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Visceral Adiposity and Glucoregulatory Peptides are Associated with Susceptibility to Type 2 Diabetes: The TOFI_Asia Study.
Sequeira, IR, Yip, W, Lu, L, Jiang, Y, Murphy, R, Plank, L, Zhang, S, Liu, H, Chuang, CL, Vazhoor-Amarsingh, G, et al
Obesity (Silver Spring, Md.). 2020;(12):2368-2378
Abstract
OBJECTIVE Ethnic differences in fat deposition contribute to type 2 diabetes (T2D). Identification of biomarkers that underpin dysglycemia are needed for better-targeted prevention and treatment. METHODS The cross-sectional thin-on-the-outside-fat-on-the-inside (TOFI)_Asia study investigated adipose depots and clinical biomarkers as predictors of fasting plasma glucose (FPG) and insulin resistance (IR; assessed using the updated homeostatic model assessment of IR) in lean and overweight normo- and dysglycemic Chinese (n = 199) and Caucasian (n = 158) individuals. Multivariate least-angle regression models were used to identify predictors of FPG and IR. RESULTS At similar age and BMI, Chinese individuals had lower body weight but had a greater percentage of total abdominal adipose tissue and a greater percentage of total visceral adipose tissue (VAT) (all P < 0.005). In Chinese individuals, FPG, hemoglobin A1c , fasting insulin, and triglycerides were higher, whereas HDL cholesterol and total and high-molecular-weight adiponectin levels were lower (all P < 0.0001). Raised liver enzyme and peptide concentrations (P < 0.02) were consistent with increased T2D risk. Lean Chinese women (<25 kg/m2 ) had greater total abdominal adipose tissue (kilograms) and VAT (kilograms) than Caucasian women, exhibiting the TOFI profile, with raised FPG (P < 0.001) and IR (P = 0.01). Risk factors for elevated FPG specific to Chinese individuals included male gender, VAT, and triglycerides (R2 = 0.33), and risk factors for IR specific to Chinese individuals included amylin, C-peptide, and glucagon (R2 = 0.49). VAT, amylin, and C-peptide were predictors in Caucasian individuals. CONCLUSIONS VAT contributed to dysglycemia in both ethnicities, particularly in Chinese individuals characterized by the TOFI phenotype, as did the glucoregulatory peptides amylin and C-peptide, providing targets for T2D prevention.
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Increased Visceral Adipose Tissue Without Weight Retention at 59 Weeks Postpartum.
Janumala, I, Toro-Ramos, T, Widen, E, Rosenn, B, Crane, J, Horowitz, M, Lin, S, Gidwani, S, Paley, C, Thornton, JC, et al
Obesity (Silver Spring, Md.). 2020;(3):552-562
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OBJECTIVE This study aimed to determine whether controlling maternal gestational weight gain (GWG) influences adipose tissue distribution at 1 year postpartum. METHODS Women with overweight or obesity (n = 210, BMI ≥ 25 or ≥ 30) were randomized to a lifestyle intervention (LI) designed to control GWG or to usual obstetrical care (UC). Measures included anthropometry, whole-body magnetic resonance imaging for visceral (VAT), intermuscular, and subcutaneous adipose tissue, and cardiometabolic risk factors in pregnancy (15 and 35 weeks) and after delivery (15 and 59 weeks). RESULTS Baseline (15 weeks) characteristics were similar (mean [SD]: age, 33.8 [4.3] years; weight, 81.9 [13.7] kg; BMI, 30.4 [4.5]; gestational age at randomization, 14.9 [0.8] weeks). LI had less GWG (1.79 kg; P = 0.003) and subcutaneous adipose tissue gain at 35 weeks gestation (P < 0.01). UC postpartum weight (2.92 kg) was higher at 15 weeks but not different from baseline or LI at 59 weeks postpartum. Postpartum VAT increased from baseline in LI by 0.23 kg at 15 weeks and 0.55 kg at 59 weeks; in UC, it increased by 0.34 kg at 15 and 59 weeks. Intermuscular adipose tissue remained elevated in LI (0.22 kg) at 59 weeks. VAT was associated with several cardiometabolic risk factors at 59 weeks. CONCLUSIONS Despite no weight retention at 59 weeks postpartum, women had increased VAT by ~30%. Postpartum modifiable behaviors are warranted to lower the risk of VAT retention.
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Free-amino acid metabolic profiling of visceral adipose tissue from obese subjects.
Piro, MC, Tesauro, M, Lena, AM, Gentileschi, P, Sica, G, Rodia, G, Annicchiarico-Petruzzelli, M, Rovella, V, Cardillo, C, Melino, G, et al
Amino acids. 2020;(8):1125-1137
Abstract
Interest in adipose tissue pathophysiology and biochemistry have expanded considerably in the past two decades due to the ever increasing and alarming rates of global obesity and its critical outcome defined as metabolic syndrome (MS). This obesity-linked systemic dysfunction generates high risk factors of developing perilous diseases like type 2 diabetes, cardiovascular disease or cancer. Amino acids could play a crucial role in the pathophysiology of the MS onset. Focus of this study was to fully characterize amino acids metabolome modulations in visceral adipose tissues (VAT) from three adult cohorts: (i) obese patients (BMI 43-48) with metabolic syndrome (PO), (ii) obese subjects metabolically well (O), and (iii) non obese individuals (H). 128 metabolites identified as 20 protein amino acids, 85 related compounds and 13 dipeptides were measured by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) and gas chromatography-/mass spectrometry GC/MS, in visceral fat samples from a total of 53 patients. Our analysis indicates a probable enhanced BCAA (leucine, isoleucine, valine) degradation in both VAT from O and PO subjects, while levels of their oxidation products are increased. Also PO and O VAT samples were characterized by: elevated levels of kynurenine, a catabolic product of tryptophan and precursor of diabetogenic substances, a significant increase of cysteine sulfinic acid levels, a decrease of 1-methylhistidine, and an up regulating trend of 3-methylhistidine levels. We hope this profiling can aid in novel clinical strategies development against the progression from obesity to metabolic syndrome.
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Vertebral Bone Marrow Fat Is independently Associated to VAT but Not to SAT: KORA FF4-Whole-Body MR Imaging in a Population-Based Cohort.
Hasic, D, Lorbeer, R, Bertheau, RC, Machann, J, Rospleszcz, S, Nattenmüller, J, Rathmann, W, Peters, A, Bamberg, F, Schlett, CL
Nutrients. 2020;(5)
Abstract
The objective of the current study was to assess the relationship of bone marrow adipose tissue (BMAT) content to abdominal fat depots, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), as well as cardiovascular risk factors (CVRF) beyond physical activity in a population-based cohort study undergoing whole-body magnetic resonance (MR) imaging. Subjects of the Cooperative Health Research in the Augsburg Region (KORA) FF4 study without known cardiovascular disease underwent fat fraction quantification in vertebrae (BMATL1/L2) via a 2-point T1-weighted volumetric interpolated breath-hold examination (VIBE) Dixon sequence. The same MR sequence was applied to quantify VAT and SAT volume. Subjects' characteristics, including physical activity, were determined through standardized exams and self-assessment questionnaires. Univariate and multivariate linear regression were applied. In the cohort of 378 subjects (56 ± 9.1years; 42.1% female), BMATL1/L2 was 54.3 ± 10.1%, VAT was 4.54 ± 2.71 L, and SAT was 8.10 ± 3.68 L. VAT differed significantly across BMATL1/L2 tertiles (3.60 ± 2.76 vs. 4.92 ± 2.66 vs. 5.11 ± 2.48; p < 0.001), there was no significant differences for SAT (p = 0.39). In the fully adjusted model, VAT remained positively associated with BMATL1/L2 (β = 0.53, p = 0.03). Furthermore, BMATL1/L2 was associated with age (β = 5.40 per 10-years, p < 0.001), hemoglobin A1c (HbA1c; β = 1.55 per 1%, p = 0.04), lipids (β = 0.20 per 10 mg/dL triglycerides; β = 0.40 per 10 mg/dL low-density lipoprotein (LDL); β =-3.21 lipid-lowering medication; all p < 0.05), and less physical activity (β = 3.7 "no or nearly no exercise" as compared to "≥2 h per week, regularly", p = 0.003); gender was not significantly different (p = 0.57). In the population-based cohort, VAT but not SAT were associated with higher BMATL1/L2 independently of physical activity and other cardiovascular risk factors. Further, BMATL1/L2 increased with older age, less physical activity, higher HbA1c, and increased lipids but decreased with lipid-lowering medication.
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Intra-Abdominal Fat and High Density Lipoprotein Cholesterol Are Associated in a Non-Linear Pattern in Japanese-Americans.
Song, SO, Hwang, YC, Kahn, SE, Leonetti, DL, Fujimoto, WY, Boyko, EJ
Diabetes & metabolism journal. 2020;(2):277-285
Abstract
BACKGROUND We describe the association between high density lipoprotein cholesterol (HDL-C) concentration and computed tomography (CT)-measured fat depots. METHODS We examined the cross-sectional associations between HDL-C concentration and intra-abdominal (IAF), abdominal subcutaneous (SCF), and thigh fat (TF) areas in 641 Japanese-American men and women. IAF, SCF, and TF were measured by CT at the level of the umbilicus and mid-thigh. The associations between fat area measurements and HDL-C were examined using multivariate linear regression analysis adjusting for age, sex, diabetes family history, homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Non-linearity was assessed using fractional polynomials. RESULTS Mean±standard deviation of HDL-C concentration and IAF in men and women were 1.30±0.34 mg/dL, 105±55.3 cm², and 1.67±0.43 mg/dL, 74.4±46.6 cm² and differed significantly by gender for both comparisons (P<0.001). In univariate analysis, HDL-C concentration was significantly associated with CT-measured fat depots. In multivariate analysis, IAF was significantly and non-linearly associated with HDL-C concentration adjusted for age, sex, BMI, HOMA-IR, SCF, and TF (IAF: β=-0.1012, P<0.001; IAF²: β=0.0008, P<0.001). SCF was also negatively and linearly associated with HDL-C (β=-0.4919, P=0.001). CONCLUSION HDL-C does not linearly decline with increasing IAF in Japanese-Americans. A more complex pattern better fits this association.
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Chia (Salvia hispanica)-supplemented diet ameliorates non-alcoholic fatty liver disease and its metabolic abnormalities in humans.
Medina-Urrutia, A, Lopez-Uribe, AR, El Hafidi, M, González-Salazar, MDC, Posadas-Sánchez, R, Jorge-Galarza, E, Del Valle-Mondragón, L, Juárez-Rojas, JG
Lipids in health and disease. 2020;(1):96
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a public health problem lacking an approved pharmacological treatment. Omega-3 fatty acids have shown to reverse NAFLD. Chia is a seed rich in α-linolenic acid (ALA), antioxidants, and fiber; therefore, it could be useful to treat NAFLD. METHODS In a single arm experimental design study, the effect of 25 g/day of milled chia was assessed in 25 patients with NAFLD. After two weeks of dietary stabilization (basal condition) and eight weeks of a chia-supplemented isocaloric diet, liver:spleen attenuation index and visceral abdominal fat (VAF) were measured by computed tomography. Lipids, lipoproteins, free fatty acids (FFA), and ALA plasma concentrations were also determined. RESULTS Dietary chia supplementation induced an increase in plasma ALA concentration (75%) and dietary fiber (55%) consumption. After chia supplementation, VAF (9%), body weight (1.4%), total cholesterol (2.5%), non-high density lipoprotein cholesterol (3.2%), and circulating FFA (8%) decreased. Furthermore, NAFLD regressed in 52% of the treated patients (P < 0.05 for all). CONCLUSIONS The results of the present study show that 25 g/day of milled chia ameliorates NAFLD. Chia is an accessible vegetal source of omega-3 fatty acids, antioxidants, and fiber, which could have the potential to prevent metabolic abnormalities in NAFLD patients. Considering that there is no pharmacological treatment approved for NAFLD, the findings of the present study suggest that a chia-supplemented diet could be an innovative alternative to control this disease. RETROSPECTIVELY REGISTERED https://clinicaltrials.gov/show/NCT03942822.
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The reduction impact of monoglucosyl rutin on abdominal visceral fat: A randomized, placebo-controlled, double-blind, parallel-group.
Hashizume, Y, Tandia, M
Journal of food science. 2020;(10):3577-3589
Abstract
Water soluble α-glycosylated rutin (4G-α-D-glucopyranosyl rutin, monoglucosyl rutin, MR) was used in this study to evaluate its ability to reduce abdominal visceral fat (AVF). We conducted a study examining 66 healthy Japanese men and women with a body mass index of ≥23 and <30 kg/m2 for 8 weeks. The subjects were randomly assigned to groups via computer random numbers as follows: MR200 group (MR 200 mg/day), MR400 group (MR 400mg/day), or placebo group. The primary outcome was change in the AVF area after 8 weeks of intervention. The secondary outcomes were effects of MR on total fat and subcutaneous fat of umbilical area, lipid-related markers, and subjective symptoms. The per-protocol set analysis involved 18 subjects in the placebo group (7 males and 11 females), 20 subjects in the MR200 group (8 males and 12 females), and 20 subjects in the MR400 group (8 males and 12 females). AVF area in both the MR200 and MR400 groups was reduced at week 8, with changes from the baseline (week 0) significantly higher than the placebo group. Additionally, the MR400 group reported improved subjective symptoms concerning being "worried about abdominal fat" at week 4 compared with the placebo group. These results indicate that the consumption of MR (200 and 400 mg/day) for 8 weeks reduced AVF. PRACTICAL APPLICATION Monoglucosyl rutin, an enzymatically modified form of rutin, is a highly stable and water-soluble flavonoid widely used in food and beverages to prevent oxidation. The present clinical study demonstrated that it may improve overall health by reducing abdominal visceral fat.
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Added sugar intake is associated with pericardial adipose tissue volume.
Yi, SY, Steffen, LM, Terry, JG, R Jacobs, D, Duprez, D, Steffen, BT, Zhou, X, Shikany, JM, Harnack, L, J Carr, J
European journal of preventive cardiology. 2020;(18):2016-2023
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AIM: The purpose of this study was to determine the relationships of pericardial adipose tissue and visceral adipose tissue volume with added sugar and sugar-sweetened beverage intakes. We hypothesized that both added sugar and sugar-sweetened beverages were positively associated with pericardial adipose tissue and visceral adipose tissue volumes in black and white men and women enrolled in the prospective Coronary Artery Risk Development in Young Adults study. METHODS AND RESULTS Dietary intake was assessed by diet history at baseline, year 7 and year 20 examinations in 3070 participants aged 18-30 and generally healthy at baseline. After 25 years follow-up, participants underwent a computed tomography scan of chest and abdomen; the computed tomography scans were read, and pericardial adipose tissue, visceral adipose tissue, and subcutaneous adipose tissue volumes were calculated. Quintiles were created for the average of baseline, year 7 and year 20 added sugar and for the average of sugar-sweetened beverages. General linear regression analysis evaluated the associations of pericardial adipose tissue and visceral adipose tissue volumes across quintiles of added sugar and across quintiles of sugar-sweetened beverage intakes adjusted for potential confounding factors. In a multivariable model, pericardial adipose tissue volume was higher across increasing quintiles of added sugar and sugar-sweetened beverage intakes (ptrend = 0.001 and ptrend < 0.001, respectively). A similar relation was observed for visceral adipose tissue (ptrend < 0.001 for both added sugar and sugar-sweetened beverages). CONCLUSIONS Long-term intakes of added sugar and sugar-sweetened beverages were associated with higher pericardial adipose tissue, visceral adipose tissue, and subcutaneous adipose tissue volumes. Because these ectopic fat depots are associated with greater risk of disease incidence, these findings support limiting intakes of added sugar and sugar-sweetened beverages.
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Efficacy and Safety of Lipase Inhibitor Orlistat in Japanese with Excessive Visceral Fat Accumulation: 24-Week, Double-Blind, Randomized, Placebo-Controlled Study.
Shirai, K, Fujita, T, Tanaka, M, Fujii, Y, Shimomasuda, M, Sakai, S, Samukawa, Y
Advances in therapy. 2019;(1):86-100
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INTRODUCTION Orlistat is an inhibitor of pancreatic lipase and is used as an anti-obesity drug in many countries. However, there are no data available regarding the effects of orlistat on visceral fat accumulation in Japanese subjects. Therefore, this comparative, placebo-controlled, double-blind, randomized study aimed to evaluate the efficacy and safety of orlistat in Japanese participants with excessive visceral fat accumulation and without dyslipidemia, diabetes mellitus, and hypertension ("metabolic diseases"). METHODS The study population included Japanese participants with excessive visceral fat accumulation (waist circumference ≥ 85 cm in males and ≥ 90 cm in females, which corresponds to a visceral fat area of 100 cm2) and without metabolic diseases. Following a 12-week observation term, participants were randomized to the orlistat 60 mg group (n = 100) or placebo group (n = 100). Both drugs were administered orally three times daily for 24 weeks. Participants were also counseled to improve their diet and to maintain exercise throughout the study. Visceral fat area, subcutaneous fat area, waist circumference, body weight, body mass index, adverse reactions, laboratory tests, and blood pressure were regularly assessed. RESULTS Visceral fat area, waist circumference, and body weight were significantly reduced in the orlistat group (mean ± standard error, - 13.50 ± 1.52%, - 2.51 ± 0.25%, and - 2.79 ± 0.30%, respectively) compared to the placebo group (- 5.45 ± 1.50%, - 1.55 ± 0.26%, and - 1.22 ± 0.28%, respectively) at the last assessment. The main adverse reactions were defecation-related symptoms including oily spotting and flatus with discharge, resulting from the pharmacological effects of orlistat. Most adverse reactions were mild, and none were serious or severe. CONCLUSION Orlistat administration reduced visceral fat area, waist circumference, and body weight in Japanese participants with excessive visceral fat and without metabolic diseases. In addition, safety was confirmed with a tolerable profile. Orlistat may be useful to reduce excessive visceral fat accumulation when used in combination with diet and exercise. TRIAL REGISTRATION Japan Pharmaceutical Information Center identifier, JapicCTI-184005. FUNDING Taisho Pharmaceutical Co., Ltd.
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Intra-Abdominal Adipose Tissue Quantification by Alternative Versus Reference Methods: A Systematic Review and Meta-Analysis.
Murphy, J, Bacon, SL, Morais, JA, Tsoukas, MA, Santosa, S
Obesity (Silver Spring, Md.). 2019;(7):1115-1122
Abstract
OBJECTIVE This meta-analysis aimed to assess the agreement between intra-abdominal adipose tissue (IAAT) quantified by alternative methods and the reference standards, computed tomography (CT) and magnetic resonance imaging (MRI). METHODS MEDLINE and EMBASE electronic databases were systematically searched to identify studies that quantified IAAT thickness, area, or volume by a comparator method and CT or MRI. Using an inverse variance weighted approach (random-effects model), the mean differences and 95% limits of agreement (LoA) were pooled between methods. RESULTS The meta-analysis included 24 studies using four comparator methods. The pooled mean differences were -0.3 cm (95% LoA: -3.4 to 3.2 cm; P = 0.400) for ultrasound and -11.6 cm2 (95% LoA: -43.1 to 19.9 cm2 ; P = 0.004) for bioelectrical impedance analysis. Dual-energy x-ray absorptiometry (DXA) quantified both IAAT area and volume with mean differences of 8.1 cm2 (95% LoA: -98.9 to 115.1 cm2 ; P = 0.061) and 10 cm3 (95% LoA: -280 to 300 cm3 ; P = 0.808), respectively. CONCLUSIONS Ultrasound and DXA measure IAAT with minimal bias from CT or MRI, while bioelectrical impedance analysis systematically underestimates IAAT. However, with the exception of DXA for IAAT volume, the wide LoA caution against clinical or research use of the comparator methods and emphasize the need to optimize alternatives to the reference standards.