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Effects of liraglutide on visceral and ectopic fat in adults with overweight and obesity at high cardiovascular risk: a randomised, double-blind, placebo-controlled, clinical trial.
Neeland, IJ, Marso, SP, Ayers, CR, Lewis, B, Oslica, R, Francis, W, Rodder, S, Pandey, A, Joshi, PH
The lancet. Diabetes & endocrinology. 2021;(9):595-605
Abstract
BACKGROUND Visceral and ectopic fat are key drivers of adverse cardiometabolic outcomes in obesity. We aimed to evaluate the effects of injectable liraglutide 3·0 mg daily on body fat distribution in adults with overweight or obesity without type 2 diabetes at high cardiovascular disease risk. METHODS In this randomised, double-blind, placebo-controlled, phase 4, single centre trial, we enrolled community-dwelling adults, recruited from the University of Texas Southwestern Medical Center, with BMI of at least 30 kg/m2 or BMI of at least 27 kg/m2 with metabolic syndrome but without diabetes and randomly assigned them, in a 1:1 ratio, to 40 weeks of treatment with once-daily subcutaneous liraglutide 3·0 mg or placebo, in addition to a 500 kcal deficient diet and guideline-recommended physical activity counselling. The primary endpoint was percentage reduction in visceral adipose tissue (VAT) measured with MRI. All randomly assigned participants with a follow-up imaging assessment were included in efficacy analyses and all participants who received at least one dose of study drug were included in the safety analyses. The trial is registered on ClinicalTrials.gov: NCT03038620. FINDINGS Between July 20, 2017 and Feb 21, 2020 from 235 participants assessed for eligibility, 185 participants were randomly assigned (n=92 liraglutide, n=93 placebo) and 128 (n=73 liraglutide, n=55 placebo) were included in the final analysis (92% female participants, 37% Black participants, 24% Hispanic participants, mean age 50·2 years (SD 9·4), mean BMI 37·7 kg/m2). Mean change in VAT over median 36·2 weeks was -12·49% (SD 9·3%) with liraglutide compared with -1·63% (SD 12·3%) with placebo, estimated treatment difference -10·86% (95% CI -6·97 to -14·75, p<0·0001). Effects seemed consistent across subgroups of age, sex, race-ethnicity, BMI, and baseline prediabetes. The most frequently reported adverse events were gastrointestinal-related (43 [47%] of 92 with liraglutide and 12 [13%] of 93 with placebo) and upper respiratory tract infections (10 [11%] of 92 with liraglutide and 14 [15%] of 93 with placebo). INTERPRETATION In adults with overweight or obesity at high cardiovascular disease risk, once-daily liraglutide 3·0 mg plus lifestyle intervention significantly lowered visceral adipose tissue over 40 weeks of treatment. Visceral fat reduction may be one mechanism to explain the benefits seen on cardiovascular outcomes in previous trials with liraglutide among patients with type 2 diabetes. FUNDING NovoNordisk.
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Contribution of ultra-processed foods in visceral fat deposition and other adiposity indicators: Prospective analysis nested in the PREDIMED-Plus trial.
Konieczna, J, Morey, M, Abete, I, Bes-Rastrollo, M, Ruiz-Canela, M, Vioque, J, Gonzalez-Palacios, S, Daimiel, L, Salas-Salvadó, J, Fiol, M, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(6):4290-4300
Abstract
BACKGROUND & AIMS Ultra-processed food and drink products (UPF) consumption has been associated with obesity and its-related comorbidities. Excess of visceral fat, which appears with increasing age, has been considered as the culprit contributing to adiposity-associated adverse health outcomes. However, none of previous studies elucidated the link between UPF and directly quantified adiposity and its distribution. We aimed to prospectively investigate the association between concurrent changes in UPF consumption and objectively assessed adiposity distribution. METHODS A subsample of 1485 PREDIMED-Plus participants (Spanish men and women aged 55-75 years with overweight/obesity and metabolic syndrome) underwent body composition measurements. Consumption of UPF at baseline, 6 and 12 months was evaluated using a validated 143-item semi-quantitative Food Frequency Questionnaire. Food items (g/day) were categorized according to their degree of processing using NOVA system. Regional adiposity (visceral fat (in g) and android-to-gynoid fat ratio) and total fat mass (in g) at three time points were measured with dual-energy X-ray absorptiometry (DXA) and were normalized using sex-specific z-scores. The association of changes in UPF consumption, expressed as the percentage of total daily intake (daily g of UPF/total daily g of food and beverage intake∗100), with adiposity changes was evaluated using linear mixed-effects models. RESULTS On average, the consumption of UPF accounted for 8.11% (SD 7.41%) of total daily intake (in grams) at baseline. In multivariable-adjusted model, 10% daily increment in consumption of UPF was associated with significantly (all p-values <0.05) greater accumulation of visceral fat (β 0.09 z-scores, 95% CI 0.05; 0.13), android-to-gynoid fat ratio (0.05, 0.00; 0.09) and total fat (0.09, 0.06; 0.13). CONCLUSION A higher consumption of UPF was associated with greater age-related visceral and overall adiposity accumulation. Further studies are warranted to confirm these results in other populations and settings. TRIAL REGISTRATION The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.
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Visceral Adiposity Index (VAI) in Children and Adolescents with Obesity: No Association with Daily Energy Intake but Promising Tool to Identify Metabolic Syndrome (MetS).
Vizzuso, S, Del Torto, A, Dilillo, D, Calcaterra, V, Di Profio, E, Leone, A, Gilardini, L, Bertoli, S, Battezzati, A, Zuccotti, GV, et al
Nutrients. 2021;(2)
Abstract
(1) Background. Visceral adiposity index (VAI) has been recently identified as a new cardiometabolic risk marker reflecting abdominal fat distribution and dyslipidaemia. The aim of the present paper was to evaluate the relationship between VAI, daily energy intake and metabolic syndrome (MetS) in a cohort of obese Caucasian children and adolescents, aged 8 to 15 years. (2) Methods. Consecutive Italian children and adolescents with obesity, according to World Health Organization were enrolled. Anthropometric parameters and blood pressure were measured. Fasting blood samples have been analyzed for lipids, insulin and glucose levels. MetS was diagnosed using identification and prevention of dietary- and lifestyle-induced health effects in children and infants (IDEFICS) or International Diabetes Federation (IDF) criteria according to age. Homeostatic model assessment index (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), A body shape index (ABSI) and VAI were calculated. Multivariable logistic regression analyses with sex, age and each anthropometric parameter (body mass index (BMI) z-score, ABSI, waist-to-height ratio (WHR)) or VAI was performed to predict MetS. Receiver operation curve (ROC) analysis was used to define the optimal VAI cut-off to identify MetS. Multiple regression was performed to predict the BMI z-score and VAI from daily energy intake after adjusting for age and sex. (3) Results. Six hundred and thirty-seven (313 boys and 324 girls) children and adolescents with obesity with median age 11 (interquartile range 10-13) years were included in the analysis. MetS was diagnosed in 79 patients. VAI correlated with BMI, WHR, ABSI, HOMA-IR, QUICKI, systolic blood pressure, low- and high-density lipoprotein cholesterol, triglycerides and triglycerides-to-HDL ratio (p < 0.050). Optimal VAI cut-off (AUC) values to identify MetS were 1.775 (0.774), 1.685 (0.776) and 1.875 (0.797) in the whole population, boys and girls, respectively. Energy intake was positively associated with BMI z-score but no association was found with VAI. (4) Conclusion. VAI is a promising tool to identify MetS in children and adolescents with obesity and should be used in the management of abdominal obesity together with dietary assessment.
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The Role of Visceral Adiposity Index as Predictor of Metabolic Syndrome in Obese and Nonobese Women with Polycystic Ovary Syndrome.
de Medeiros, SF, de Medeiros, MAS, Barbosa, BB, Yamamoto, MMW
Metabolic syndrome and related disorders. 2021;(1):18-25
Abstract
Background: To evaluate anthropometric-metabolic biomarkers as predictors of metabolic syndrome (MS) in women with polycystic ovary syndrome (PCOS) with and without obesity. Methods: This was an observational cross-sectional study. Patients were classified as nonobese-PCOS (body mass index, BMI <30 kg/m2, n = 385), and obese-PCOS (BMI ≥30 kg/m2, n = 261). The anthropometric parameters waist circumference, waist/hip ratio, lean body mass, fat body mass, visceral adiposity index (VAI), lipid accumulating product, and biomarkers of glucose and lipid metabolisms were compared between groups. Binominal logistic regression analyses were performed to identify predictors of MS. Results: Obesity was diagnosed in 40% of all PCOS women (P < 0.001). Blood pressure and anthropometric abnormalities were significantly more frequent in obese-PCOS women (P < 0.001, for all comparisons). Glucose metabolism markers were higher in obese-PCOS compared with nonobese-PCOS (P < 0.001, for all comparisons). High-density lipoprotein cholesterol was lower in obese group than in nonobese group (1.26 mM vs. 1.08 mM, P < 0.001). MS was found in 23 of 385 (6%) nonobese-PCOS and in 116 of 261 (44.4%) obese-PCOS (P < 0.001). VAI was the best predictor of MS in both nonobese-PCOS (OR = 4.1, 95% CI 1.5-11.1) and obese-PCOS (OR = 12.9, 95% CI 5.7-29.0). Conclusions: MS is more prevalent in PCOS women with obesity. VAI was the strongest predictor of MS in both obese and nonobese PCOS women, and can be applied in clinical practice for early detection of risk for MS and precocious intervention in women with PCOS, particularly in obese women.
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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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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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Metabolic profiling of visceral adipose tissue from obese subjects with or without metabolic syndrome.
Candi, E, Tesauro, M, Cardillo, C, Lena, AM, Schinzari, F, Rodia, G, Sica, G, Gentileschi, P, Rovella, V, Annicchiarico-Petruzzelli, M, et al
The Biochemical journal. 2018;(5):1019-1035
Abstract
Obesity represents one of the most complex public health challenges and has recently reached epidemic proportions. Obesity is also considered to be primarily responsible for the rising prevalence of metabolic syndrome, defined as the coexistence in the same individual of several risk factors for atherosclerosis, including dyslipidemia, hypertension and hyperglycemia, as well as for cancer. Additionally, the presence of three of the five risk factors (abdominal obesity, low high-density lipoprotein cholesterol, high triglycerides, high fasting glucose and high blood pressure) characterizes metabolic syndrome, which has serious clinical consequences. The current study was conducted in order to identify metabolic differences in visceral adipose tissue (VAT) collected from obese (body mass index 43-48) human subjects who were diagnosed with metabolic syndrome, obese individuals who were metabolically healthy and nonobese healthy controls. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analyses were used to obtain the untargeted VAT metabolomic profiles of 481 metabolites belonging to all biochemical pathways. Our results indicated consistent increases in oxidative stress markers from the pathologically obese samples in addition to subtle markers of elevated glucose levels that may be consistent with metabolic syndrome. In the tissue derived from the pathologically obese subjects, there were significantly elevated levels of plasmalogens, which may be increased in response to oxidative changes in addition to changes in glycerolphosphorylcholine, glycerolphosphorylethanolamine glycerolphosphorylserine, ceramides and sphingolipids. These data could be potentially helpful for recognizing new pathways that underlie the metabolic-vascular complications of obesity and may lead to the development of innovative targeted therapies.
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Effect of Oral Paprika Xanthophyll Intake on Abdominal Fat in Healthy Overweight Humans: A Randomized, Double-blind, Placebo-controlled Study.
Kakutani, R, Hokari, S, Nishino, A, Ichihara, T, Sugimoto, K, Takaha, T, Kuriki, T, Maoka, T
Journal of oleo science. 2018;(9):1149-1162
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Abstract
PURPOSE Xanthophylls that exist in various vegetables and fruits have beneficial actions, such as antioxidant activity and an anti-metabolic syndrome effect, and daily intake of xanthophylls could play an important role in preventing lifestyle-related diseases. We investigated whether intake of xanthophylls from red paprika could decrease the abdominal fat area in the healthy overweight volunteers with a body mass index (BMI) ranging from 25 to < 30 kg/m2. METHODS In a randomized, double-blind, placebo-controlled, parallel-group study, 100 healthy volunteers were assigned to oral administration of paprika xanthophyll capsules (containing 9.0 mg of paprika xanthophylls) or placebo capsules for 12 weeks. The primary endpoint was the effect of paprika xanthophyll intake on the abdominal visceral fat area (VFA) as determined by computed tomography. The secondary endpoints were as follows: 1) changes of the abdominal subcutaneous fat area (SFA), total fat area (TFA), and BMI; 2) changes of lipid metabolism parameters, glucose metabolism parameters, and other blood parameters. RESULTS After 12 weeks, VFA was smaller in the paprika xanthophyll group than in the placebo group. In the paprika xanthophyll group, there was a significant decrease of SFA, TFA, and BMI after 12 weeks compared with baseline, and the reduction of SFA, TFA, and BMI was significantly greater in the paprika xanthophyll group than in the placebo group. Moreover, total cholesterol and low-density lipoprotein cholesterol decreased significantly in the paprika xanthophyll group, but not in the placebo group. No adverse effects were caused by intake of paprika xanthophyll capsules. CONCLUSIONS Intake of paprika xanthophylls for 12 weeks significantly reduced the abdominal fat area and BMI in healthy overweight volunteers without causing any adverse effects. These findings suggest that paprika xanthophyll is a safe food ingredient that improves lipid metabolism and reduces abdominal fat. TRIAL REGISTRATION UMIN-CTR UMIN000021529.
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Visceral adiposity and metabolic syndrome after very high-fat and low-fat isocaloric diets: a randomized controlled trial.
Veum, VL, Laupsa-Borge, J, Eng, Ø, Rostrup, E, Larsen, TH, Nordrehaug, JE, Nygård, OK, Sagen, JV, Gudbrandsen, OA, Dankel, SN, et al
The American journal of clinical nutrition. 2017;(1):85-99
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BACKGROUND Different aspects of dietary pattern, including macronutrient and food profiles, may affect visceral fat mass and metabolic syndrome. OBJECTIVE We hypothesized that consuming energy primarily from carbohydrate or fat in diets with similar food profiles would differentially affect the ability to reverse visceral adiposity and metabolic syndrome. DESIGN Forty-six men (aged 30-50 y) with body mass index (in kg/m2) >29 and waist circumference >98 cm were randomly assigned to a very high-fat, low-carbohydrate (VHFLC; 73% of energy fat and 10% of energy carbohydrate) or low-fat, high-carbohydrate (LFHC; 30% of energy fat and 53% of energy carbohydrate) diet for 12 wk. The diets were equal in energy (8750 kJ/d), protein (17% of energy), and food profile, emphasizing low-processed, lower-glycemic foods. Fat mass was quantified with computed tomography imaging. RESULTS Recorded intake of carbohydrate and total and saturated fat in the LFHC and VHFLC groups were 51% and 11% of energy, 29% and 71% of energy, and 12% and 34% of energy, respectively, with no difference in protein and polyunsaturated fatty acids. Mean energy intake decreased by 22% and 14% in the LFHC and VHFLC groups. The diets similarly reduced waist circumference (11-13 cm), abdominal subcutaneous fat mass (1650-1850 cm3), visceral fat mass (1350-1650 cm3), and total body weight (11-12 kg). Both groups improved dyslipidemia, with reduced circulating triglycerides, but showed differential responses in total and low-density lipoprotein cholesterol (decreased in LFHC group only), and high-density lipoprotein cholesterol (increased in VHFLC group only). The groups showed similar reductions in insulin, insulin C-peptide, glycated hemoglobin, and homeostasis model assessment of insulin resistance. Notably, improvements in circulating metabolic markers in the VHFLC group mainly were observed first after 8 wk, in contrast to more acute and gradual effects in the LFHC group. CONCLUSIONS Consuming energy primarily as carbohydrate or fat for 3 mo did not differentially influence visceral fat and metabolic syndrome in a low-processed, lower-glycemic dietary context. Our data do not support the idea that dietary fat per se promotes ectopic adiposity and cardiometabolic syndrome in humans. This study was registered at clinicaltrials.gov as NCT01750021.
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Discriminatory Ability of Visceral Adiposity Index (VAI) in Diagnosis of Metabolic Syndrome: A Population Based Study.
Motamed, N, Khonsari, MR, Rabiee, B, Ajdarkosh, H, Hemasi, GR, Sohrabi, MR, Maadi, M, Zamani, F
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2017;(3):202-207
Abstract
Background Visceral adiposity index (VAI) has been suggested as an index of visceral adiposity. This study was conducted to determine the discriminatory ability of VAI in diagnosis of metabolic syndrome (MetS). Methods and materials We used the data of 5 312 subjects aged 18-74 years of a cohort study conducted among 6 140 individuals aged 10-90 years in Amol, northern Iran. The city population was divided into 16 strata based on gender and age groups in 10-year intervals. The subjects were randomly selected from each stratum. MetS was defined based on National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII), American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) update of Adult Treatment Panel III (ATPIII), International Diabetes Federation (IDF) and joint interim statement (JIS) definitions. The discriminatory ability of VAI and other obesity measures were evaluated using receiver operating characteristic (ROC) curves. Results While waist circumference (WC) showed the highest discriminatory ability for MetS in IDF definition in men (AUC=0.899 [CI=0.888-0.910]), VAI had the greatest discriminatory ability according to other definitions in men and women. The related AUCs of VAI were 0.866 (95%CI: 0.850-0.881), 0.829 (95%CI: 0.813-0.846), 0.859 (95%CI: 0.844-0.873) and 0.876 (95%CI: 0.863-0.889) based on NCEP/ATPIII, AHA/NHLBI update of ATPIII, IDF and JIS definition in men, and also 0.888 (95%CI: 0.875-0.902), 0.894 (95%CI: 0.881-0.907), 0.883 (95%CI: 0.869-0.897) and 0.879 (95%CI: 0.864-0.894) in women, respectively. Conclusion VAI showed an excellent discriminatory ability in diagnosis of MetS. Considering its relatively simple calculation, this index could be suggested as a reliable tool in medical practice.