Cholesterol Uptake Capacity in Cord Blood of Preterm Infants.

BACKGROUND: There is insufficient research on cholesterol uptake capacity (CUC) in preterm infants; therefore, the relationship between CUC and cholesterol transport in preterm infants is unclear. This study aimed to clarify the relationship between CUC and anthropometric measurements, high-density lipoprotein cholesterol (HDL-C) levels, and HDL-C subclasses in preterm infants. METHODS: Fifty-eight preterm infants were divided into small-for-gestational age (n = 20) (SGA) and appropriate-for-gestational age (AGA) (n = 38). CUC was measured using a fully automated immunoassay system, HI-1000. HDL-C subclasses were measured using high-performance liquid chromatography. RESULTS: SGA showed significantly lower HDL-C and CUC levels than AGA. We found a positive correlation between CUC and birth weight, birth height, and birth head circumference in preterm infants. Moreover, CUC had a strong relationship with HDL-C and very large, large, and medium HDL-C in preterm infants. CONCLUSIONS: In preterm infants, CUC is associated with normal growth and may indicate the ability to transport cholesterol forward by large-or medium-size HDL.

Lipoprotein-subclass particle numbers in children with abdominal obesity.

BACKGROUND: The lipoprotein particle number (PN) profile may be a better marker of cardiovascular risks than standard serum lipid measurements. The aim of this study was to analyze the lipoprotein PNs in Japanese children with abdominal obesity and to determine the subclass profile. METHODS: The participants included 164 Japanese children (79 boys and 85 girls) aged 9-13 years. We obtained waist-to-height ratios (WHtR) and serum lipids for all participants. The lipoprotein PNs in 12 subclasses were analyzed using high performance liquid chromatography (HPLC). RESULTS: Both boys and girls with abdominal obesity (WHtR ≧ 0.5) had significantly higher triglyceride (TG), very-low-density lipoprotein (VLDL)-PN, and all VLDL-subclass PNs compared to those without abdominal obesity. In boys with abdominal obesity, low-density lipoprotein (LDL)-PN was higher, but lipoprotein cholesterol (LDL-C) was not, and high-density lipoprotein cholesterol (HDL-C) was lower, but HDL-PN was not compared to those without abdominal obesity. In girls with abdominal obesity, LDL-C and LDL-PN were not significantly different and both HDL-C and HDL-PN were lower compared to those without abdominal obesity. Subclass analyses demonstrated that boys and girls with abdominal obesity had significantly lower very large and large HDL-PNs than those without abdominal obesity. In addition, medium, small, and very small LDL-PNs were higher in boys with abdominal obesity than those without abdominal obesity. CONCLUSIONS: This study found that Japanese children with abdominal obesity are affected by the lipoprotein-subclass PN profile, with sex differences in the LDL- and HDL-subclasses, which is different from results obtained by standard serum lipid measurements.

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.

Umbilical cord blood stearoyl-CoA desaturase index and lipoprotein lipase mass level in small-for-gestational age newborns.

We previously reported that triglyceride (TG) levels in small-for-gestational age (SGA) newborns were significantly higher than those in appropriate-for-gestational age (AGA) newborns. Stearoyl-CoA desaturase (SCD) activity is required for TG synthesis, while lipoprotein lipase mass (LPLm) facilitates TG clearance. The purpose of this study is to reveal whether SCD activity or LPLm is the cause of high TG levels in SGA newborns. Fifty-five newborns were classified as AGA (n = 42) and SGA (n = 13). Serum LPLm, TG and fatty acids in umbilical cord blood were analyzed. Then, [16:1 (n-7)]/ [16:0] and [18:1 (n-9)]/ [18:0] were calculated as SCD16 and SCD18 activities, respectively. The SGA group showed significantly higher TG levels and significantly lower LPLm levels than the AGA group. However, SCD16 and 18 activities were lower in SGA newborns than in AGA newborns. In conclusion, LPLm, rather than SCD activity may be involved in the increased TG levels in SGA newborns.

The Characteristics Of Abdominal Fat Distribution In Japanese Adolescents With Type 2 Diabetes Mellitus.

PURPOSE: The aim was to investigate the characteristics of abdominal fat distribution in Japanese adolescents with type 2 diabetes mellitus. PATIENTS AND METHODS: Eighty-six Japanese adolescents with simple obesity or type 2 diabetes mellitus treated between 2002 and 2018 were included. The subjects were classified into the simple obesity group (SO group, n=38) and type 2 diabetes mellitus group (DM group, n=23) by matching average age and gender ratio. The metabolic parameters VFA, SFA, and V/S ratio were compared between the 2 groups. Multivariate logistic regression analysis was performed to identify clinical factors associated with type 2 diabetes mellitus. Linear regression analysis was performed between hemoglobin A1c (HbA1c) and visceral fat area (VFA), subcutaneous fat area (SFA), or VFA-to-SFA ratio (V/S ratio) among all enrolled subjects. Finally, correlation analyses were performed to determine the relationships between VFA, SFA, and V/S ratio and metabolic parameters of the DM group. For the metabolic parameters, serum lipids, alanine aminotransferase (ALT), and HbA1c were measured without fasting. The VFA and SFA at umbilical level were investigated using computed tomography. RESULTS: VFA and V/S ratio in DM group were higher than those in SO group (p=0.04 and p<0.01, respectively). SFA in DM group was lower than that in SO group (p<0.01). VFA and SFA, and non-high density lipoprotein (HDL) cholesterol were identified as being independently associated with type 2 diabetes mellitus (odds ratio, 1.05, 0.98, and 1.04, respectively, p<0.05). HbA1c was correlated with VFA and V/S ratio (p<0.01). In DM group, VFA and SFA were positively correlated with systolic blood pressure (p<0.01), ALT (p<0.05), total cholesterol (p<0.05), and non-HDL cholesterol (p<0.01); however, V/S ratio was not correlated. CONCLUSION: Abdominal fat distribution in Japanese adolescents with type 2 diabetes mellitus was different from those with simple obesity and might associate with glucose and lipid metabolism.

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.

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.

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.

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.

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.

Waist-to-height ratio is the best predictor of cardiovascular disease risk factors in Japanese schoolchildren.

In adults, visceral fat accumulation is an important indicator for cardiovascular disease risk. This relationship is not fully understood in children. To determine the best predictor of cardiovascular disease risk factors among anthropometric indices such as body mass index (BMI), percent body fat (%Fat), waist-to-hip ratio (WHR), waist circumference, and waist-to-height ratio (W/Ht ratio) in Japanese schoolchildren. This study included 880 children (447 boys and 433 girls), 9-13y of age. Dependent variables were total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), atherogenic index (AI), life style related disease prevention score, and systolic (SBP) and diastolic (DBP) blood pressure. The strongest correlation was found between W/Ht ratio and the score by Pearson's correlation analysis. Multiple regression analysis showed that significant independent correlates for the score included W/Ht ratio and %Fat. Among the anthropometric indices, W/Ht ratio was the most significant predictor for TC, TG, LDLC, AI, and the score. W/Ht ratio is the best predictor of cardiovascular risk factors in Japanese schoolchildren. We propose using W/Ht ratio for detecting cardiovascular disease risk in children.

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.

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.

Abdominal adiposity is associated with high-density lipoprotein subclasses in Japanese schoolchildren.

BACKGROUND: The large HDL subclass is considered to possess cardioprotective properties. The purpose of this study is to determine the relationship among abdominal adiposity, insulin resistance and HDL subclass profiles of Japanese schoolchildren. METHODS: The study subjects included 164 children (79 boys and 85 girls). We obtained waist to height ratio (WHtR), lipid profile, and HOMA-IR. The HDL subclass profile was analyzed by HPLC. RESULTS: Children of either sex with abdominal obesity (WHtR≥0.5) had reduced concentrations of very large, large, and medium HDLC in conjunction with elevated triglyceride (TG) concentrations and HOMA-IR. WHtR was inversely related to the concentrations of very large (boys: r=-0.5306, p<0.0001; girls: r=-0.3483, p=0.0011), large (r=-0.6168, p<0.0001; r=-0.4387, p<0.0001), and medium (r=-0.4170, p=0.0001; r=-0.4116, p<0.0001) HDLC. The multiple regression analyses revealed that WHtR was an independent factor of the concentrations of very large, large, small, and very small HDLC in boys and the concentrations of large and medium HDLC in girls. CONCLUSIONS: In Japanese schoolchildren, abdominal obesity is associated with atherogenic HDL subclass profile. Abdominal obesity may be an important target for the prevention and management of HDL subclass alteration, even in children who do not suffer from insulin resistance or hypertriglyceridemia.

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.