Subclass distribution of low-density lipoprotein triglyceride and the clustering of metabolic syndrome components in Japanese children.

BACKGROUND: Recent studies demonstrated that low-density lipoprotein-tryglyceride (LDL-TG) may represent another marker of cardiovascular risks. We therefore measured LDL-TG including the low-density lipoprotein (LDL) subclass distribution and investigated the association between LDL-TG subclass profile and the clustering of metabolic syndrome (MetS) components and insulin resistance in Japanese children. METHODS: The study included 237 schoolchildren (boys 115, girls 122). Four subclasses of low-density lipoprotein-tryglyceride (large, medium, small, and very small) was quantified using high-performance liquid chromatography. Total LDL-TG and TG levels in LDL subclasses were evaluated among four MetS component groups; non-abdominal obesity, abdominal obesity, pre-MetS, and MetS. RESULTS: Total LDL-TG (P = 0.0003, P = 0.0175) and triglyceride levels in LDL subclasses were significantly different among four MetS component groups (large: P = 0.0002, P = 0.0084; medium: P = 0.0009, P = 0.0491; small: P =0.0025, P = 0.0509; very small: P = 0.0808, P = 0.0228; boys and girls, respectively). Total LDL-TG (r = 0.411, P < 0.0001, r = 0.378. P < 0.0001) and triglyceride levels in LDL subclasses correlated positively with the homeostasis model of assessment ratio (large: r = 0.396, P < 0.0001, r = 0.346, P < 0.0001; medium: r = 0.274, P = 0.0030, r = 0.228, P = 0.0115; small: r = 0.342, P = 0.0002, r = 0.292, P = 0.0011; very small: r = 0.385, P < 0.0001, r = 0.426, P < 0.0001, boys and girls, respectively). CONCLUSIONS: Subclass distribution of LDL-TG was significantly associated with the clustering of MetS components in both sexes, and insulin resistance is a significant determinant of LDL-TG in all LDL subclasses. Lipoprotein-tryglyceride subclass analysis, rather than LDL-C, may provide a precise evaluation for cardiovascular disease risks in children with MetS.

Non-high-density Lipoprotein Cholesterol Levels in Japanese Obese Boys with Metabolic Syndrome.

AIM: To investigate the relationship between the clustering of metabolic syndrome (MetS) components and non-high-density lipoprotein cholesterol (non-HDL-C) levels in Japanese obese boys. METHODS: Subjects were 58 obese boys aged 12.0±2.6 years, which were categorized into three subgroups: abdominal obesity, pre-MetS (abdominal obesity＋1 component), and MetS (abdominal obesity＋2 or more components). RESULTS: Sixteen (27.6%) and 32 (55.2%) of the obese boys were diagnosed as pre-MetS and MetS, respectively. The mean non-HDL-C level in total subjects was 139.0±36.4 mg/dl and that in boys with abdominal obesity, pre-MetS, and MetS were 112.9±34.4, 135.4±37.9, and 149.0±32.6 mg/dl, respectively (p=0.0183, ANOVA). CONCLUSIONS: Japanese obese boys with MetS exhibited elevated non-HDL-C levels, suggesting that they may have a higher risk for the development of atherosclerotic diseases.

Effect of cod liver oil supplementation on the stearoyl-CoA desaturase index in obese children: a pilot study.

To investigate the effects of n-3 polyunsaturated fatty acids on stearoyl-CoA desaturase (SCD) activity, we treated 10 obese children (mean age: 12.9 years) with cod liver oil once daily for 12 weeks. The effects of cod liver oil supplementation on SCD activity, as estimated by the palmitoleate/palmitate ratio, depended on the docosahexaenoic acid (DHA) contents at baseline. Baseline DHA contents were negatively correlated with baseline SCD activity. After the treatment, baseline DHA contents were found to be significantly associated with the reduction of SCD activity. Cod liver oil supplementation may be a complementary treatment for obese children with low baseline contents of DHA.

Relationship between estimated fatty acid desaturase activities and abdominal adiposity in Japanese children.

BACKGROUND: Abdominal obesity alters the composition of plasma and tissue long chain fatty acids and thus affects a number of important physiological functions relating to the development of cardiometabolic diseases. The fatty acid composition is modulated by desaturases; stearoyl-CoA desaturase (SCD), delta-6 desaturase (D6D) and delta-5 desaturase (D5D). Therefore, we examined the relationship between the desaturase activities and abdominal adiposity. METHODS: One hundred eighty-one children (98 males, 83 females), including 42 children with abdominal obesity having waist to height ratio (WHtR) >0.5, were recruited. Fatty acid composition in plasma phospholipids was analyzed by gas chromatography after overnight fast, and SCD activity was estimated by 18:1/18:0 ratio. RESULTS: In children without abdominal obesity, WHtR correlated positively with D6D activity (r = 0.252, p = 0.0027) and negatively with SCD activity (r = −0.289, p = 0.0006), but not with D5D activity (r = −0.159, p = 0.0607). While in children with abdominal obesity, WHtR had a positive association with SCD activity (r = 0.332, p = 0.0315), but not with D6D (r = 0.267, p = 0.0847) or D5D activity (r = 0.008, p = 0.9600). CONCLUSION: The relationship between the desaturase activities and abdominal adiposity altered in children with abdominal obesity. Especially, SCD activity demonstrated a U-shaped association with WHtR.

Apolipoprotein A-V level may contribute to the development of obesity-associated dyslipidemia.

AIM: In a mice study, insulin suppressed apolipoprotein A-V (apoA-V) gene expression in a dose dependent manner. Thus, we investigated the association between apoA-V levels and dyslipidemias in obese children with hyperinsulinemia. METHODS: The subjects were 17 obese children (15 male, 2 female) aged 11.8 ± 2.4 years. Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), triglyceride (TG), apoA-V and insulin levels were determined. RESULTS: Obese children with hyperinsulinemia had greater percent overweight, higher TG level, lower HDLC level and lower apoA-V level than those without hyperinsulinemia. In simple regression analysis, apoA-V level correlated negatively with TG (r = -0.613, p = 0.0152) and insulin levels (r = -0.566, p = 0.0279), and positively correlated with HDLC (r = 0.811, p = 0.0002). In stepwise regression analysis, insulin level emerged as the independent determinant of TG level after apoA-V level was taken into account, whereas apoA-V emerged as the independent determinant of HDLC level after adjusting for insulin level. CONCLUSIONS: Insulin may be a potent regulator of serum apoA-V level in obesity, and apoA-V level may partly contribute to the development of obesity-associated dyslipidemia.

Abdominal adiposity is associated with fatty acid desaturase activity in boys: implications for C-reactive protein and insulin resistance.

Fatty acid composition, which is altered in patients with abdominal obesity, is influenced not only by dietary intake but also by the desaturating enzymes stearoyl-CoA desaturase (SCD), delta-6 desaturase (D6D) and delta-5 desaturase (D5D). We investigated desaturase activities and their associations with metabolic risk factors, C-reactive protein levels (CRP) and insulin resistance in Japanese children. There were 237 school children in this study; 115 were boys. The fatty acid composition of plasma phospholipids was analyzed, and the following desaturase activities were estimated: SCD (16:1n-7/16:0 and 18:1n-9/18:0), D6D (20:3n-6/18:2n-6) and D5D (20:4n-6/20:3n-6). D6D and D5D activities, but not SCD activity, were significantly associated with triglyceride levels, high-density lipoprotein cholesterol levels and insulin resistance in both sexes, and with CRP levels in boys. In addition, increased abdominal adiposity was significantly associated with increased D6D activity, and decreased D5D activity and insulin resistance in both sexes, and with increased CRP levels in boys. The n-6 polyunsaturated fatty acid desaturation pathway may be associated with metabolic risk factors, insulin resistance and increased inflammation in children with abdominal obesity, especially in boys.

Association of changes in body fatness and fatty acid composition of plasma phospholipids during early puberty in Japanese children.

AIMS: Plasma fatty acid composition can change with age, reflecting diet and levels of desaturating enzymes such as stearoyl-CoA desaturase (SCD), delta-6 desaturase (D6D) and delta-5 desaturase (D5D), which contribute to the development of insulin resistance. This study analyzed longitudinal changes in fatty acid composition in Japanese children during early puberty and the association between changes in desaturase indices and changes in body fatness and insulin resistance. METHODS: The study included 77 children (38 boys and 39 girls) aged 9.6±0.5 years. Relative weight (RW) and waist-to-height ratio (WHtR) were determined. The fatty acid composition of plasma phospholipids was analyzed by gas chromatography, and the desaturase indices were calculated: SCD (16:1n-7/16:0: SCD16 and 18:1n-9/18:0: SCD18), D6D (20:3n-6/18:2n-6) and D5D (20:4n-6/20:3n-6) in 2006 and 2009. RESULTS: Obese children showed higher dihomo-gamma linolenic acid (DGLA; 20:3n-6), a higher D6D index and lower D5D index than non-obese children. Longitudinal changes in fatty acid com-position were generally similar in both sexes. Increased D6D index and DGLA and decreased D5D index were significantly associated with increased WHtR in boys and girls. In addition, increased D6D index was associated with an increased homeostasis model of assessment ratio (HOMA-R) only in girls. CONCLUSION: The change in abdominal adiposity is a determinant of longitudinal changes in D6D and D5D indices and DGLA during early puberty.

Docosahexaenoic acid content in plasma phospholipids and desaturase indices in obese children.

AIMS: In obesity, fatty acid composition is altered with reduced docosahexaenoic acid (DHA) levels. Desaturating enzymes, stearoyl-CoA desaturase (SCD), delta-6 desaturase (D6D) and delta-5 desaturase (D5D) modulate fatty acid composition and are thus associated with the development of metabolic syndrome. The aim of this study was to identify the relationships among DHA content, desaturase indices and the components of metabolic syndrome in childhood obesity. METHODS: Thirty-two obese children (27 male, 5 female) aged 12.0±2.6 years (mean±SD), with a relative body weight greater than 120% of the standard weight for sex, age and height, were recruited. Fatty acid composition of plasma phospholipids was analyzed by gas chromatography, and the desaturase indices were assessed: SCD (16:1n-7/16:0 and 18:1n-9/18:0), D6D (20:3n-6/18:2n-6) and D5D (20:4n-6/20:3n-6). RESULTS: No sex difference was observed in fatty acid composition. DHA content tended to have an inverse association with body mass index (BMI) (r=-0.337, p=0.0592), and correlated significantly with very low-density lipoprotein-triglyceride (r=-0.558, p=0.0057). In addition, DHA content had significant negative relationships with SCD indices (SCD16; r=-0.373, p=0.0357 and SCD18; r=-0.580, p=0.0005), which correlated positively with BMI(r=0.439, p=0.0120, r=0.353, p=0.0473, respectively), but had no association with D5D or D6D. CONCLUSIONS: DHA content in obese children was independent of the desaturation of alpha-linolenic acid. Reduced DHA content was associated with increased SCD index, and might contribute to the development of metabolic syndrome. Dietary management including fatty acids is suggested to be important to prevent and better manage obesity.

Apolipoprotein A-V is a potent modulator of HDL and VLDL components in preadolescent children.

AIM: Mice lacking apolipoprotein A-V (apoA-V) displayed an increase in serum triglyceride (TG) levels; however, the correlation of apoA-V levels with TG levels in humans is controversial, and the exact mechanism by which apoA-V affects TG levels is unclear. The aim of the present study was to clarify the impact of apoA-V on the lipoprotein subclass profile in preadolescent children, which has not been studied. METHOD: The study subjects were 178 (89 male, 89 female) 4th grade elementary school children (mean+/-SD: 9.5+/-0.5 years old). ApoA-V levels were determined by an enzyme-linked immunosorbent assay, and the lipid component of each lipoprotein fraction and their particle sizes were measured by HPLC. RESULTS: Levels of apoA-V showed no gender difference in preadolescent children, and were not affected by anthropometric variables. ApoA-V had a negative association with serum TG levels and TG levels in each lipoprotein fraction, and a positive association with HDL-C. In particular, apoA-V appears to contribute to the increase in cholesterol levels in the larger HDL fraction. CONCLUSIONS: It was suggested that apoA-V is a potent modulator of HDL and VLDL components in preadolescent children.

Concentrations of very long-chain fatty acid in whole blood are associated with cardiovascular risk factors in children.

BACKGROUND: Fatty acid metabolism has a close relationship with metabolic syndrome. Saturated very long-chain fatty acid (hexacosanoic acid; C26:0) was recently reported to be associated with cardiovascular risk factors in adults. METHODS: Eighty-eight children (47 male, 41 female; average age, 10.9 y) participated in this study. Concentrations of C26:0 in whole blood were measured. RESULTS: Compared with reported concentrations in the whole blood of adults, children had lower C26:0 concentrations, which had a close relationship with abdominal obesity, increased concentrations of low-density lipoprotein cholesterol and high blood pressure. C26:0 concentrations increased with increasing number of risk factors. CONCLUSIONS: Elevation of C26:0 concentrations may be one of the metabolic features of children with cardiovascular risk factors.

Characteristics of obese children with low content of arachidonic acid in plasma lipids.

BACKGROUND: Although there have been many studies on the relationship between obesity and long-chain polyunsaturated fatty acid (LCPUFA), the results and their interpretation are controversial, especially in children. Arachidonic acid (AA), the product of n-6 LCPUFA, is reported to be related to insulin resistance. The purpose of the present paper was to investigate the LCPUFA profile in obese children and mechanisms that contribute to reduced AA content. METHOD: An age- and sex-matched control study was performed. The study subjects were 59 obese children (mean age, 11.8 years) and 53 healthy non-obese children (mean age, 12.5 years). The study parameters included anthropometric measurements, serum lipids, leptin and fatty acid composition in plasma. RESULTS: Plasma fatty acids in obese children had lower linoleic acid (P < 0.0001) and higher dihomo-gamma-linolenic acid (P = 0.0004) than those in non-obese children. In all subjects combined, delta-6 desaturase (D6D) index (ratios of [C 18:3n-6+C 20:2n-6]/C 20:4n-6 or C 20:4n-6/C 18: 2n-6) correlated with leptin (P < 0.0001). There was no significant difference in AA content between obese and non-obese. However, the AA content was low (

Determination of lipid composition of plasma lipoproteins in children with a rapid agarose gel electrophoresis method.

The agarose gel electrophoresis and differential staining system is an easy and quick method for analyzing the serum lipid composition of each lipoprotein fraction. It has been reported in adults that measured values obtained by this method strongly correlated with those obtained by ultracentrifugation. The aim of this study was to examine the clinical application of this method for children, in comparison with the ultracentrifugation method. The subjects were sixteen hyperlipidemic and twenty-five normolipidemic children, aged from two to eighteen years old. Cholesterol (C) and triglyceride (TG) levels were determined in serum very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fractions by both methods. Correlation coefficients between the two methods for cholesterol levels were 0.937 (HDL), 0.983 (LDL) and 0.837 (VLDL), and for triglyceride levels were 0.735 (HDL), 0.621 (LDL) and 0.964 (VLDL). We confirmed the clinical application of this method to evaluate the lipoprotein lipid profile in children as well as in adults.

Thr-encoding allele homozygosity at codon 54 of FABP 2 gene may be associated with impaired delta 6 desatruase activity and reduced plasma arachidonic acid in obese children.

BACKGROUND: Alanine-for-threonine substitution at codon 54 (A54T polymorphism) in the fatty acid-binding protein 2 gene (FABP2) has been associated with hypertriglyceridemia and insulin resistance. Impairment in the activity of delta 6 and 5 desaturases is also supposed to be a factor predisposing the development of insulin resistance syndrome. AIM: We investigated the relationship between A54T polymorphism in FABP2 and the impairment of long-chain polyunsaturated fatty acid metabolism in obese children. METHODS: Thirty-two obese children participated. During the study, the children continued their habitual diet, which was documented in a 3-day food record using household measures. Anthropometry was performed, and serum lipid and fatty acid composition in plasma were analyzed. The polymorphism of codon 54 in the FABP 2 gene was analyzed. RESULTS: The allele frequency was 0.66 and 0.34 for Ala54 and Thr54, respectively. There were no significant differences in age, body mass index, fasting serum glucose, insulin or serum lipoproteins among the three polymorphism groups. These were also no significant differences in the intake of energy, the percentage of energy nutrients or in the dietary lipid composition. The content of arachidonic acid (AA) in plasma was lowest in Thr/Thr54 (p < 0.05). The indices of delta-6 desaturase (D6D) activity in Thr/Thr54 were significantly lower than in Thr/Ala54 or Ala/Ala54 (p < 0.05, p < 0.01, respectively). CONCLUSIONS: In obese children, Thr/Thr54 of the FABP 2 gene is associated with impaired activation of D6D and reduced AA content. The results in the LCPUFA profile suggest that Thr/Thr54 may predispose the to development of insulin resistance.

Relationship between serum adiponectin level and lipid composition in each lipoprotein fraction in adolescent children.

The association of lipid composition in each lipoprotein fraction with adiponectin level in relation to body fatness was investigated. The subjects were 283 children (144 boys and 139 girls) aged 11.6 years (S.D. 1.5). Cholesterol (C) and triglyceride (TG) levels in each lipoprotein fraction were measured by a combination of agarose gel electrophoresis and differential staining. Adiponectin level was not significantly different between girls and boys. In simple regression analyses, an association of adiponectin level with lipoprotein lipid profile was shown only in girls, and not in boys at all. In girls, very low-density lipoprotein (VLDL)-C, low-density lipoprotein (LDL)-C, VLDL-TG and LDL-TG were negatively correlated with adiponectin level, and high-density lipoprotein (HDL)-C and HDL-C/TG ratio were positively correlated. Multiple regression analyses including adiponectin level and body mass index (BMI) as predictors for the lipoprotein lipid profile demonstrated that adiponectin level was a significant independent predictor of VLDL-TG, LDL-C, LDL-TG, HDL-C and HDL-C/TG ratio. In conclusion, adiponectin level correlates with lipoprotein lipid profile independent of body fatness in adolescent girls.

Plasma palmitoleic acid content and obesity in children.

BACKGROUND: Palmitoleic acid (16:1n-7) is a product of endogenous lipogenesis. In human obesity, 16:1n-7 is reported to correlate with indexes of adiposity and insulin concentrations. OBJECTIVE: We investigated the relation between adiposity, especially in the abdominal region, and plasma monounsaturated fatty acid (MUFA) profiles in obese children. DESIGN: A case-control study was performed. The study subjects were 59 obese children (x +/- SD age: 11.8 +/- 3.8 y) and 53 age- and sex-matched healthy, nonobese children (aged 12.5 +/- 0.5 y). The study's variables included anthropometric measurements, serum lipids, leptin, and fatty acid composition in plasma. RESULTS: MUFA profiles of obese subjects showed a significantly higher content of 16:1n-7, 18:1n-9, and 20:1n-9 and significantly higher stearoyl-CoA desaturase (SCD) activity (ratio of 16:1n-7 to 16:0) than in nonobese controls. In a multiple regression analysis, percentage body fat, waist-to-height ratio, and waist-to-hip ratio (WHR) were significant determinants of 16:1n-7 content. SCD activity had a positive, significant correlation with leptin. However, in a multiple regression analysis that included percentage body fat, WHR, and leptin as independent determinants, WHR was the only determinant of SCD activity. CONCLUSIONS: Plasma 16:1n-7 content has a significant relation with abdominal adiposity in obese children. This change in the MUFA profile may be caused by activation of SCD that is not sufficiently suppressed by leptin. Endogenous lipogenesis may be an important factor in the pathogenesis of obesity in children.

Assessment of individual changes in body fatness in boys during early pubertal period.

BACKGROUND: In order to know whether the changes in indexes of overweight, body mass index (BMI; kg/m2) and percentage of overweight (POW) (%), really represent the tendency toward obesity, we examined longitudinal individual changes in these indexes, and the change in body composition in boys during early pubertal period. METHODS: The subjects were 50 school boys who lived in Shizuoka, Japan. Standing height and weight were measured, and BMI and POW were obtained. Body fat percentage (BF%), fat mass (FM) and lean body mass (LBM) were estimated by bioelectrical impedance method. The influence of predictive variables (LBM, FM) on the changes in BMI and POW was investigated by multiple regression analysis. We examined the 3-year changes in BMI, POW and predictive variables in each individual, from 9 to 12 years of age. RESULTS: The mean change of BMI was 1.7 +/- 0.3 (mean +/- SEM) kg/m2 and that of POW was 2.2 +/- 1.9%. The influence of predictive variables on the changes in BMI and POW was determined. The variance of the change in POW could be explained by that in FM (r(2) = 0.737, P < 0.0001), while the change in BMI was influenced by both LBM and FM (r2 = 0.891, P < 0.0001). CONCLUSIONS: Based on the definition of obesity, POW is the better index of body fatness to assess its individual change for boys during early pubertal period, because the index independent from the change in LBM is supposed to be the appropriate index for obesity in practical use.

Screening for familial combined hyperlipidemia in children using lipid phenotypes.

The purpose of this study was to screen for FCHL in children using serum lipid phenotypes. The subjects were 1190 (599 male, 591 female) children who participated in a screening and care program for life style-related diseases in school children. Total cholesterol, high-density lipoprotein cholesterol and triglyceride were determined, and information on the family history of parents was obtained by questionnaire. Candidates for FCHL were screened by the following criteria; type IIb hyperlipidemia, type IIa hyperlipidemia with positive family history of CHD, hyperlipidemia or both. We informed them of the results by mail. A second series of examinations to diagnose FCHL was performed on volunteer participants, including their parents. The candidates consisted of 9 children with type IIb and 27 with type IIa hyperlipidemia, 11 of whom participated, in the second series of examinations, in which 5 children were diagnosed with FCHL. The prevalence was 0.4%, suggesting that at least half of all individuals with FCHL already demonstrate hyperlipidemia in childhood.

Familial combined hyperlipidemia (FCHL) in children: the significance of early development of hyperapoB lipoproteinemia, obesity and aging.

It is not easy to make diagnose FCHL in children, since a clear expression of lipoprotein abnormality is unlikely and standard criteria have not yet been established. We investigated eight cases of childhood FCHL and their families with respect to familial history, anthropometric parameters and serum lipoprotein levels, to explore the characteristics of childhood FCHL. To diagnose childhood FCHL it is necessary to clarify both the family history and lipid profiles of the parents. In this study, two prominent features were suggested; that serum TG level is affected by both obesity and age, and also in particular, that a significantly elevated level of serum apoB is a predominant feature of FCHL in childhood. It was found that hyperapoB may be revealed antecedently without other lipid abnormalities at an early age. Regardless of other lipoprotein abnormality, it was suggested that hyperapoB might be added to the early diagnostic criteria for FCHL.