even when subjects with normal level of ALT of WC were selectively examined. Conclusions: NAFLD can be considered as one of morbid conditions of MetS, i.e. visceral fat accumulation. Among liver function test items, ALT/AST could be a powerful index reflecting their progression even in their pre-diagnosis/silent phases. [Copyright &y& Elsevier]

We tested the hypothesis that increased abdominal visceral accumulation (VFA) is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients not receiving insulin treatment. The fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. The study group consisted of 24 type 2 diabetic patients with high VFA (≥100 cm2, age 60 ± 8 years, high VFA group). The control group consisted of 19 age-matched type 2 diabetic patients with normal VFA (<100 cm2, age 60 ± 7 years, normal VFA group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations, and cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy. Early and delayed 123I-MIBG myocardial uptake values were lower ( p < 0.005 and p < 0.0001, respectively) and the percent washout rate of 123I-MIBG was higher ( p < 0.0005) in the high VFA group than in the normal VFA group. The fasting plasma insulin concentrations ( p < 0.005) and the homeostasis model assessment (HOMA) index values ( p < 0.0005) were higher in the high VFA group than in normal VFA group. Multiple regression analysis revealed that the level of VFA was independently predicted by the HOMA index values and the myocardial uptake of 123I-MIBG during the delayed phase. Our results demonstrate that the level of VFA is associated with depressed cardiovascular autonomic function and insulin resistance in patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Abstract: Using preadipocyte implantation methods, we recently demonstrated that adipocytes in the visceral area change their function, as the expression of tumor necrosis factor-α (TNF-α) increases, thereby causing insulin resistance. In order to clarify the mechanism for changes in the function of adipocytes in visceral area, we examined the mRNA expression profiles in visceral fat tissue specimens. Four weeks after cell implantation, we performed a microarray analysis using the RNA of fat tissue specimens implanted either with 3T3-L1 cells or PBS alone. Sixty-three genes were thus isolated and the expression of matrix metalloproteinase-3 (MMP-3) mRNA was found to dramatically increase in the fat tissue specimens. The neutralization of MMP-3 protein inhibited adipogenesis and the free fatty acid-induced TNF-α secretion in 3T3-L1 adipocytes. These results suggest a potential role of MMP-3, which promotes the TNF-α secretion, thus contributing to the disturbance of the functions in the adipocytes which accumulate in the visceral area. [Copyright &y& Elsevier]

To elucidate the role of visceral fat accumulation in the metabolic syndrome, differences in the pathology of the metabolic syndrome with or without visceral fat accumulation were investigated. A total of 472 prediabetic Japanese men (mean age, 47.5±7.2 yr) with impaired fasting glycemia (IFG) levels of 110–125 mg/dL were eligible for participation in the study. The study subjects were divided into the following four groups, and intergroup comparisons were made: group I without visceral fat area [VFA]≥100 cm2 but presenting with fewer than two other risk factors (i.e., TG≥150 mg/dL, HDL-C<40 mg/dL, BP≥130/≥85 mmHg, or FPG≥110 mg/dL) ( n=231); group II without VFA of ≥100 cm2 but presenting with three or more other risk factors ( n=57); group III with VFA of ≥100 cm2 accompanied by FPG≥110 mg/dL alone ( n=27); and group IV with VFA≥100 cm2 and two or more other risk factors ( n=157). The prevalence of patients who had three or more risk factors with or without VFA≥100 cm2 was 45.3% (214 out of 472 patients), while that of those with VFA≥100 cm2 who had two or more other risk factors was 33% (157 out of 472 patients). Group II had significantly higher VFA values than group I ( p<0.05), and group IV had significantly higher VFA values than group II ( p<0.001). While no significant differences in HOMA-R values were seen between groups I and II, these values were significantly higher in group IV compared to groups I and II ( p<0.001 and p<0.05, respectively). Furthermore, group IV showed significantly higher 2-h insulin levels after glucose loading compared to group I ( p<0.001). While no significant differences were seen between groups II and IV, insulin levels tended to be higher in group IV. Adiponectin levels showed an incremental fall in VFA from group I through groups II and III to group IV. Groups III and IV showed significantly lower adiponectin levels compared to group I ( p<0.05, p<0.001, respectively); and group IV showed significantly lower adiponectin levels than group II ( p<0.05). A logistic regression analysis using VFA, TG and HDL-C, and BP as explanatory variables showed that the relative risk for high HOMA-R values were 2.65 ( p<0.001) for patients with VFA ≥100 cm2; 1.64 ( p<0.05) for those with TG≥150 mg/dL and HDL<40 mg/dL; and 1.79 ( p<0.01) for those with BP≥130/≥85 mmHg. These findings demonstrate that the degree of insulin resistance and the risk of arteriosclerosis vary depending on whether or not the metabolic syndrome accompanied by a clustering of risk factors has visceral fat accumulation as an underlying pathology, strongly suggesting a crucial role for visceral fat accumulation in the metabolic syndrome. [ABSTRACT FROM AUTHOR]