Platelet-Activating Factor Acetylhydrolase Concentration in Children With Abdominal Obesity
2006; Lippincott Williams & Wilkins; Volume: 26; Issue: 5 Linguagem: Inglês
10.1161/01.atv.0000217284.86123.2c
ISSN1524-4636
AutoresTomoo Okada, Michio Miyashita, Yuki Kuromori, Fujihiko Iwata, Kensuke Harada, Hiroaki Hattori,
Tópico(s)Adipokines, Inflammation, and Metabolic Diseases
ResumoHomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 26, No. 5Platelet-Activating Factor Acetylhydrolase Concentration in Children With Abdominal Obesity Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBPlatelet-Activating Factor Acetylhydrolase Concentration in Children With Abdominal Obesity Tomoo Okada, Michio Miyashita, Yuki Kuromori, Fujihiko Iwata and Kensuke Harada Hiroaki Hattori Tomoo OkadaTomoo Okada Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan Search for more papers by this author , Michio MiyashitaMichio Miyashita Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan Search for more papers by this author , Yuki KuromoriYuki Kuromori Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan Search for more papers by this author , Fujihiko IwataFujihiko Iwata Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan Search for more papers by this author and Kensuke HaradaKensuke Harada Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan Search for more papers by this author Hiroaki HattoriHiroaki Hattori Department of Advanced Medical Technology and Development, BMI, Inc, Saitama, Japan Search for more papers by this author Originally published1 May 2006https://doi.org/10.1161/01.ATV.0000217284.86123.2cArteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:e40–e41To the Editor:In human obesity, increased oxidant stress is an important factor in the development of atherosclerosis.1 Oxidation of the lipid components of low-density lipoprotein (LDL) is causative, because oxidized LDL contributes to many of the stages of progression of atherosclerosis. In particular, small dense LDL particle, which is frequently associated with abdominal obesity,2 is susceptible to oxidative modulation. Even in obese children, oxidative stress including oxidized LDL formation is increased.3,4Platelet activating factor acetylhydrolase (PAF-AH) is a Ca2+-independent phospholipase A2 that catalyzes the conversion of platelet activating factor (PAF) to lyso-PAF. Another physiological function of plasma PAF-AH is to degrade oxidized phospholipids, which are formed during the oxidative modification of lipoproteins. Therefore, PAF-AH may play a significant role in atherogenesis as an antioxidant. We measured PAF-AH concentration in children with abdominal obesity and investigated its relationship with anthropometric and metabolic parameters.The subjects were 17 obese children (10 male, 7 female) aged 11.9±0.7 years (mean±SE) who presented to our outpatient clinic with obesity. Obesity was defined as a relative body weight >120%, which was calculated according to the standard weight obtained for sex, age, and height on the basis of data from the Ministry of Education, Science, Sports, and Culture.5 Skinfolds were measured at triceps and subscapular regions using a skinfold caliper. Waist circumference was measured at the umbilical level. Blood samples were collected in the morning after a 12-hour fast. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and triglyceride (TG) levels were determined by standard enzymatic methods. LDL cholesterol (LDLC) was calculated by means of the Friedewald formula. LDL peak particle diameter was determined using gel electrophoresis according to our previous report.2 Apolipoprotein B (ApoB) concentration was measured by tubidimetric immunoassay. Plasma insulin and glucose concentrations were determined and homeostasis model of assessment ratio (HOMA-R) was obtained using Matthews formula as an index of insulin resistance.6 Plasma PAF-AH concentration was measured by ELISA.7 All children were free from disease except for hyperlipidemia and obesity. Informed consent was obtained from each child and the parents.The prevalence of hypercholesterolemia (>220 mg/dL), hypertriglyceridemia (>120 mg/dL), and low HDLC level ( 110 mg/dL). HOMA-R was 5.4±1.4. All children had abdominal obesity, which was defined as waist/height ratio over 0.5. PAF-AH concentration was 1.5±0.1 μg/mL, with no significant sex difference. In simple regression analyses, PAF-AH concentration correlated positively with relative weight (r2=0.272, P=0.0316), waist/height ratio (r2=0.296, P=0.0240), subscapular/triceps ratio (r2=0.312, P=0.0304), and LDLC level (r2=0.248, P=0.0421), but not with apoB level (r2=0.171, P=0.0988), HDLC level (r2=0.079, P=0.2738), peak LDL particle diameter (r2=0.192, P=0.0787), or HOMA-R (r2=0.018, P=0.6043). In stepwise regression analysis (Table), LDLC level and waist/height ratio emerged as significant and independent determinants explaining 68.8% of the PAF-AH concentration variability after relative weight and subscapular/triceps ratio were taken into account. Stepwise Multiple Regression Analysis for PAF-AH Concentration as the Dependent VariableIndependent VariableβSErThis model includes LDL cholesterol, waist/height ratio, relative weight, and subscapula/tricep ratio as independent variables. r2=0.688; P=0.009.LDLC0.0100.0030.614Waist/height ratio5.9232.0240.476%These results suggested that abdominal obesity in children might be associated with oxidative stress, with antioxidative modulation of lipoproteins.In adults with metabolic syndrome, total plasma PAF-AH activity was reported to be higher than in those without metabolic syndrome.8 Adults with non–insulin-dependent diabetes mellitus also have increased plasma PAF-AH activity, which is correlated with their LDLC level.9 In our study, plasma PAF-AH concentration was correlated with LDLC level and waist/height ratio. Waist circumference is a major component of metabolic syndrome. In children, however, waist/height ratio rather than waist circumference is a better predictor of cardiovascular risk, because their height increases with aging.10 Therefore, our results demonstrated that PAF-AH concentration, as well as a high LDLC level, is associated with abdominal adiposity in obese children.Tsimihodimos et al reported that LDL-associated PAF-AH activity is mainly distributed on the small dense LDL particles.11 In our study, however, PAF-AH concentration is not correlated with peak LDL particle diameter. In children with abdominal obesity, antioxidant modulation of lipoproteins may precede the development of the predominance of small dense LDL. In Japanese adults with hyperlipidemia, the distribution of PAF-AH between HDL and LDL was altered with higher concentration of HDL-associated PAF-AH and lower non-HDL associated PAF-AH to apoB ratio.6 In our study, PAF-AH to apoB ratio correlated negatively with HDLC level (r2=0.244, P=0.0437), not with LDLC level or peak LDL particle diameter. Therefore, not only plasma concentration of PAF-AH but also the distribution of PAF-AH should be investigated to determine the mechanisms contributing to atherogenicity in obese children.Plasma PAF-AH deficiency is associated with atherosclerotic occlusive disease in Japanese adults, suggesting a protective role of PAF-AH.12 In abdominal obese children, PAF-AH concentration was elevated with increasing degree of abdominal fatness. PAF-AH may play an important role as the antioxidative factor even in the early phase of atherosclerosis.1 Keaney JF, Larson MG, Vasan RS, Wilson PWF, Lipinska I, Corey D, Massaro JM, Sutherland P, Vita JA, Benjamin EJ. Obesity and systemic oxidant stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol. 2003; 23: 434–439.LinkGoogle Scholar2 Miyashita M, Okada T, Kuromori Y, Harada K. LDL particle size, fat distribution and insulin resistance in obese children. Eur J Clin Nutr. 2006; 60: 416–420.CrossrefMedlineGoogle Scholar3 Atabek ME, Vatansev H, Erkul I. Oxidative stress in childhood obesity. J Pediatr Endocrinol Metab. 2004; 17: 1063–1068.MedlineGoogle Scholar4 Mohn A, Catino M, Capanna R, Giannini C, Marcovecchio M, Chiarelli F. Increased oxidative stress in prepubertal severely obese children: effect of a dietary restriction-weight loss program. J Clin Endocrinol Metab. 2005; 90: 2653–2658.CrossrefMedlineGoogle Scholar5 Yamazaki K, Matsuoka H, Kawanobe S, Hujita Y, Murata M. Evaluation of standard body weight by sex, age and height—on the basis of 1990 school year data. J Jpn Ped Sci. 1994; 98: 96–102(in Japanese with English abstract).Google Scholar6 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 284: 12–19.Google Scholar7 Kujiraoka T, Iwasaki T, Ishihara M, Ito M, Nagano M, Kawaguchi A, Takahashi S, Ishi J, Tsuji M, Egashira T, Stepanova IP, Miller NE, Hattori H. Altered distribution of plasma PAF-AH between HDLs and other lipoproteins in hyperlipidemia and diabetes mellitus. J Lipid Res. 2003; 44: 2006–2014.CrossrefMedlineGoogle Scholar8 Rizos E, Tambaki AP, Gazi I, Tselepis AD, Elisaf M. Lipoprotein-associated PAF-acetylhydrolase activity in subjects with the metabolic syndrome. Prostaglandins Leukot Essent Fatty Acids. 2005; 72: 203–209.CrossrefMedlineGoogle Scholar9 Serban M, Tanaseanu C, Kosaka T, Vidulescu C, Stoian I, Marta DS, Tanaseanu S, Moldoveanu E. Significance of platelet-activating factor acetylhydrolase in patients with non-insulin-dependent (type 2) diabetes mellitus. J Cell Mol Med. 2002; 6: 643–647.CrossrefMedlineGoogle Scholar10 Hara M, Saitou E, Iwata F, Okada T, Harada K. Waist-to-height ratio is the best predictor of cardiovascular disease risk factors in Japanese schoolchildren. J Atheroscler Thromb. 2002; 9: 127–132.CrossrefMedlineGoogle Scholar11 Tsimihodimos V, Karabina SA, Tambaki AP, Bairaktari E, Goudevenos JA, Chapman MJ, Elisaf M, Tselepis AD. Atorvastatin preferentially reduces LDL-associated platelet-activating factor acetylhydrolase activity in dyslipidemias of type IIA and type IIB. Arterioscler Thromb Vasc Biol. 2002; 22: 306–311.CrossrefMedlineGoogle Scholar12 Unno N, Nakamura T, Kaneko H, Uchiyama T, Yamamoto N, Sugatini J, Miwa M, Nakamura S. Plasma platelet-activating factor acetylhydrolase deficiency is associated with atherosclerotic occlusive disease in Japan. J Vasc Surg. 2000; 32: 263–270.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Costa K, Lacerda D, Silveira A, Martins L, Oliveira M, Rezende B, Menezes-Garcia Z, Mügge F, Silva A, Teixeira M, Rouault C, Pinho V, Marcelin G, Clément K and Ferreira A (2021) PAF signaling plays a role in obesity-induced adipose tissue remodeling, International Journal of Obesity, 10.1038/s41366-021-00961-9, 46:1, (68-76), Online publication date: 1-Jan-2022. 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(2007) Current World Literature, Current Opinion in Endocrinology, Diabetes & Obesity, 10.1097/MED.0b013e3282c3a898, 14:4, (329-358), Online publication date: 1-Aug-2007. May 2006Vol 26, Issue 5 Advertisement Article InformationMetrics https://doi.org/10.1161/01.ATV.0000217284.86123.2cPMID: 16627814 Originally publishedMay 1, 2006 PDF download Advertisement
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