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1.
Sci Rep ; 14(1): 3012, 2024 02 06.
Article in English | MEDLINE | ID: mdl-38321127

ABSTRACT

Obesity is a complex chronic condition associated with multiple health risks, including visceral obesity, which is particularly detrimental. To gain insight into the mechanisms underlying obesity and its associated pathologies, a novel zebrafish model was established using an innovative high-fat diet (HFD). The primary goal was to induce visceral obesity in zebrafish and study the associated structural changes. To achieve this, a unique HFD consisting of 40% beef fat (HFD40) was developed and supplemented with magnesium aluminometasilicate to improve stability in a high humidity environment. Feeding regimens were initiated for both juvenile (starting at 2 weeks post-fertilization, lasting 18 weeks) and adult zebrafish (3 months post-fertilization, 8 weeks feeding duration). The innovative dietary approach successfully induced visceral obesity in both juvenile and adult zebrafish. This new model provides a valuable tool to study obesity-related pathologies, metabolic syndrome, and potential therapeutic interventions. Most importantly, the low-cost and easy-to-prepare composition of HFD40 was seamlessly incorporated into the water without the need for separation, was readily absorbed by the fish and induced rapid weight gain in the zebrafish population. In conclusion, this study presents a novel HFD40 composition enriched with a high beef fat concentration (40%), which represents a significant advance in the development of an experimental zebrafish model for the study of visceral obesity and associated metabolic changes.


Subject(s)
Diet, High-Fat , Obesity, Abdominal , Animals , Cattle , Obesity, Abdominal/metabolism , Zebrafish , Obesity/metabolism , Weight Gain
2.
J Ethnopharmacol ; 282: 114590, 2022 Jan 10.
Article in English | MEDLINE | ID: mdl-34487844

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Carthamus tinctorius L. (Safflower) has been widely recommended to treat metabolic disorders in traditional herbal medicine in Persia, China, Korea, Japan, and other East-Asian countries. The anti-hypercholesterolemic and antioxidant effects of this plant have been well documented, but its protective effects against Metabolic Syndrome (MetS) have not been fully illustrated. AIM OF THE STUDY: The present study aimed to evaluate the effects of safflower oil on MetS risk factors. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled clinical trial, 67 patients with MetS were administered either divided 8 g safflower oil or placebo daily for 12 weeks. All patients were advised to follow their previous diets and physical activities. RESULTS: Safflower oil resulted in a significant reduction in waist circumference (-2.42 ± 3.24 vs. 0.97 ± 2.53, p<0.001), systolic blood pressure (-8.80 ± 9.77 vs. -2.26 ± 8.56, p = 0.021), diastolic blood pressure (-3.53 ± 7.52 vs. -0.70 ± 6.21, p = 0.041), fasting blood sugar (-5.03 ± 10.62 vs. 2.94 ± 7.57, p = 0.003), and insulin resistance (-0.59 ± 1.43 vs. 0.50 ± 1, p = 0.012), but an increase in adiponectin level (0.38 ± 0.99 vs. -0.09 ± 0.81, p = 0.042) in the treatment group in comparison to the placebo group. The results revealed a direct relationship between leptin level and Body Mass Index (BMI) in both groups (p<0.001). In addition, increase in BMI resulted in a non-significant decrease in adiponectin level in both groups. Moreover, no significant difference was observed between the two groups regarding lipid profiles, leptin serum level, serum creatinine concentration, and other outcomes. CONCLUSION: Safflower oil without lifestyle modification improved abdominal obesity, blood pressure, and insulin resistance in patients with MetS.


Subject(s)
Blood Glucose/analysis , Blood Pressure Determination , Carthamus tinctorius , Metabolic Syndrome , Obesity, Abdominal , Safflower Oil/administration & dosage , Adiponectin/blood , Adult , Anticholesteremic Agents/administration & dosage , Antioxidants/administration & dosage , Blood Pressure Determination/methods , Blood Pressure Determination/statistics & numerical data , Body Mass Index , Double-Blind Method , Drug Monitoring/methods , Female , Humans , Insulin Resistance , Male , Medicine, Persian/methods , Metabolic Syndrome/drug therapy , Metabolic Syndrome/metabolism , Metabolic Syndrome/physiopathology , Obesity, Abdominal/diagnosis , Obesity, Abdominal/drug therapy , Obesity, Abdominal/metabolism , Phytotherapy/methods , Treatment Outcome
3.
Front Endocrinol (Lausanne) ; 12: 696977, 2021.
Article in English | MEDLINE | ID: mdl-34220720

ABSTRACT

Purpose: Elevated postprandial glycaemia [PPG] increases the risk of cardiometabolic complications in insulin-resistant, centrally obese individuals. Therefore, strategies that improve PPG are of importance for this population. Consuming large doses of whey protein [WP] before meals reduces PPG by delaying gastric emptying and stimulating the secretion of the incretin peptides, glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide 1 [GLP-1]. It is unclear if these effects are observed after smaller amounts of WP and what impact central adiposity has on these gastrointestinal processes. Methods: In a randomised-crossover design, 12 lean and 12 centrally obese adult males performed two 240 min mixed-meal tests, ~5-10 d apart. After an overnight fast, participants consumed a novel, ready-to-drink WP shot (15 g) or volume-matched water (100 ml; PLA) 10 min before a mixed-nutrient meal. Gastric emptying was estimated by oral acetaminophen absorbance. Interval blood samples were collected to measure glucose, insulin, GIP, GLP-1, and acetaminophen. Results: WP reduced PPG area under the curve [AUC0-60] by 13 and 18.2% in the centrally obese and lean cohorts, respectively (both p <0.001). In both groups, the reduction in PPG was accompanied by a two-three-fold increase in GLP-1 and delayed gastric emptying. Despite similar GLP-1 responses during PLA, GLP-1 secretion during the WP trial was ~27% lower in centrally obese individuals compared to lean (p = 0.001). In lean participants, WP increased the GLP-1ACTIVE/TOTAL ratio comparative to PLA (p = 0.004), indicative of reduced GLP-1 degradation. Conversely, no treatment effects for GLP-1ACTIVE/TOTAL were seen in obese subjects. Conclusion: Pre-meal ingestion of a novel, ready-to-drink WP shot containing just 15 g of dietary protein reduced PPG in lean and centrally obese males. However, an attenuated GLP-1 response to mealtime WP and increased incretin degradation might impact the efficacy of nutritional strategies utilising the actions of GLP-1 to regulate PPG in centrally obese populations. Whether these defects are caused by an individual's insulin resistance, their obese state, or other obesity-related ailments needs further investigation. Clinical Trial Registration: ISRCTN.com, identifier [ISRCTN95281775]. https://www.isrctn.com/.


Subject(s)
Blood Glucose/metabolism , Gastrointestinal Hormones/metabolism , Obesity, Abdominal/diet therapy , Whey Proteins/pharmacology , Adult , Blood Glucose/drug effects , C-Peptide/blood , Cross-Over Studies , Eating , England , Food, Formulated , Gastric Emptying/physiology , Gastric Inhibitory Polypeptide/blood , Gastric Inhibitory Polypeptide/drug effects , Glucagon/blood , Glucagon-Like Peptide 1/blood , Glucagon-Like Peptide 1/drug effects , Humans , Insulin/blood , Male , Middle Aged , Obesity, Abdominal/blood , Obesity, Abdominal/metabolism , Postprandial Period/drug effects , Thinness/blood , Thinness/metabolism , Whey Proteins/administration & dosage , Young Adult
4.
Eur J Clin Invest ; 51(9): e13538, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33682081

ABSTRACT

BACKGROUND: Selenium deficiency appears to limit antioxidant defense in obese individuals. This study evaluated the association between adiposity indices, selenium status, and oxidative stress in obese women. METHODS: This was a cross-sectional study involving 139 women who were divided into the following two groups: the case group (obese women, n = 63) and the control group (normal-weight women, n = 76). Plasma, erythrocyte, and urinary selenium levels were determined using inductively coupled plasma optical emission spectrometry. Body weight, height, waist circumference, hip circumference and neck circumference were measured. Body mass index, waist/height ratio, conicity index, body fat index, body adiposity index, body circularity index, and visceral adiposity index were calculated. Plasma levels of thiobarbituric acid reactive substances were determined. The erythrocyte glutathione peroxidase activity was determined using an automatic biochemical analyzer and Ransel kit. RESULTS: Obese women had selenium deficiency characterized by reduction in plasma and erythrocyte concentrations (P < .001). The urinary selenium excretion was higher in the case group compared to the control group (P < .001). Adiposity indices values and plasma concentrations of thiobarbituric acid reactive substances were significantly elevated in obese women (P < .001). There was a significant association between adiposity indices and selenium status (P < .001), and between erythrocyte selenium and erythrocyte glutathione peroxidase activity (P < .001). CONCLUSION: Obese women evaluated in the study have reduced plasma and erythrocyte concentrations of selenium and an increased urinary excretion of selenium. The correlation analysis reveals an association between intra-abdominal fat accumulation and selenium metabolism and oxidative stress.


Subject(s)
Erythrocytes/metabolism , Glutathione Peroxidase/metabolism , Obesity/metabolism , Oxidative Stress , Selenium/metabolism , Thiobarbituric Acid Reactive Substances/metabolism , Adult , Body Mass Index , Deficiency Diseases/metabolism , Erythrocytes/enzymology , Female , Humans , Obesity, Abdominal/metabolism , Selenium/blood , Selenium/deficiency , Selenium/urine , Waist Circumference , Waist-Height Ratio
5.
Nutrients ; 12(2)2020 Feb 23.
Article in English | MEDLINE | ID: mdl-32102233

ABSTRACT

In the assessment of the health risk of an obese individual, both the amount of adipose tissue and its distribution and metabolic activity are essential. In adults, the distribution of adipose tissue differs in a gender-dependent manner and is regulated by sex steroids, especially estrogens. Estrogens affect adipocyte differentiation but are also involved in the regulation of the lipid metabolism, insulin resistance, and inflammatory activity of the adipose tissue. Their deficiency results in unfavorable changes in body composition and increases the risk of metabolic complications, which can be partially reversed by hormone replacement therapy. Therefore, the idea of the supplementation of estrogen-like compounds to counteract obesity and related complications is compelling. Phytoestrogens are natural plant-derived dietary compounds that resemble human estrogens in their chemical structure and biological activity. Supplementation with phytoestrogens may confer a range of beneficial effects. However, results of studies on the influence of phytoestrogens on body composition and prevalence of obesity are inconsistent. In this review, we present data from in vitro, animal, and human studies regarding the role of phytoestrogens in adipose tissue development and function in the context of their potential application in the prevention of visceral obesity and related complications.


Subject(s)
Diet , Obesity, Abdominal/drug therapy , Phytoestrogens/therapeutic use , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Adipose Tissue/pathology , Animals , Body Composition/drug effects , Body Weight/drug effects , Humans , Obesity, Abdominal/complications , Obesity, Abdominal/metabolism , Phytoestrogens/classification , Phytoestrogens/pharmacology
6.
Trials ; 21(1): 32, 2020 Jan 06.
Article in English | MEDLINE | ID: mdl-31907080

ABSTRACT

BACKGROUND: The prevalence of central obesity is constantly increasing, and visceral fat is associated with increased production of inflammatory factors and metabolic risk factors. Lutein might retard the development of metabolic disease through its antioxidant and anti-inflammatory properties. Furthermore, epidemiological studies have associated higher dietary intake and serum levels of lutein with decreased adiposity. However, few randomised controlled trials have shown the effects of lutein supplementation on inflammatory biomarkers and metabolic risk factors, especially in adults with central obesity. METHODS: This study will be conducted as a double-blind, parallel placebo-controlled clinical trial in which 120 people who have central obesity, are 18 to 60 years old and are willing to provide informed consent will be randomly assigned to the intervention or placebo group in a 1:1 ratio according to sex, age and waist circumference. The intervention group will receive 10 mg daily lutein supplementation for 12 weeks to explore the effect of lutein supplementation on serum lutein, glycaemic and lipid profiles, inflammatory factors and body composition. Two populations (intention-to-treat population and per-protocol population) will be used in the data analyses. DISCUSSION: Our findings from this trial will contribute to the knowledge of the association between lutein supplementation and inflammatory biomarkers and metabolic risk factors in people with central obesity and will offer a possibility for the prevention of inflammatory diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800018098. Registered on 30 August 2018.


Subject(s)
Dietary Supplements , Inflammation/diagnosis , Lutein/administration & dosage , Obesity, Abdominal/diet therapy , Adolescent , Adult , Biomarkers/blood , Blood Glucose/analysis , Blood Glucose/metabolism , Double-Blind Method , Female , Humans , Inflammation/blood , Inflammation/immunology , Inflammation/prevention & control , Lipid Metabolism/immunology , Lipids/blood , Lutein/blood , Male , Middle Aged , Obesity, Abdominal/blood , Obesity, Abdominal/immunology , Obesity, Abdominal/metabolism , Randomized Controlled Trials as Topic , Risk Factors , Treatment Outcome , Waist Circumference , Young Adult
7.
J Nutr ; 149(6): 1004-1011, 2019 06 01.
Article in English | MEDLINE | ID: mdl-30915471

ABSTRACT

BACKGROUND: Decreased dietary meat may deplete iron stores, as plant-derived iron bioavailability is typically limited. OBJECTIVES: We explored the effect of a low-meat Mediterranean (green-MED) diet, supplemented with Wolffia globosa duckweed (Mankai: rich in protein and iron) as a food source for humans, on iron status. We further examined the iron bioavailability of Mankai in rats. METHODS: Two hundred and ninety-four abdominally obese/dyslipidemic [mean age = 51.1 y; body mass index (kg/m2) = 31.3; 88% men] nonanemic participants were randomly assigned to physical activity (PA), PA + MED diet, or PA + green-MED diet. Both isocaloric MED groups consumed 28 g walnuts/d and the low-meat green-MED group further consumed green tea (800 mL/d) and Mankai (100 g green shake/d). In a complementary animal experiment, after 44 d of an iron deficiency anemia-inducing diet, 50 female rats (age = 3 wk; Sprague Dawley strain) were randomly assigned into: iron-deficient diet (vehicle), or vehicle + iso-iron: ferrous gluconate (FG) 14, Mankai 50, and Mankai 80 versions (1.7 mg · kg-1 · d-1 elemental iron), or FG9.5 and Mankai 50-C version (1.15 mg · kg-1 · d-1 elemental iron). The specific primary aim for both studies was changes in iron homeostasis parameters. RESULTS: After 6 mo of intervention, iron status trajectory did not differ between the PA and PA + MED groups. Hemoglobin modestly increased in the PA + green-MED group (0.23 g/dL) compared with PA (-0.1 g/dL; P < 0.001) and PA + MED (-0.1 g/dL; P < 0.001). Serum iron and serum transferrin saturation increased in the PA + green-MED group compared with the PA group (8.21 µg/dL compared with -5.23 µg/dL and 2.39% compared with -1.15%, respectively; P < 0.05 for both comparisons), as did folic acid (P = 0.011). In rats, hemoglobin decreased from 15.7 to 9.4 mg/dL after 44 d of diet-induced anemia. After depletion treatment, the vehicle-treated group had a further decrease of 1.3 mg/dL, whereas hemoglobin concentrations in both FG and Mankai iso-iron treatments similarly rebounded (FG14: +10.8 mg/dL, Mankai 50: +6.4 mg/dL, Mankai 80: +7.3 mg/dL; FG9.5: +5.1 mg/dL, Mankai 50-C: +7.1 mg/dL; P < 0.05 for all vs. the vehicle group). CONCLUSIONS: In humans, a green-MED low-meat diet does not impair iron homeostasis. In rats, iron derived from Mankai (a green-plant protein source) is bioavailable and efficient in reversal of anemia. This trial was registered at clinicaltrials.gov as NCT03020186.


Subject(s)
Anemia, Iron-Deficiency/diet therapy , Araceae , Diet, Mediterranean , Dietary Supplements , Iron/metabolism , Adult , Anemia, Iron-Deficiency/metabolism , Animals , Araceae/chemistry , Biological Availability , Dietary Supplements/analysis , Disease Models, Animal , Dyslipidemias/diet therapy , Dyslipidemias/metabolism , Female , Homeostasis , Humans , Iron, Dietary/administration & dosage , Iron, Dietary/pharmacokinetics , Male , Middle Aged , Nutritional Physiological Phenomena , Obesity, Abdominal/diet therapy , Obesity, Abdominal/metabolism , Rats , Rats, Sprague-Dawley
8.
Int J Obes (Lond) ; 43(8): 1620-1630, 2019 08.
Article in English | MEDLINE | ID: mdl-30283077

ABSTRACT

BACKGROUND/OBJECTIVES: Ascorbic acid is a known cofactor in the biosynthesis of carnitine, a molecule that has an obligatory role in fatty acid oxidation. Our previous studies have demonstrated that obesity is regulated effectively through peroxisome proliferator-activated receptor α (PPARα)-mediated fatty acid ß-oxidation. Thus, this study aimed to determine whether ascorbic acid can inhibit obesity and nonalcoholic fatty liver disease (NAFLD) in part through the actions of PPARα. DESIGN: After C57BL/6J mice received a low-fat diet (LFD, 10% kcal fat), a high-fat diet (HFD, 45% kcal fat), or the same HFD supplemented with ascorbic acid (1% w/w) (HFD-AA) for 15 weeks, variables and determinants of visceral obesity and NAFLD were examined using metabolic measurements, histology, and gene expression. RESULTS: Compared to HFD-fed obese mice, administration of HFD-AA to obese mice reduced body weight gain, visceral adipose tissue mass, and visceral adipocyte size without affecting food consumption profiles. Concomitantly, circulating ascorbic acid concentrations were significantly higher in HFD-AA mice than in HFD mice. Ascorbic acid supplementation increased the mRNA levels of PPARα and its target enzymes involved in fatty acid ß-oxidation in visceral adipose tissues. Consistent with the effects of ascorbic acid on visceral obesity, ascorbic acid not only inhibited hepatic steatosis but also increased the mRNA levels of PPARα-dependent fatty acid ß-oxidation genes in livers. Similarly, hepatic inflammation, fibrosis, and apoptosis were also decreased during ascorbic acid-induced inhibition of visceral obesity. In addition, serum levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, and LDL cholesterol were lower in HFD-AA-fed mice than in those of HFD-fed mice. CONCLUSIONS: These results suggest that ascorbic acid seems to suppress HFD-induced visceral obesity and NAFLD in part through the activation of PPARα.


Subject(s)
Ascorbic Acid/pharmacology , Diet, High-Fat , Non-alcoholic Fatty Liver Disease/metabolism , Obesity, Abdominal/metabolism , PPAR alpha/metabolism , Animals , Ascorbic Acid/antagonists & inhibitors , Diet, Fat-Restricted , Dietary Supplements , Fatty Acids/metabolism , Gene Expression , Intra-Abdominal Fat/drug effects , Intra-Abdominal Fat/pathology , Liver/drug effects , Liver/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Non-alcoholic Fatty Liver Disease/genetics , Obesity, Abdominal/genetics , Oxidation-Reduction/drug effects , PPAR alpha/genetics , Weight Gain/drug effects
9.
Nutrients ; 10(8)2018 Jul 27.
Article in English | MEDLINE | ID: mdl-30060502

ABSTRACT

Obesity can lead to pathological growth of adipocytes by inducing inflammation and oxidative stress. Genistein could be a potential candidate for the treatment of obesity due to its antioxidant properties. Specific kits were used to examine the effects of genistein vs adiponectin on human visceral pre-adipocytes differentiation, cell viability, mitochondrial membrane potential, and oxidative stress in pre-adipocytes and in white/brown adipocytes. Western Blot was performed to examine changes in protein activation/expression. Genistein increased human visceral pre-adipocytes differentiation and browning, and caused a dose-related improvement of cell viability and mitochondrial membrane potential. Similar effects were observed in brown adipocytes and in white adipocytes, although in white cells the increase of cell viability was inversely related to the dose. Moreover, genistein potentiated AMP-activated protein kinase (AMPK)/mitofusin2 activation/expression in pre-adipocytes and white/brown adipocytes and protected them from the effects of hydrogen peroxide. The effects caused by genistein were similar to those of adiponectin. The results obtained showed that genistein increases human visceral pre-adipocytes differentiation and browning, protected against oxidative stress in pre-adipocytes and white/brown adipocytes through mechanisms related to AMPK-signalling and the keeping of mitochondrial function.


Subject(s)
Adipocytes/drug effects , Antioxidants/pharmacology , Genistein/pharmacology , Glycine max/chemistry , Intra-Abdominal Fat/drug effects , Obesity, Abdominal/metabolism , Oxidative Stress/drug effects , 3T3-L1 Cells , AMP-Activated Protein Kinases/metabolism , Adipocytes/cytology , Adipocytes/metabolism , Adipocytes, Brown/drug effects , Adipocytes, Brown/metabolism , Adipocytes, White/drug effects , Adipocytes, White/metabolism , Adiponectin/metabolism , Animals , Cell Differentiation , Cell Survival , GTP Phosphohydrolases/metabolism , Humans , Hydrogen Peroxide/metabolism , Intra-Abdominal Fat/cytology , Intra-Abdominal Fat/metabolism , Mice , Mitochondria/drug effects , Mitochondrial Proteins/metabolism , Obesity, Abdominal/prevention & control , Phytotherapy , Plant Extracts/pharmacology , Signal Transduction , Uncoupling Protein 1/metabolism
10.
J Nutr ; 148(4): 573-580, 2018 04 01.
Article in English | MEDLINE | ID: mdl-29659963

ABSTRACT

Background: Recent evidence suggests that the association between dietary saturated fatty acids (SFAs) and coronary artery disease risk varies according to food sources. How SFAs from butter and cheese influence HDL-mediated cholesterol efflux capacity (CEC), a key process in reverse cholesterol transport, is currently unknown. Objective: In a predefined secondary analysis of a previously published trial, we have examined how diets rich in SFAs from either cheese or butter influence HDL-mediated CEC, compared with diets rich in either monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs). Methods: In a randomized crossover controlled consumption trial, 46 men and women with abdominal obesity consumed 5 isocaloric diets, each for 4 wk. Two diets were rich in SFAs either from cheese (CHEESE) or butter (BUTTER) [12.4-12.6% of energy (%E) as SFAs, 32%E as fat, 52%E as carbohydrates]. In 2 other diets, SFAs (5.8%E) were replaced with either MUFAs from refined olive oil (MUFA) or PUFAs from corn oil (PUFA). Finally, a lower fat and carbohydrate diet was used as a control (5.8%E as SFAs, 25.0%E as fat, 59%E as carbohydrates; CHO). Post-diet HDL-mediated CEC was determined ex vivo using radiolabelled J774 macrophages incubated with apolipoprotein B-depleted serum from the participants. Results: Mean (±SD) age was 41.4 ± 14.2 y, and waist circumference was 107.6 ± 11.5 cm in men and 94.3 ± 12.4 cm in women. BUTTER and MUFA increased HDL-mediated CEC compared with CHEESE (+4.3%, P = 0.026 and +4.7%, P = 0.031, respectively). Exploring the significant diet × sex interaction (P = 0.044) revealed that the increase in HDL-mediated CEC after BUTTER compared with CHEESE was significant among men (+6.0%, P = 0.047) but not women (+2.9%, P = 0.19), whereas the increase after MUFA compared with CHEESE was significant among women (+9.1%, P = 0.008) but not men (-0.6%, P = 0.99). Conclusion: These results provide evidence of a food matrix effect modulating the impact of dairy SFAs on HDL-mediated CEC with potential sex-related differences that deserve further investigation. This trial was registered at clinicaltrials.gov as NCT02106208.


Subject(s)
Adult , Butter , Cheese , Cholesterol, HDL/metabolism , Diet , Fatty Acids/pharmacology , Obesity, Abdominal/metabolism , Apolipoproteins B/metabolism , Butter/adverse effects , Cheese/adverse effects , Cholesterol/blood , Corn Oil/metabolism , Coronary Artery Disease/etiology , Coronary Artery Disease/metabolism , Cross-Over Studies , Dietary Fats/administration & dosage , Dietary Fats/adverse effects , Dietary Fats/metabolism , Dietary Fats/pharmacology , Fatty Acids/administration & dosage , Fatty Acids/metabolism , Fatty Acids, Unsaturated/administration & dosage , Fatty Acids, Unsaturated/metabolism , Fatty Acids, Unsaturated/pharmacology , Feeding Behavior , Female , Humans , Macrophages/drug effects , Macrophages/metabolism , Male , Middle Aged , Obesity, Abdominal/complications , Olive Oil/metabolism , Risk Factors , Waist Circumference
11.
Mol Nutr Food Res ; 61(11)2017 11.
Article in English | MEDLINE | ID: mdl-28699236

ABSTRACT

SCOPE: Piperonal is an aromatic compound found in vanilla and has a floral odor resembling vanillin. This study was aimed to test whether piperonal attenuates visceral adiposity induced by a high-fat diet (HFD) in mice and to explore the underlying molecular mechanisms. METHODS AND RESULTS: Male C57BL/6N mice were fed a normal diet, HFD, or 0.05% piperonal-supplemented HFD (PSD) for 10 weeks. PSD-fed mice showed attenuation of body weight gain, total visceral fat pad weights, and plasma lipid levels compared to HFD-fed mice. Piperonal supplementation of the HFD increased the mRNA expression of certain isotypes of adenylate cyclase (Adcy) and protein kinase A (PKA) in the white adipose tissue (WAT) of mice. The adipogenesis-related genes were downregulated, whereas fatty acid oxidation- and thermogenesis-related genes were upregulated in the WAT of PSD-fed mice compared to those in HFD-fed mice. Piperonal directly activated Adcy by decreasing the Km for its substrate (ATP) in plasma membranes prepared from the WAT of mice. Furthermore, piperonal-induced inhibition of adipocyte differentiation and elevation of Adcy and PKA activities in 3T3-L1 cells were abrogated by an Adcy inhibitor. CONCLUSION: The anti-adipogenic effect of piperonal in mice fed the high-fat diet appears to be associated with increased Adcy-PKA signaling in WAT.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Adenylyl Cyclases/metabolism , Adiposity , Anti-Obesity Agents/therapeutic use , Benzaldehydes/therapeutic use , Benzodioxoles/therapeutic use , Intra-Abdominal Fat/pathology , Obesity, Abdominal/prevention & control , 3T3-L1 Cells , AMP-Activated Protein Kinases/genetics , Adenylyl Cyclase Inhibitors/pharmacology , Adenylyl Cyclases/chemistry , Adenylyl Cyclases/genetics , Adipogenesis/drug effects , Adiposity/drug effects , Animals , Anti-Obesity Agents/metabolism , Benzaldehydes/metabolism , Benzodioxoles/metabolism , Diet, High-Fat/adverse effects , Dietary Supplements , Gene Expression Regulation, Enzymologic/drug effects , Intra-Abdominal Fat/drug effects , Intra-Abdominal Fat/enzymology , Intra-Abdominal Fat/metabolism , Isoenzymes/antagonists & inhibitors , Isoenzymes/chemistry , Isoenzymes/genetics , Isoenzymes/metabolism , Male , Mice , Mice, Inbred C57BL , Obesity, Abdominal/etiology , Obesity, Abdominal/metabolism , Obesity, Abdominal/pathology , Random Allocation , Signal Transduction/drug effects , Specific Pathogen-Free Organisms , Thermogenesis/drug effects
12.
Molecules ; 22(7)2017 Jun 29.
Article in English | MEDLINE | ID: mdl-28661446

ABSTRACT

Here, the effects of consuming polyphenol-rich olive products, including olive leaves, their crude extract, and extra virgin olive oil, on aspects of the metabolic syndrome are reviewed. We have sought to summarize the available scientific evidence from dietary intervention trials demonstrating a role for these phytochemicals in ameliorating aberrant glucose metabolism, high blood pressure and elevated blood lipids, and we discuss the potential mechanisms underpinning these observations. Searches for relevant literature published in English were conducted via PubMed and Science Direct. Based on published dietary intervention studies, there is convincing evidence to show that olive polyphenols, independently of olive lipids, reduce risk factors for metabolic syndrome, in particular by improving blood sugar and blood pressure control, and in reducing low density lipoprotein oxidation. There is more limited evidence to suggest that the consumption of olive polyphenols or related products can reduce body weight and visceral fat or impede weight gain, and similarly there are some limited data suggesting improved lipid profiles. There is some mechanistic data to support observations made in human volunteers, but further work is needed in this area. The consumption of olive polyphenols within the context of a healthy pattern of food intake may, in part, explain the reduced risk of metabolic disease associated with adherence to the Mediterranean diet.


Subject(s)
Diet , Metabolic Syndrome/etiology , Olea/chemistry , Plant Extracts , Polyphenols , Animals , Diet, Mediterranean , Disease Susceptibility , Dyslipidemias/epidemiology , Dyslipidemias/etiology , Dyslipidemias/metabolism , Humans , Hypertension/epidemiology , Hypertension/etiology , Hypertension/metabolism , Lipid Metabolism , Metabolic Syndrome/epidemiology , Metabolic Syndrome/metabolism , Obesity, Abdominal/epidemiology , Obesity, Abdominal/etiology , Obesity, Abdominal/metabolism , Olea/metabolism , Olive Oil/analysis , Olive Oil/chemistry , Plant Extracts/analysis , Plant Extracts/chemistry , Polyphenols/analysis , Polyphenols/chemistry , Risk Factors
13.
Zhen Ci Yan Jiu ; 41(5): 451-6, 2016 Oct 25.
Article in Chinese | MEDLINE | ID: mdl-29071948

ABSTRACT

OBJECTIVE: To evaluate the efficacy of electroacupuncture (EA) therapy on abdominal fat in obese women by using magnetic resonance imaging(MRI). METHODS: Thirty abdominal obesity women patients were randomly divided into control group (n=15) and EA group (n=15). The obesity patients of the control group did not receive any treatment for weight reduction, and those of the EA group were treated by EA stimulation of bilateral Neiting (ST 44), Fenglong (ST 40), Zusanli (ST 36), Huaroumen (ST 24), Tianshu (ST 25), Wailing (ST 26), Shuidao (ST 28), Fujie (SP 14), Daheng (SP 13), etc. for 25 min, once every other day, 3 times per week for 3 months. The patient's body weight, height, waist circumference (WC) were mea-sured with different devices, and the body mass index (BMI) was calculated, and the subcutaneous adipose tissue thickness at the inferior edges of L4, L5 and S3 and the superior edge of the pubic symphysis and the total abdominal fat volume between the L4 and S3 levels were detected using MRI systems before and after the treatment. RESULTS: The effects of the EA group were significantly superior to those of the control group in lowering difference values (between pre- and post-treatment) of BMI, WC and subcutaneous adipose tissue thickness at the levels of the inferior edges of L4, L5, S3 and the superior edge of the pubic symphysis(all P<0.01)and in reducing total abdominal fat volume between L4 and S3 (all P<0.01). After the treatment, the subcutaneous adipose tissue thickness at the superior edge of the pubic symphysis (P<0.01) and the total abdominal fat volume between L4 and S3 (P<0.05) were significantly decreased in the EA group compared to pre-treatment. There were no significant differences between post- and pre-treatment in BMI, WC, subcutaneous adipose tissue thickness at the levels of the L4, L5 and S3 in both EA and control groups and in the subcutaneous adipose tissue thickness at the level of the superior edge of the pubic symphysis and the total abdominal fat volume between L4 and S3 in the control group (P>0.05). CONCLUSIONS: EA intervention can effectively reduce abdominal fat in obese women based on the evaluation of MRI.


Subject(s)
Electroacupuncture , Obesity, Abdominal/therapy , Abdominal Fat/diagnostic imaging , Abdominal Fat/metabolism , Adult , Female , Humans , Magnetic Resonance Imaging , Obesity, Abdominal/diagnostic imaging , Obesity, Abdominal/metabolism , Treatment Outcome , Young Adult
14.
Clin Nutr ; 35(2): 422-427, 2016 Apr.
Article in English | MEDLINE | ID: mdl-25823387

ABSTRACT

BACKGROUND: Studies examining the dynamics of the thermic effect of feeding (TEF) of specific food items and the relationship of TEF to visceral adiposity are limited. METHODS: We measured resting energy expenditure (REE) and early-TEF (40-min postprandial, e-TEF) after 8-h fast by indirect calorimetry in 40 obese men, and imaged abdominal fat tissues by magnetic resonance imaging. Each participant was examined on two occasions, 3-weeks apart. At each examination we measured fasting REE and then postprandial REE following the isocaloric [∼380 kcal] consumption of either 56 gr walnuts [(8% carbohydrates; 84% fat, of which 72% polyunsaturated fat)], or 5-slices (150gr) of whole-grain bread (48% carbohydrates; 32% fat). e-TEF was calculated as the area under the curve between the fasting and postprandial tests. RESULTS: Participants had a mean age of 45 ± 8 years, body-mass-index (BMI) = 31.1 ± 3.8 kg/m(2), total abdominal fat area = 901.4 ± 240 cm(2), visceral fat area (VAT) = 260 ± 102.9 cm(2), fasting REE = 1854 ± 205 kcal, REE/kg = 19.39 ± 1.73 kcal/kg, and respiratory quotient (RQ, CO2 eliminated/O2 consumed) = 0.82 ± 0.04. Individuals who exhibited increased e-TEF (top ΔAUC median) to bread had higher VAT (299 cm(2) vs. 223 cm(2); p = 0.024) and higher BMI (32.4 kg/m(2) vs. 30.0 kg/m(2); p = 0.013), compared to their peers with the lower e-TEF response (ΔAUC below median). As expected, postprandial e-TEF was higher after whole-grain bread consumption [ΔAUC = +14 kcal/40min] compared to walnuts [ΔAUC = -2 kcal/40 min; p < 0.001]. CONCLUSIONS: Higher early thermic effect of high-carbohydrate food, likely reflecting digestion, early absorption and/or sympathetic tone (rather than metabolic utilization (oxidation)), associates with visceral adiposity. Future studies are required to determine if this association represents an added causality between early carbohydrate processing and visceral fat accumulation.


Subject(s)
Adiposity , Dietary Carbohydrates/administration & dosage , Energy Intake , Obesity, Abdominal/metabolism , Thermogenesis , Adult , Basal Metabolism , Body Mass Index , Body Weight , Calorimetry, Indirect , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Dietary Fats/administration & dosage , Fatty Acids, Unsaturated/administration & dosage , Humans , Male , Middle Aged , Postprandial Period , Triglycerides/blood , Waist Circumference , Whole Grains
15.
Explore (NY) ; 11(5): 401-6, 2015.
Article in English | MEDLINE | ID: mdl-26256500

ABSTRACT

Herbal medicines have received attention as antiabdominal obesity agents. We present a series of 13 cases that demonstrate the positive effect of the herbal complex Hwang-Ryun-Haedok-Tang (HRHT; Tsumura, Tokyo, Japan) on weight and abdominal fat control in patients with abdominal obesity. We treated 13 patients with abdominal obesity treated for 54.46 ± 18.07 days with 5.0 g of HRHT daily. To evaluate the treatment, the morphometric (i.e., waist circumstance, weight, body fat) and biochemical parameters were measured once monthly. After HRHT therapy, the waist circumstance decreased from 91.96 ± 7.99 cm to 87.12 ± 8.09 cm (paired t test, P < .001) and the weight decreased from 78.09 ± 14.35 kg (average ± standard deviation) to 75.72 ± 14.60 kg (paired t test, P < .001). All 13 (100%) patients had low waist circumstances after treatment. Overall, 12 (92.3%) of the 13 patients had a lower weight and body mass index. In the present study, we showed the clinical effects of HRHT on waist circumstance, weight, body mass index, and body fat in patients with abdominal obesity. Further clinical studies investigating the effects of HRHT are needed.


Subject(s)
Adipose Tissue/metabolism , Body Mass Index , Body Weight/drug effects , Drugs, Chinese Herbal/therapeutic use , Obesity, Abdominal/drug therapy , Phytotherapy , Waist Circumference/drug effects , Adult , Coptis , Drugs, Chinese Herbal/pharmacology , Female , Gardenia , Humans , Male , Middle Aged , Obesity, Abdominal/metabolism , Phellodendron , Scutellaria , Young Adult
16.
Pharm Biol ; 53(2): 301-12, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25243869

ABSTRACT

CONTEXT: The herbal composition Gyeongshingangjeehwan 18 (GGEx18) extracted from Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae) is traditionally used as an anti-obesity drug by local clinics in Korea. OBJECTIVE: This study investigates the effects of GGEx18 on visceral obesity and insulin resistance and determines the molecular mechanisms involved in this process. MATERIALS AND METHODS: After C57BL/6J mice were fed a high-fat diet supplemented with GGEx18 (125, 250, and 500 mg/kg) for 8 weeks and 3T3-L1 adipocytes were treated with GGEx18 (0.1, 1, and 10 µg/ml); variables and determinants of visceral obesity and insulin resistance were measured using in vivo and in vitro approaches. RESULTS: Administration of GGEx18 to obese mice decreased visceral adipose tissue weight with an ED50 value of 232 mg/kg. 3T3-L1 adipocytes treated with GGEx18 showed a reduction in lipid accumulation with an ED50 value of 0.7 µg/ml. GGEx18 significantly increased the expression of fatty acid oxidation genes, including adiponectin, AMPKs, PPARα and its target enzymes, and CPT-1, in both mesenteric adipose tissues and 3T3-L1 cells. However, GGEx18 treatment decreased the mRNA levels of adipocyte marker genes such as PPARγ, aP2, TNFα, and leptin. GGEx18 normalized hyperglycemia and hyperinsulinemia in obese mice. Blood glucose levels of GGEx18-treated mice were significantly reduced during oral glucose tolerance tests compared with obese controls. DISCUSSION AND CONCLUSION: These results suggest that GGEx18 may treat visceral obesity and visceral obesity-related insulin resistance by upregulating the visceral adipose expression of fatty acid oxidative genes.


Subject(s)
Anti-Obesity Agents/pharmacology , Ephedra sinica/chemistry , Fatty Acids/metabolism , Gene Expression/drug effects , Insulin Resistance , Intra-Abdominal Fat/metabolism , Laminaria/chemistry , Obesity, Abdominal/drug therapy , Plant Preparations/pharmacology , Rheum/chemistry , 3T3-L1 Cells , AMP-Activated Protein Kinases/genetics , Adipocytes/drug effects , Adipocytes/metabolism , Adiponectin/genetics , Animals , Anti-Obesity Agents/isolation & purification , Cell Size , Fatty Acids/genetics , Male , Mice , Mice, Inbred C57BL , Obesity, Abdominal/metabolism , Oxidation-Reduction , Plant Extracts , Plant Preparations/isolation & purification , Up-Regulation
17.
Nutr Metab Cardiovasc Dis ; 25(1): 52-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25240692

ABSTRACT

BACKGROUND AND AIMS: Little is known about the effect of various dietary fatty acids on pro- and anti-inflammatory processes. We investigated the effect of 5 oils containing various amounts of alpha-linolenic acid (ALA), linoleic acid (LA), oleic acid (OA) and docosahexaenoic acid (DHA) on plasma inflammatory biomarkers and expression levels of key inflammatory genes and transcription factors in whole blood cells. METHODS AND RESULTS: In a randomized, crossover controlled nutrition intervention, 114 adult men and women with abdominal obesity and at least one other criterion for the metabolic syndrome consumed 5 experimental isoenergetic diets for 4 weeks each, separated by 4-week washout periods. Each diet provided 60 g/3000 kcal of different oils: 1) control corn/safflower oil blend (CornSaff; LA-rich), 2) flax/safflower oil blend (FlaxSaff; ALA-rich), 3) conventional canola oil (Canola; OA-rich), 4) high oleic canola oil (CanolaOleic; highest OA content), 5) DHA-enriched high oleic canola oil (CanolaDHA; OA- and DHA-rich). Gene expression in whole blood cells was assessed in a subset of 62 subjects. CanolaDHA increased plasma adiponectin concentrations compared with the control CornSaff oil treatment (+4.5%, P = 0.04) and FlaxSaff (+6.9%, P = 0.0008). CanolaDHA also reduced relative expression levels of interleukin (IL)1B compared with CornSaff and Canola (-11% and -13%, respectively, both P = 0.03). High-sensitivity C-reactive protein concentrations were lower after Canola than after FlaxSaff (-17.8%, P = 0.047). CONCLUSION: DHA-enriched canola oil exerts anti-inflammatory effects compared with polyunsaturated fatty acids from plant sources.


Subject(s)
Adiponectin/agonists , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Docosahexaenoic Acids/therapeutic use , Fatty Acids, Monounsaturated/therapeutic use , Inflammation Mediators/antagonists & inhibitors , Metabolic Syndrome/prevention & control , Obesity, Abdominal/diet therapy , Adiponectin/blood , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/analysis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Biomarkers/blood , Biomarkers/metabolism , Blood Cells/immunology , Blood Cells/metabolism , Body Mass Index , Canada/epidemiology , Cross-Over Studies , Docosahexaenoic Acids/analysis , Double-Blind Method , Fatty Acids, Monounsaturated/chemistry , Female , Food, Fortified , Gene Expression Regulation , Humans , Inflammation Mediators/blood , Inflammation Mediators/metabolism , Male , Metabolic Syndrome/epidemiology , Metabolic Syndrome/etiology , Middle Aged , Obesity, Abdominal/immunology , Obesity, Abdominal/metabolism , Obesity, Abdominal/physiopathology , Pennsylvania/epidemiology , Rapeseed Oil , Risk , Young Adult
18.
Zhen Ci Yan Jiu ; 40(6): 484-8, 2015 Dec.
Article in Chinese | MEDLINE | ID: mdl-26887212

ABSTRACT

OBJECTIVE: To evaluate the efficacy of acupuncture therapy in decreasing visceral fat thickness(VFT) in patients with simple central obesity. METHODS: Sixty patients with simple central obesity (syndrome of stomach and intestinal excessive heat) were randomly divided into control and acupuncture groups. Patients of the control group were treated with diet control and physical exercise procedure (basic treatment) for 6 months, and those of the acupuncture group treated with basic treatment combined with acupuncture stimulation of main acupoints Shuifen (CV 9), Yinjiao (CV 7), and bilateral Tianshu (ST 25), Huaroumen (ST 24) and bilateral Wailing (ST 26), etc., in combination with electroacupuncture (EA, 50- 100 Hz, 1- 5 mA) of bilateral ST 25, CV 9 and CV 7 for 30 min, once every other day for 3 months. The VFT (1 cm above the umbilicus) was detected by using an ultrasonic diagnosis instrument, and the body mass index (BMI, body weight/height(2)), and waist circumfe-rence (WC) were measured before treatment, 3 and 6 months after the treatment, respectively. RESULTS: Following 3 and 6 months' treatment, the VFT, BMI and WC of both groups were significantly decreased (P<0.01), and the effects of the acupuncture group were significantly superior to those of the control group in lowering VFT [(51.5 ± 6.5) mm vs (48.3 ± 4.7) mm)] and WC [(88.2 ± 3.6)cm vs (85.9 ± 4.3)cm] 6 months' after the treatment (P<0.05). There was no significant difference between the control and acupuncture groups in BMI fowllowing 6 months' treatment [(31.0 ± 4.3) vs (30.1 ± 3.2), P>0.05]. CONCLUSION: Acupuncture intervention combined with diet control and physical exercise can effectively decrease VFT and WC in simple central obesity patients. VFT is a sensitive and better parameter for evaluating the effect of obesity treatment.


Subject(s)
Acupuncture Therapy , Obesity, Abdominal/therapy , Acupuncture Points , Adolescent , Adult , Aged , Body Mass Index , Electroacupuncture , Female , Humans , Intra-Abdominal Fat/metabolism , Male , Middle Aged , Obesity, Abdominal/metabolism , Obesity, Abdominal/physiopathology , Waist-Hip Ratio , Young Adult
19.
Zhongguo Zhong Yao Za Zhi ; 39(11): 2081-5, 2014 Jun.
Article in Chinese | MEDLINE | ID: mdl-25272847

ABSTRACT

OBJECTIVE: To investigate the efficacy mechanisme of chicory extract interventing abdominal obesity rat from the aspect of gut bacteria. METHOD: Male SD rats were randomly divided into five groups, namely the normal group, model group, large and small dose group of chicory and the fenofibrate group. Normal group was given deionized water, the other group was given fructose water and give the medical treatment of chicory and fenofibrate. Assay triglycerides, total cholesterol, LDL and HDL by biochemical methods and measure body weight and abdominal circumference and microscopicly observe the count changes of gut bacteria through real-time PCR method. RESULT: Compared with normal group, the triglyceride level and abdominal circumference were significantly higher (P < 0.05), weight and high-density lipoprotein increased but no significant changes and E. coli, lactobacillus increased significantly. Compared with model group, chicory extract large and small dose group and the fenofibrate group can significantly reduce triglyceride levels (P < 0.05), reduce the number of E. coli and Lactobacillus and increase the number of bifidobacteria. The fenofibrate group can significantly reduce total cholesterol and high-density lipoprotein levels. CONCLUSION: The chicory's treatment effect on abdominal obesity is significant. The efficacy mechanisme intervention abdominal obesity may be related to the reduction of the number of lactic acid bacteria and E. coli and the increase of bifidobacteria.


Subject(s)
Bacteria/isolation & purification , Cichorium intybus/metabolism , Gastrointestinal Tract/microbiology , Microbiota , Obesity, Abdominal/metabolism , Obesity, Abdominal/microbiology , Plant Extracts/metabolism , Animals , Bacteria/classification , Bacteria/genetics , Biodiversity , Cichorium intybus/chemistry , Cholesterol/metabolism , Humans , Male , Rats , Rats, Sprague-Dawley , Triglycerides/metabolism
20.
BMC Complement Altern Med ; 14: 298, 2014 Aug 13.
Article in English | MEDLINE | ID: mdl-25123680

ABSTRACT

BACKGROUND: Obesity is an important risk factor for cardiovascular and metabolic diseases and could affect mortality rates. Body mass index (BMI) and waist circumference (WC) have been used to classify obesity, and waist-to-hip ratio (WHR) has recently emerged as a discriminator of cardiovascular disease. Sasang constitution (SC) is a kind of well-known traditional Korean medicine: Tae-eumin (TE), Soeumin (SE), Taeyangin (TY) and Soyangin (SY) carrying a different level of susceptibility to chronic diseases. We aimed to examine the prevalence in general and abdominal obesity (AO) using BMI, WC and WHR according to SC in the Korean population. METHODS: A total of 3,348 subjects were recruited from 24 Korean medicine clinics. Obesity was divided into three categories: general obesity by BMI, abdominal obesity by waist circumference (WC AO) and abdominal obesity by waist-to-hip ratio (WHR AO). A Chi-square test was performed to compare prevalence, and logistic regression was conducted to generate odds ratios (ORs) according to SC (p < .05). RESULTS: The prevalence of general obesity was significantly higher in males than in females. The highest prevalence of general obesity, WC AO and WHR AO were all observed in the TE type, and the SY and SE types were followed in order, for both males and females respectively.The TE type was highly associated with increased risk of general obesity (OR = 20.2, 95% CI: 12.4-32.9 in males and OR = 14.3, 95% CI: 10.1-20.2 in females), of WC AO (OR = 10.7, 95% CI: 7.2-15.9 in males and OR = 7.5, 95% CI: 5.8-9.6 in females), and of WHR AO (OR = 4.6, 95% CI: 3.3-6.4 in males and OR = 3.8, 95% CI: 2.9-4.9 in females) compared with the SE type. In addition, after controlling for age, social status and eating habits, the ORs were similar to the crude model according to gender and SC. CONCLUSIONS: This study shows that the prevalence of obesity varies according to SC in the Korean population. In particular, the TE type was highly associated with increased ORs for general obesity, WC AO and WHR AO in both genders.


Subject(s)
Medicine, Korean Traditional , Obesity, Abdominal/epidemiology , Adult , Aged , Body Mass Index , Chronic Disease , Cross-Sectional Studies , Female , Humans , Logistic Models , Male , Middle Aged , Obesity, Abdominal/diagnosis , Obesity, Abdominal/metabolism , Obesity, Abdominal/physiopathology , Prevalence , Republic of Korea/epidemiology , Risk Factors , Waist Circumference , Waist-Hip Ratio , Young Adult
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