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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.
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The MC4R genetic variants are associated with lower visceral fat accumulation and higher postprandial relative increase in carbohydrate utilization in humans.
Adamska-Patruno, E, Goscik, J, Czajkowski, P, Maliszewska, K, Ciborowski, M, Golonko, A, Wawrusiewicz-Kurylonek, N, Citko, A, Waszczeniuk, M, Kretowski, A, et al
European journal of nutrition. 2019;(7):2929-2941
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PURPOSE The interactions between lifestyle and genetic factors play an important role in obesity development. Mutations in melanocortin-4-receptor (MC4R) gene are one of the most common cause of monogenic obesity, however, the functional effects of polymorphic variants near MC4R gene in general populations remain uncertain. The aim of our study was to analyze whether the common single nucleotide polymorphisms (SNPs) of MC4R gene influence the food preferences, physical activity, body fat content and distribution, as well as fasting and postprandial energy expenditure and substrates utilization. METHODS We genotyped previously identified MC4R SNPs: rs17782313, rs633265, rs1350341, rs12970134 in 927 subjects, who underwent anthropometric, total body fat content, visceral (VAT) and subcutaneous adipose tissue (SAT) measurements, and daily physical activity and dietary intake analysis. In randomly selected 47 subjects the energy expenditure, carbohydrate and lipid utilizations were evaluated in fasting state and after high-carbohydrate and control meals intake. RESULTS We found the significant associations between studied SNPs of MC4R gene and VAT and VAT/SAT ratio. Moreover, the GG genotype carriers of rs1350341, who had the lowest VAT accumulation (p = 0.012), presented higher relative increase in postprandial carbohydrate utilization (p = 0.013, p = 0.024). CONCLUSIONS We have observed that common SNPs of the MC4R gene influence the body fat content and distribution, as well as relative increase in postprandial carbohydrate utilization. We believe that our study may help to understand better the impact of MC4R gene on obesity development, and to help to provide personalized prevention/treatment strategies to fight against obesity and its metabolic consequences.
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Effects of exercise intervention on visceral fat in obese children and adolescents.
Jung, HC, Jeon, S, Lee, NH, Kim, K, Kang, M, Lee, S
The Journal of sports medicine and physical fitness. 2019;(6):1045-1057
Abstract
INTRODUCTION This meta-analysis study was aimed to assess the effects of exercise intervention on visceral fat in obese children and adolescents. EVIDENCE ACQUISITION Electronic database searches were performed in Academic Search Complete, CINAHL, Healthsource, MEDLINE, and SportDiscus, and from the earliest record to November 2017. Keywords included "exercise or training," "visceral fat," and "child or adolescent or youth." The inclusion criteria for eligible studies were as follows: 1) subjects were obese at baseline; 2) aged 6-19 years; 3) visceral fat was reported at baseline and after an intervention; and 4) studies were published in peer-reviewed journals written in English. EVIDENCE SYNTHESIS A total of 207 studies were observed at the initial search and 73 effect sizes (ESs) were derived from the 34 selected studies. The overall exercise intervention effect was large (Cohen's d [ES]=-1.003, 95% CI=-1.114, -0.892). Moderator analyses results showed that gender (Qb=8.23, df=2, P=0.016), exercise type (Qb=10.68, df=2, P=0.005), and intervention length (Qb=24.71, df=2, P<0.001) influenced the overall ES. CONCLUSIONS The group of both boys and girls (ES=-0.95) who participated combined exercise program (Aerobic + Resistance training; ES=-1.17) for 12 months (ES=-1.24) appeared to be the most effective exercise strategy for reducing visceral fat in obese youth.
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Comparing the effects of ipragliflozin versus metformin on visceral fat reduction and metabolic dysfunction in Japanese patients with type 2 diabetes treated with sitagliptin: A prospective, multicentre, open-label, blinded-endpoint, randomized controlled study (PRIME-V study).
Koshizaka, M, Ishikawa, K, Ishibashi, R, Maezawa, Y, Sakamoto, K, Uchida, D, Nakamura, S, Yamaga, M, Yokoh, H, Kobayashi, A, et al
Diabetes, obesity & metabolism. 2019;(8):1990-1995
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A prospective, multicentre, open-label, blinded-endpoint, randomized controlled study was conducted to evaluate the efficacy of treatment with ipragliflozin (sodium-dependent glucose transporter-2 inhibitor) versus metformin for visceral fat reduction and glycaemic control among Japanese patients with type 2 diabetes treated with sitagliptin, HbA1c levels of 7%-10%, and body mass index (BMI) ≥ 22 kg/m2 . Patients were randomly assigned (1:1) to receive ipragliflozin 50 mg or metformin 1000-1500 mg daily. The primary outcome was change in visceral fat area as measured by computed tomography after 24 weeks of therapy. The secondary outcomes were effects on glucose metabolism and lipid metabolism. Mean percentage reduction in visceral fat area was significantly greater in the ipragliflozin group than in the metformin group (-12.06% vs. -3.65%, P = 0.040). Ipragliflozin also significantly reduced BMI, subcutaneous fat area, waist circumference, fasting insulin, and homeostatic model assessment (HOMA)-resistance, and increased HDL-cholesterol levels. Metformin significantly reduced HbA1c and LDL-cholesterol levels and increased HOMA-beta. There were no severe adverse events. The use of ipragliflozin or metformin in combination with dipeptidyl peptidase-4 inhibitors, widely used in Japan, may have beneficial effects in ameliorating multiple cardiovascular risk factors.
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Effects of Interval Training on Visceral Adipose Tissue in Centrally Obese 70-Year-Old Individuals: A Randomized Controlled Trial.
Ballin, M, Lundberg, E, Sörlén, N, Nordström, P, Hult, A, Nordström, A
Journal of the American Geriatrics Society. 2019;(8):1625-1631
Abstract
OBJECTIVE To investigate the effects of 10 weeks of progressive vigorous-intensity interval training as a single intervention on body composition among 70-year-old individuals with central obesity. DESIGN Randomized controlled trial (ClinicalTrials.gov registration No. NCT03450655). SETTING Community-dwelling 70-year-old men and women living in the Umeå municipality in Sweden. PARTICIPANTS Seventy-seven 70-year-old men and women with central obesity (greater than 1 kg visceral adipose tissue [VAT] for women and greater than 2 kg VAT for men). INTERVENTION Participants allocated to the intervention group were offered a 10-week progressive concurrent exercise program performed three times per week. All participants in both groups had received tailored lifestyle recommendations focused on diet and physical activity at one occasion within 12 months prior to trial initiation. MEASUREMENTS The primary outcome was changes in VAT, and secondary outcomes included changes in total fat mass (FM), total lean body mass (LBM), and body mass index. RESULTS Comparing the groups, there were no significant differences in decrease of VAT mass (P = .10), although the intervention group significantly decreased FM by 716 g (P = .01) and gained LBM by 508 g (P = .03), compared to the control group. Furthermore, the effects of the training were significantly greater in the male subcohort (P < .05 for interaction), with positive effects also on VAT and FM, where men in the intervention group decreased VAT by 175 g (P < .05) and FM by 1364 g (P = .004), compared to the male controls. CONCLUSIONS The present trial demonstrates that 10 weeks of progressive vigorous interval training is sufficient to significantly decrease FM in older adults with central obesity, with positive effects also on LBM. J Am Geriatr Soc 67:1625-1631, 2019.
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Effect of Daily Ingestion of Quercetin-Rich Onion Powder for 12 Weeks on Visceral Fat: A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study.
Nishimura, M, Muro, T, Kobori, M, Nishihira, J
Nutrients. 2019;(1)
Abstract
Quercetin, which is frequently found in vegetables such as onion, is widely found to have biological activities such as visceral fat reduction. Therefore, we performed this randomised double-blind placebo-controlled parallel-group study and analysed the effects of daily intake of quercetin-rich onion on visceral fat for 12 weeks. Seventy healthy Japanese subjects whose body mass index (BMI) was ≥23 and <30 were recruited and randomly assigned to either the quercetin-rich onion group or placebo group. The subjects ingested 9 g of onion powder per day for 12 weeks. We conducted medical interviews, hematological and biological tests; measured body composition and vital signs; and analysed the Food Frequency Questionnaire weeks 0, 4, 8, and 12. Abdominal fat area was measured using computed tomography scanning at weeks 0 and 12. No significant differences in visceral fat area (VFA) were observed between the two groups. However, in subjects whose high-density lipoprotein cholesterol was lower, VFA was significantly lower in the quercetin-rich onion group. In addition, alanine aminotransferase was significantly lower in the quercetin-rich onion group than in the placebo group. Thus, the results suggest that quercetin-rich onion may be beneficial for preventing obesity and improving liver function.
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Visceral adiposity index outperforms common anthropometric indices in predicting 10-year diabetes risk: Results from the ATTICA study.
Koloverou, E, Panagiotakos, DB, Kyrou, I, Stefanadis, C, Chrysohoou, C, Georgousopoulou, EN, Skoumas, I, Tousoulis, D, Pitsavos, C, ,
Diabetes/metabolism research and reviews. 2019;(6):e3161
Abstract
BACKGROUND Visceral adiposity index (VAI) is a novel marker of visceral adipose tissue accumulation and dysfunction. The study aim was to explore the association of VAI with the 10-year type 2 diabetes mellitus (T2DM) incidence in apparently healthy individuals and compare its T2DM predictive ability against common anthropometric indices. METHODS In 2001 to 2002, the ATTICA study (Greece) recruited a random sample of 1514 and 1528 CVD-free men (18-87 years old) and women (18-89 years old), respectively. Sociodemographic, lifestyle, clinical, and biochemical characteristics of participants were measured at baseline, and the 10-year follow-up was performed during 2011 to 2012. After excluding participants with diabetes at baseline and participants without complete follow-up information regarding diabetes status and/or baseline VAI values, the working sample consisted of 1049 participants. In this sample, the predictive value of baseline VAI value was studied in relation to 10-year diabetes incidence. RESULTS One hundred thirty-three incident cases of diabetes were documented (10-year incidence: 12.7%). In the fully adjusted model, VAI significantly increased diabetes risk by 22% (OR per 1-unit increase =1.22; 95%CI, 1.09-1.37). Markers of oxidative stress and inflammation were found to, at least partly, mediate this relationship. Also, a moderating effect of menstruation status was revealed among women. VAI showed the highest predictive ability and contributed the most, along with waist-to-height ratio, to the correct classification of participants who developed diabetes. CONCLUSIONS The present findings suggest that VAI may be a useful index for predicting long-term diabetes development and may exhibit better predictive ability to commonly used anthropometric indices.
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Effects of Whole Grain Wheat Bread on Visceral Fat Obesity in Japanese Subjects: A Randomized Double-Blind Study.
Kikuchi, Y, Nozaki, S, Makita, M, Yokozuka, S, Fukudome, SI, Yanagisawa, T, Aoe, S
Plant foods for human nutrition (Dordrecht, Netherlands). 2018;(3):161-165
Abstract
Metabolic syndrome is a risk factor for cardiovascular diseases and has become increasingly common in Japan. Epidemiological studies show inverse associations between intake of whole wheat grains and metabolic syndrome, but few dietary intervention trials have investigated the effect of whole wheat grain consumption. It was investigated whether a diet in which refined wheat bread (RW diet) was substituted by whole grain wheat bread (WW diet) would reduce visceral fat obesity in Japanese subjects. A randomized double-blind placebo-controlled intervention study was conducted in 50 Japanese subjects with body mass index (BMI) ≥ 23 kg/m2. Subjects were randomly assigned WW (WW group) or RW diets (RW group) for 12 weeks. Blood samples and computed tomography scans were obtained every 6th week. The WW group showed decrease (-4 cm2) in visceral fat area (VFA) (p < 0.05), whereas the RW group showed no significant changes. These time-dependent changes were significantly different between the groups. WW diet led to significant and safe reductions in VFA in subjects with BMI ≥ 23 kg/m2. WW diet may contribute to preventing visceral fat obesity.
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The Genetics of Pediatric Nonalcoholic Fatty Liver Disease.
Goyal, NP, Schwimmer, JB
Clinics in liver disease. 2018;(1):59-71
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Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. Severe fibrosis and cirrhosis are potential consequences of pediatric NAFLD and can occur within a few years of diagnosis. Observations suggest that genetics may be a strong modifying factor in the presentation, severity, and natural history of the disease. There is increasing interest in determining at-risk populations based on genetics in the hope of finding genotypes that correlate to NAFLD phenotype. Ultimately, the hope is to be able to tailor therapeutics to genetic predispositions and decrease disease morbidity in children with NAFLD.