Yohei Kitamura

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.

High levels of saturated very long-chain fatty acid (hexacosanoic acid; C26:0) in whole blood are associated with metabolic syndrome in Japanese men

OBJECTIVE Hexacosanoic acid (C26:0) is a saturated very long-chain fatty acid and high levels of C26:0 in red blood cells are reported to be closely related with risk factors of atherosclerosis. However, the relationship between absolute levels of C26:0 in whole blood and metabolic syndrome (MS) has not been determined. MATERIALS AND METHOD We divided 218 consecutive apparently healthy male subjects into an MS group (n=78) and a non-MS group (n=140) according to the definition of the International Diabetes Federation. The levels of C26:0 in whole blood were measured by gas liquid chromatography-mass spectrometry. RESULTS The MS group had significantly higher levels of C26:0 than the non-MS group (2.42+/-0.31mug/ml vs. 2.25+/-0.29mug/ml, P=0001). There was a significant association between the levels of C26:0 and the number of factors of MS. The levels of C26:0 positively correlated with age, blood pressure, triglyceride and fasting plasma glucose. Multivariate analysis revealed that the level of C26:0 is still an independent variable for the presence of MS after adjustment for age and each criterion of MS. CONCLUSION The absolute levels of C26:0 in whole blood appear to be associated with MS independent of its component parts.

High levels of very long-chain saturated fatty acid in erythrocytes correlates with atherogenic lipoprotein profiles in subjects with metabolic syndrome

AIM Very long chain saturated fatty acid (VLCFA) levels in erythrocytes are associated with metabolic syndrome (MS). However, the relationship between levels of the VLCFA ligonoceric acid (C24:0) in erythrocytes and the atherogenic lipoprotein profiles and inflammatory state in MS remain unclear. METHODS Based on the International Diabetes Federation (IDF) definition of MS, 195 apparently healthy males were assigned to either an MS group (n=38) or a non-MS group (n=157). Fatty acid composition of erythrocytes was determined by gas liquid chromatography. RESULTS Erythrocytes from the MS group had a significantly higher level of C24:0 than cells from the non-MS group (4.06±0.48% versus 3.88±0.34%; p=0.03). C24:0 levels were significantly correlated with several components of MS. The C24:0 levels showed a significant negative correlation with LDL and HDL particle size. Multivariate linear regression analysis showed that C24:0 levels were independently correlated with LDL particle size after adjusting for age and each MS criterion. C24:0 levels were also positively correlated with log-transformed high-sensitivity CRP levels (p=0.04). CONCLUSION C24:0 levels in erythrocytes are associated with specific atherogenic lipoprotein profiles and inflammation status in subjects with MS.

Enhanced production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in very long chain saturated fatty acid-accumulated macrophages

BackgroundDeterioration of peroxisomal β-oxidation activity causes an accumulation of very long chain saturated fatty acids (VLCSFA) in various organs. We have recently reported that the levels of VLCSFA in the plasma and/or membranes of blood cells were significantly higher in patients with metabolic syndrome and in patients with coronary artery disease than the controls. The aim of the present study is to investigate the effect of VLCSFA accumulation on inflammatory and oxidative responses in VLCSFA-accumulated macrophages derived from X-linked adrenoleukodystrophy (X-ALD) protein (ALDP)-deficient mice.ResultsElevated levels of VLCSFA were confirmed in macrophages from ALDP-deficient mice. The levels of nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ), intracellular reactive oxygen species (ROS), and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interluekin-6 (IL-6), and interleukin-12p70 (IL-12p70), were significantly higher in macrophages from ALDP-deficient mice than in those from wild-type mice. The inducible NO synthase (iNOS) mRNA expression also showed an increase in macrophages from ALDP-deficient mice.ConclusionThese results suggested that VLCSFA accumulation in macrophages may contribute to the pathogenesis of inflammatory diseases through the enhancement of inflammatory and oxidative responses.

High hexacosanoic acid levels are associated with coronary artery disease

AIMS Levels of saturated very long chain fatty acids (VLCFAs) are associated with coronary risk factors, including metabolic syndrome (MS), atherogenic lipoproteins, and systemic inflammation. However, the relationship between circulating levels of saturated VLCFA and coronary artery disease (CAD) remains unclear. METHOD We enrolled 100 consecutive CAD patients and 40 age-, gender-, and body mass index (BMI)-matched healthy control subjects. The levels of hexacosanoic acid (C26:0), a VLCFA, in whole blood were measured by gas-liquid chromatography mass spectrometry. RESULTS C26:0 levels were significantly higher in the CAD group than in the control group (2.42±0.32 vs. 2.27±0.24 μg/ml, P=0.01) and positively correlated with BMI (r=0.23, P=0.008), triglyceride levels (r=0.22, P=0.01), and hypertension (P=0.01). CAD patients with MS showed the highest C26:0 levels adjusted by hematocrit. Furthermore, adjusted C26:0 levels in CAD patients without MS were higher than those in controls (P=0.02), suggesting that C26:0 levels increased with the presence of CAD independent of MS. Our multivariate analysis revealed that high C26:0 levels in whole blood is an independent marker for CAD even after adjustment for age, gender, BMI, lipid profiles, fasting plasma glucose, and blood pressure. CONCLUSION High C26:0 levels in whole blood may be an independent marker for identifying the risks of CAD.

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.

Effect of dietary Lorenzo's oil and docosahexaenoic acid treatment for Zellweger syndrome

ABSTRACT  We investigated the possible therapeutic effect of decreasing plasma levels of very‐long‐chain fatty acids (C26:0) with a synthetic oil containing trioleate and trielucate (Lorenzos oil) as well as increasing docosahexaenoic acid (DHA) in red blood cells (RBC) with DHA ethyl ester in four patients with Zellweger syndrome. We investigated serial changes of plasma C26:0 levels and DHA levels in RBC membranes by gas‐liquid chromatography/mass spectrometry (GC/MS). After death, the fatty acid composition of each patients cerebrum and liver was studied. Dietary administration of Lorenzos oil diminished plasma C26:0 levels. Earlier administration of Lorenzos oil was more effective and the response did not depend on the duration of administration. DHA was incorporated into RBC membrane lipids when administrated orally, and its level increased for several months. The final DHA level was correlated with the duration of administration and was not related to the timing of initiation of treatment. DHA levels in the brains and livers of treated patients were higher than in untreated patients. Early initiation of Lorenzos oil and the long‐term administration of DHA may be useful for patients with Zellweger syndrome.

Effect of hypoxic-ischemic injury on serine palmitoyltransferase activity in the developing rat brain.

Background: Sphingolipid metabolism is strongly associated with central nervous system myelination. Ceramide is the most active of the sphingolipid metabolites. On the basis of ceramide biosynthesis indicated by serine palmitoyltransferase activity and cerebroside generated by ceramide, the evaluation of serine palmitoyltransferase activity in developing brains or hypoxic-ischemic damaged brains is worthwhile. Methods: Using a scintillation counter, we assessed serine palmitoyltransferase activity, a rate-limiting enzyme of sphingolipid metabolism, in the brains of developing rats and compared the activity with hypoxic-ischemic brains, using the method of Rice on postnatal day 7 (P7). Results: In the control groups, serine palmitoyltransferase activity was detected in the microsomal fraction of whole brain homogenates from P4, which was earlier than the initial expression of myelin-specific proteins such as myelin basic protein and proteolipid protein on immunochemistry. Serine palmitoyltransferase activity increased along with development on P8, P10, P14 and P21. However, hypoxic-ischemic brains showed lower serine palmitoyltransferase activity than control brains on P8, P10, P14 and P21. Conclusions: These results suggest that increase in serine palmitoyltransferase activity before myelin-specific protein expression may be an initial step in myelinogenesis and a decline in serine palmitoyltransferase activity in hypoxic-ischemic brains may be one of the major causes of delayed myelination.

Relationship between Changes in Fatty Acid Composition of the Erythrocyte Membranes and Fatty Acid Intake during Pregnancy in Pregnant Japanese Women

Objective: Docosahexaenoic acid (DHA) is an important nutrient required by pregnant women and fetuses. Several studies suggest that fatty acid composition changes during pregnancy. However, the association of longitudinal changes in erythrocyte fatty acid composition and dietary fatty acid intake during pregnancy is not well understood. We assessed the relationship between fatty acid composition of the erythrocyte membranes and fatty acid intake at each trimester in pregnant Japanese women. Methods: We conducted a prospective hospital-based cohort study. We investigated fatty acid composition of the erythrocyte membranes and intake of fatty acids during the three trimesters in 178 healthy, pregnant Japanese women. Results: The eicosapentaenoic acid and arachidonic acid percentage of the erythrocyte membranes significantly decreased. The percentages of linoleic acid and α-linolenic acid significantly increased during pregnancy. The DHA percentage in the erythrocyte membranes decreased from the second to the third trimester. The DHA percentage in the erythrocyte membranes positively correlated with DHA intake in the third trimester. Conclusion: In pregnant Japanese women, the fatty acid composition of the erythrocyte membranes markedly changed throughout pregnancy. The DHA intake in the third trimester may be insufficient to maintain DHA percentage in the maternal erythrocyte membranes.

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.