Visceral fat accumulation determines postprandial lipemic response, lipid peroxidation, DNA damage, and endothelial dysfunction in nonobese Korean men

Visceral fat has been associated with multiple cardiovascular disease (CVD) risk factors. The aim of this study was to identify anthropometrical measures most closely associated with some well-known CVD risk factors. Because most Asians at risk have normal body mass index (BMI) according to Western standards, we studied healthy nonobese Korean males (n = 102; age: 36.5 ± 0.8 years, BMI: 23.8 ± 0.2 kg/m2). Visceral fat area (VFA) at the fourth lumbar vertebra was associated with increased postprandial triglyceride (TG) response (r = 0.53, P < 0.001) and with plasma malondialdehyde (MDA) (r = 0.36, P < 0.01) and PGF2α (r = 0.24, P < 0.05). When matched for BMI and age, men with high VFA (HVFA) (≥100 cm2; n = 27) had higher blood pressure (P < 0.01), increased consumption of cigarettes (P < 0.01), and lower ratio of energy expenditure to calorie intake (P < 0.01) as compared with low VFA men (<100 cm2; n = 27). Men with HVFA showed higher TG, glucose, and insulin responses following fat and oral glucose tolerance tests respectively higher plasma concentrations of MDA (P < 0.001), urinary PGF2α (P < 0.05), and lymphocytes deoxyribonucleic acid tail moments (P < 0.01). Conversely, HVFA was associated with lower testosterone, insulin-like growth factor-1, and brachial artery flow-mediated dilation (P < 0.001).In conclusion, our data indicate that visceral fat accumulation, even in nonobese men, is a major factor contributing to increased CVD risk. Visceral fat has been associated with multiple cardiovascular disease (CVD) risk factors. The aim of this study was to identify anthropometrical measures most closely associated with some well-known CVD risk factors. Because most Asians at risk have normal body mass index (BMI) according to Western standards, we studied healthy nonobese Korean males (n = 102; age: 36.5 ± 0.8 years, BMI: 23.8 ± 0.2 kg/m2). Visceral fat area (VFA) at the fourth lumbar vertebra was associated with increased postprandial triglyceride (TG) response (r = 0.53, P < 0.001) and with plasma malondialdehyde (MDA) (r = 0.36, P < 0.01) and PGF2α (r = 0.24, P < 0.05). When matched for BMI and age, men with high VFA (HVFA) (≥100 cm2; n = 27) had higher blood pressure (P < 0.01), increased consumption of cigarettes (P < 0.01), and lower ratio of energy expenditure to calorie intake (P < 0.01) as compared with low VFA men (<100 cm2; n = 27). Men with HVFA showed higher TG, glucose, and insulin responses following fat and oral glucose tolerance tests respectively higher plasma concentrations of MDA (P < 0.001), urinary PGF2α (P < 0.05), and lymphocytes deoxyribonucleic acid tail moments (P < 0.01). Conversely, HVFA was associated with lower testosterone, insulin-like growth factor-1, and brachial artery flow-mediated dilation (P < 0.001). In conclusion, our data indicate that visceral fat accumulation, even in nonobese men, is a major factor contributing to increased CVD risk. The most recent figures about the epidemic of obesity and overweight in the US and other industrialized countries are appalling. Thirty-four percent of US adults are considered overweight, and an additional 31 percent are obese. The consequences of this are far beyond the esthetics of the population. Being overweight or obese increases the risk of hypertension, heart disease, stroke, diabetes, and some cancers. In the US alone, 300,000 people die each year due to obesity-related causes, making it the second-leading cause of death after smoking. Asians experience similar risk of obesity-related diseases, but the problem is more insidious, as the risk threshold at which body mass index (BMI) appears to trigger the disease may be much lower for Asians (∼23 kg/m2) than for white populations (30 kg/m2) (1Choo V. WHO reassesses appropriate body-mass index for Asian populations.Lancet. 2002; 360: 235Abstract Full Text Full Text PDF PubMed Scopus (236) Google Scholar). This may result from differences in body frame that affect the relation between body fat and BMI. The population of Korea, similar to other industrialized countries in Asia, is experiencing dramatic and fast changes in dietary and physical activity habits that are the driving force behind the increase in obesity and obesity-related diseases. Korean adults have increased the percent of calories from fat in their diets from 6% in 1969 to 19% in 1998. Despite the greater than 3-fold increase in the dietary fat intake, their daily calorie intake (about 1,950 kcal/d) and BMI (about 22.5 kg/m2) have changed little over the same period (2South Korean Ministry of Health and Welfare Reports on 1969–1998 National Nutrition survey; Report on National Health and Nutrition Survey. Ministry of Health and Welfare, Seoul, South Korea2000Google Scholar). However, these lifestyle changes have dramatically affected the central adipose tissue distribution pattern as reflected by the global increase of waist-hip ratio (WHR). Among Koreans, the mortality rate (per 100,000 of the population) as a result of ischemic heart disease has rapidly increased from 6.8 in 1988 to 13.8 in 1997 (3South Korean National Statistical Office Annual Report on Cause of Death Statistics. National Statistical Office, Seoul, South Korea1999Google Scholar). The increase in cardiovascular disease (CVD) rates is partially related to the rapid increase in the number of elderly subjects; however, the increase of fat intake in Korean parallels also the disease trends (2South Korean Ministry of Health and Welfare Reports on 1969–1998 National Nutrition survey; Report on National Health and Nutrition Survey. Ministry of Health and Welfare, Seoul, South Korea2000Google Scholar, 3South Korean National Statistical Office Annual Report on Cause of Death Statistics. National Statistical Office, Seoul, South Korea1999Google Scholar). These temporal changes suggest that the increase in fat intake and central fat distribution may be partially responsible for the increasing CVD rates in Korea and other neighboring countries. Previous research has shown that adipose tissue distribution is more closely associated with risk of diabetes, hypertension, and hyperlipidemia than total body fat or BMI (4Kissebah A.H. Krakower G.R. Regional adiposity and morbidity.Physiol. Rev. 1994; 74: 761-811Crossref PubMed Scopus (995) Google Scholar). Thus, visceral fat values above 100–130 cm2 represent a strong risk for these metabolic disturbances (5Williams M.J. Hunter G.R. Kekes-Szabo T. Trueth M.S. Snyder S. Berland L. Bladeau T. Intra-abdominal adipose tissue cut-points related to elevated cardiovascular risk in women.Int. J. Obes. 1996; 20: 613-617PubMed Google Scholar, 6Despres J.P. Lamarche B. Effects of diet and physical activity on adiposity and body fat distribution: implications for the prevention of cardiovascular disease.Nutr. Res. Rev. 1993; 6: 137-159Crossref PubMed Scopus (245) Google Scholar). Moreover, both obesity and visceral fat accumulation have been reported to be related with increased postprandial lipemia (7Couillard C. Bergeron N. Prud'homme D. Bergeron J. Tremblay A. Bouchard C. Mauriege P. Despres J.P. Postprandial triglyceride response in visceral obesity in men.Diabetes. 1998; 47: 953-960Crossref PubMed Scopus (245) Google Scholar), an underestimated CVD risk factor. However, it remains uncertain which measure of obesity represents the best predictor of postprandial lipemia response. Moreover, other behavioral factors, such as alcohol consumption, cigarette smoking, or poor eating patterns such as excessive calorie or high fat intake, are also significant determinants of postprandial lipemia, as well as lipid peroxidation, and deoxyribonucleic acid (DNA) damage (8Parks E.J. Recent findings in the study of postprandial lipemia.Curr. Atheroscler. Rep. 2001; 3: 462-470Crossref PubMed Scopus (68) Google Scholar, 9Dhawan A. Mathur N. Seth P.K. The effect of smoking and eating habits on damage in population as in the Res. 2001; PubMed Scopus Google Scholar, B. in PubMed Scopus Google Scholar, B. and implications for 2001; 20: PubMed Scopus Google Scholar, following a in PubMed Scopus Google Scholar, D. B. of alcohol consumption and smoking habits on cardiovascular risk and in healthy Korean Res. 20: Scopus Google Scholar). The of this study to identify the anthropometrical factor most closely associated with on the postprandial lipid response to a fat and to the between this lipid and damage of lymphocytes in of healthy nonobese men according to the anthropometrical factor from our findings to a of the metabolic and behavioral responsible for the rapid increase in CVD mortality in Korea and to for and from to for a study by the Nutrition at in had normal glucose tolerance tests and of was or had of CVD or healthy men as study The for and BMI and was from and the was from the of the postprandial lipemia response was at after an fast of greater than was in the metabolic of a white and The energy from the Korean on from the National in Korea, was the calorie intake from a of the and of calories from In the of the diet was that of a diet with by a number of Koreans, that about of energy from from from and from and in the and BMI was as body in by in and the a of body fat pressure was from the of was for each a to measure fat and from each at the of the lumbar and fourth lumbar from the between and and from the the most was for the area of fat a in the for total fat at the of and between the of and fat area was visceral and fat to fat for and as between the of and and for fat between and blood from the and and and at and after for of glucose, and with and on at the and at to from or to the fat tolerance also to eating or the concentrations of total and on a of and with in the was by an concentrations the for with < or on a and by at a a than the fat tolerance we a glucose in to glucose a glucose after an and and after the glucose and by the National and the Health on to according to their glucose on the and of Report of the on the and of 20: PubMed Scopus Google Scholar). was by a glucose the was by with from was with a response of glucose, and was with the area each response was also with the C. of the 1996; PubMed Scopus Google the following = insulin glucose to measure total with total insulin growth was the from was with the from was after a fast in blood The with and at was with and mass according to the of and D. of the Full Text Full Text PDF Scopus Google and for the of urinary and plasma Scopus Google Scholar). by the A. 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Scopus Google Scholar). and the was with to additional we brachial to and with the by N. of oral of on brachial in men with artery J. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). was to the artery above the in the for in a The of the artery was the and to identify the and brachial artery artery was from the to the between the and the and at on was by and of a the The blood pressure was to for of the brachial artery was the of was as a measure of The brachial artery was to to the after brachial artery was of was and the brachial artery was for the The was as a measure of The percent in by was by the from by the The percent in by was also in the same pressure and heart rate the data as an from intake was with a and a intake data as values from the same data as calorie expenditure was from activity patterns metabolic physical activity for Nutrition for The Scholar), and of metabolic rate for each was with the of Scholar). for for the for our was for normal distribution and values on and as ± to the of the and multiple to postprandial lipid response. of the in of the factor and matched by a year and BMI a to the for tests to differences in for of P < was considered the of the to in this BMI was 23.8 ± with a of to men reported consumption of and These had similar dietary fat intake, physical and of the of nonobese healthy 36.5 ± 23.8 ± ± fat ± pressure ± ± smoking consumption ± intake ± energy expenditure ± calorie intake ± fat from total calorie intake ± tissue at lumbar vertebra ± Visceral ± tissue at fourth lumbar vertebra ± Visceral ± area ± ± ± body mass blood blood TG, waist-hip ± in a body mass blood blood TG, waist-hip ± The values of and visceral fat at and postprandial and of the are shown in that some anthropometrical such as body and adipose tissue distribution and VFA at and with postprandial lipemia, body and adipose tissue distribution associated with plasma MDA fat at and and VFA at showed with urinary of Postprandial lipemia showed significant with plasma MDA = P = data was shown in was associated with postprandial lipemia lipid of age, body fat total triglyceride response and lipid in nonobese healthy visceral fat area at lumbar fat area at lumbar visceral fat area at fourth lumbar fat area at fourth lumbar in a visceral fat area at lumbar fat area at lumbar visceral fat area at fourth lumbar fat area at fourth lumbar on the from the between body fat measures and postprandial we multiple in to identify the most significant anthropometrical predictor of postprandial lipid response. of body alcohol consumption, and cigarette smoking as and postprandial area was the The data in that the most significant predictor of postprandial response was VFA at by total fat area at multiple for nonobese healthy men age, blood fat at of alcohol consumption, and cigarette smoking as and postprandial area as total fat area at lumbar at of and fat at both and lumbar in a total fat area at lumbar at of and fat at both and lumbar the distribution of VFA at in nonobese healthy in of the factor at as high VFA n = 27). 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The area of the was ± Men the HVFA by higher and blood pressure and higher consumption of cigarettes than the Among the had differences in fat area at both and men with HVFA showed higher ratio of visceral to fat area and lower area of compared with with and in of nonobese men matched on the of and BMI but with low high visceral fat ± ± ± ± ± ± < compared with low fat ± ± pressure ± ± < compared with low ± ± < compared with low ± ± smoking < compared with low ± ± < compared with low < compared with low lumbar vertebra fat ± ± < compared with low Visceral fat ± ± < compared with low fat ± ± fat ± ± < compared with low lumbar vertebra fat ± ± < compared with low Visceral fat ± ± < compared with low fat ± ± fat ± ± < compared with low ± ± ± ± ± ± ± ± < compared with low high visceral fat area n = visceral fat VFA < n = ± P < compared with low P < compared with low P < compared with low in a high visceral fat area n = visceral fat VFA < n = ± differences in and however, men by a HVFA showed higher concentrations of TG, total and Moreover, had lower concentrations of and and higher than with glucose tolerance area the for glucose, and higher in nonobese men with HVFA than in with and glucose and responses to a oral glucose tolerance in of nonobese men matched on the of and BMI but with low high visceral fat ± ± < compared with low ± ± < compared with low ± ± ± ± < compared with low ± ± < compared with low ± ± ± ± < compared with low ± ± < compared with low ± ± < compared with low ± ± ± ± < compared with low ± ± < compared with low ± ± area ± ± < compared with low ± ± < compared with low ± ± < compared with low insulin ± ± insulin-like growth n = ± P < compared with low P < compared with low P < compared with low P < compared with low in a insulin-like growth n = ± men with HVFA showed higher concentrations of urinary of PGF2α and plasma MDA than with moments on the in lymphocytes also higher in nonobese men with HVFA as compared with in the In brachial artery at to for and significant differences between and HVFA ± ± P = and for ± ± P = had significant differences in ± and ± however, the HVFA had lower compared with the concentrations of TG, glucose, and insulin and after the tolerance with and the HVFA showed higher concentrations of at the and and greater compared with men in the concentrations at to values men with however, men with concentrations at the higher than values (P = and insulin concentrations at the and and higher in the HVFA than in the Postprandial for glucose, and insulin increased by and respectively as compared with significant differences between the in the of energy intake from and However, men with HVFA showed higher total calorie intake, lower total energy and lower ratio of total energy expenditure to total calorie intake than with total calorie intake and total energy expenditure in of nonobese men matched on and BMI but with low high visceral fat energy ± ± < compared with low calorie ± ± < compared with low ± ± ± ± ± ± ± ± energy total calorie ± ± < compared with low ± P < compared with low P < compared with low in a ± The HVFA had the increased of postprandial and and of compared with However, the significant differences in smoking between the and HVFA we the after for cigarette smoking. The of these a similar pattern to for of VFA at lumbar vertebra on lipid deoxyribonucleic acid and in of nonobese men matched on the of and BMI but with low high insulin deoxyribonucleic flow-mediated significant by in a deoxyribonucleic flow-mediated significant by data that body fat more VFA at the an index of metabolic in obese S. T. S. and body fat 1996; PubMed Scopus Google Scholar), was the major predictor of postprandial lipemia response as in our population of nonobese Moreover, we between HVFA at the as urinary plasma and and glucose tolerance as glucose, and even for with normal HVFA was associated with lifestyle such as higher consumption of cigarettes and lower ratio of total energy expenditure to total calorie intake compared with with such as high blood high lipid and increased of glucose, and insulin following an in with high visceral fat are with a fat by S. T. 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In conclusion, we significant between fat postprandial lipemia, and lipid in nonobese healthy our data that visceral fat accumulation at the is the most significant of postprandial lipid lipid peroxidation, damage of and of in cardiovascular and mortality risk. The behind the between visceral lipid peroxidation, and to be in to has been shown that visceral adipose tissue accumulation at and is associated with that the fat may a A. Prud'homme D. N. P. A. Bergeron J. Despres J.P. of the of 2001; PubMed Scopus Google Scholar, V. and heart is the Full Text Full Text PDF PubMed Scopus Google Scholar), which in lipid S. A. S. C. in obese of and 2002; PubMed Scopus Google Scholar). This increased lipid which has been shown to to M.J. L. and PubMed Google Scholar). Moreover, may also result from visceral obesity of other risk S. of visceral obesity in in healthy overweight J. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). most is the that these have been considered normal by the anthropometrical risk factors. This is with the dramatic increases in CVD rates in Korea in the of significant BMI the greater of fat the major of be the of visceral fat physical and even for are considered at low risk on their BMI Moreover, similar are on to the of our This study was by the Ministry of Health and Welfare, Seoul, from and and from the US of