Lipid-binding, -transfer or -exchange proteins arepresent in intra- and extracellular fluids of all orgnisms. They play a role in the transport or targeting of lipids in the cell or in the plasma, but may also interact directly or indirectly by modulation of various cellular processes. The structure of these families of lipid-binding proteins, albumin, lipocalin and fatty acid-binding protein (FABP) families, has been established. FABP have similar molecular masses (14-15kDa) and amino acid compositions, exhibit some sequences similarity (38-70%), and form a family with other hydrophobic ligandbinding proteins such as celluar retinol-binding protein (CRBP), cellular retinoic acid-binding protein (CRABP) and intestinal bile acid-binding protein (I-BABP/I-15P/ILBP). At least, 7 types of FABP, liver (L), intestine (I), heart (H), brain (B), myelin (mP2), adipocyte (aP2) or skin type (E/C) FABP, have been isolated from various sources. The large similarity of H-HABP, aP2, mP2 and E/C-FABP (60-70%) is reflected in the similar amino acids on essential positions for fatty acid binding. Interestingly, these FABPs and CRBP I and II contain a protein tyrosine kinase recognition sequence before Tyr 19. The physiological relevance of tyrosine phosphorylation of FABP remains unclear. Furthermore, recently, a significant degree of primary sequence similarity was noted between a domain of an ion channel, the Nmethyl-D-aspartate receptor and the members of the FABP family, while the significance of FABP-like domain for ion channel regulation remains unknown.
X-ray diffraction analysis of FABP family proteins revealed that they show a structure of two short α-heliceslocated near N terminus and fbllowed by 10 anti-parallel β-strands. The β-strands are organized into two nearly orthogonal β-sheets giving the protein the overall appearance of a “clam shell”. To date, the genes for nine members of the FABP family have been identified. The overall organization of the genes is identical, four exons and three introns. The exon/intron boundaries are similar in all genes but the length of the intron sequences varies markedly.
Although FABP has been thought to be involved in the intracellular transport and metabolism of long-chain fatty acids or other hydrophorbic ligands, their physiological roles in cells are not precisely understood. Intracellular fatty acids are important molecules for energy delivery and for synthesis of membrane lipid mediators such as eicosanoids. Apart from their functioning as metabolic substrates and constituents of complex lipids, long-chain fatty acids are being recognized as elements of several cell-to-cell signal transduction pathways. Therefore, it would be interesting to examine mechanisms of the action of FABP involved in these cellular signal transduction.

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We examined height, body mass index (BMI), blood pressure, serum lipids (total cholesterol, HDL-cholesterol and triglyceride) and physical activity among 1, 558 children in the first, fourth and seventh grade between 1991 and 1995. In 1994, we also studied the serum fasting insulin levels. The mean levels of total cholesterol (TC), HDL-cholesterol (HDL-C), and triglyceride (TG) were significantly lower in the seventh grade children than in those in the fourth grade. Serum TC and HDL-C levels were positively correlated while HDL-C and TG levels were negatively correlated in all grades examined. Fasting serum insulin levels (IRI) were significantly hiher in the older children, and were generally higher in girls than in boys. IRI was positively correlated with BMI in the fourth and the seventh grade children;IRI was also positively correlated with TC and TG, but negatively correlated with HDL-C and physical activity in the seventh grade children. We further studied the relationship of serum lipids in subjects with TG levels higher than 60mg/dl (high TG group) and subjects with TG levels lower, than 60mg/dl (low TG group). In the first and the fourth grade children, TC and HDL-cholesterol levels showed a significant possitive regession in both groups. However the seventh grade boys in the high TG group did not show a significant regression of TC and HDL-C. Moreover, IRI levels were higher in the high TG group than in the low TG group.
Our findings suggest that the elevation of IRI and TG levels in older children may destroy the positive correlation between TC and HDL-C: thus, we conclude that IRI may serve as a useful indicator of metabolism of serum lipids in children.

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Objective:We studied the relationship between glucose and lipid metabolism abnormalities, to clarify the reduced insulin sensitivity and hypersinsulinemia in patients with arteriosclerosis associated with essential hypertension.
Method:In 25 patients with essential hypertension and normal glucose tolerance and in eight normal individuals with no family history of hypertension or diabetes mellitus, we measured the insulin sensitivity in peripheral tissue by oral glucose tolerance testing and the euglycemic glucose clamp method using an artifical pancreas. Since the glucose infusion rate in the normal individuals was 8.27±0.95mg/kg/min, 6.37mg/kg/min (-2SD), or higher level were regarded as normal insulin sensitivity, and a lower level as reduced insulin sensitivity. The relationship between the glucose tolerance test, and glucose, serum triglyceride, serum total cholesterol, serum HDL-cholesterol, and urinary noradrenaline, were studied.
Results:The glucose infusion rate was reduced in 64% of the patients with essential hypertension, who also showed an excessively delayed insulin secretion in the oral glucose tolerance test, and high accumulation of insulin (p<0.01), at 91.2±32.6μu/ml·hr. Lipid metabolism dosorders were found in 52% patients with essntial hypertension, and hypertriglyceridemia was seen in 44% of these patients. Serum triglyceride in patients with essential hypertension asociated with reduced insulin sensitivity showed a negative correlation with the glucose infusion rate (r=-0.77, p<0.01), and a positive correlation with the accumulated amount of insulin (r=-0.62, p<0.05). Hypercholesterolemia was found in 32% of the patients with essential hypertension, and total cholesterol showed a negative correlation with the glucose infusion rate (r=-0.51, p<0.05). Hyper LDLcholesterolemia was observed in 32% of the patients with essential hypertension, and LDL-cholesterol showed a negative correlation with the glucose infusion rate (r=-0.49, p<0.05). Hypo HDL-cholesterolemia was found in 36% of the patients with essential hypertension, and HDL-cholesterol showed a positive correlation with the glucose infusion rate (r=-0.54, p<0.05).
Conclusion:Reduced insulin sensitivity is often associated with essential hypertension, but a relationship between increased blood pressure and reduced insulin sensitivity can be ruled out. The reduced insluin sensitivity in related with glucose and insulin metablolism abnormalities and lipid metabolism abnormalities, mainly increases in serum triglyceride. In the prevention of the onset of arteriosclerosis as a fatal complication of essential hypertension, we recommend examination of insulin resistance by the euglycemic glucose clamp method using an artificial pancreas.

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Cilostazol is an anti-thrombotic and vasodilating agent, reported to have both anti-thrombotic and cerebral vasodilating effects. We investigated the effects of cilostazol on serum lipid concentrations and plasma fatty acid composition in diabetic patients with peripheral vessel diseases (PVD). The serum concentrations of total cholesterol (T-chol), triglycerides (TG), HDLcholesterol (HDL-C), Lp(a), remnant-like particlecholesterol (RLP-C) and plasma fatty acid composition were measured in 17 diabetic patients with PVD before and 1, 3, and 6 months after administration of cilostazol (200mg/day). Serum TG concentrations were significantly decreased after the administration. Plasma docosahexaenoic acids (DHA) levels were significantly increased after the administration. Other parameters showed no significant changes. Our findings suggested that cilostazol produced anti-atherosclerotic effects by decreasing TG and increasing DHA.

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A reduction of calcium (Ca) intake leads to Ca and magnesium (Mg) mobilization from the bone pool, and to Ca deposition in the soft tissues, especially in the central nervous system (CNS). It has been reported that 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane hydrochloride) participates in activating the cerebral metabolism and in maintaining an adequate Mg level in the CNS and other soft tissues, as well as Ca and Mg levels in the bones. Our previous research also indicated its involvement in metal metabolism in the tissues of rats fed low-Ca diets. In general, bifemelane hydrochloride tends to decrease Ca deposition in the CNS and soft tissues of rats fed low-Ca diets, thereby aiding in the prevention of atherosclerosis.
This study investigated the action of bifemelane hydrochloride on the preventive effects of bifemelane hydrochloride on magnesium and aluminum deposition in CNS tissues and bones of aged rats maintained on unbalanced mineral diets. Twenty-seven male, 18-month-old Wistar rats were maintained for 90 days on the following diets: (A) standard diet, (B) low-Ca-Mg+Al diet, (C) standard diet+forced oral administration of 10 mg bifemelane/kg/day, (D) low-Ca-Mg+Al diet+forced oral administration of 10mg bifemelane/kg/day. After ninety days, samples of frontal cortex and lumbar spine tissues were removed. Ca and Al contents of these tissues were measured by neutron activation analysis (NAA).
Neither the A-B groups nor the C-D groups showed a change in the Ca content of the lumbar spine. However, Ca concentration in frontal cortex of the B group significantly increased over that of the A and C groups. On the other hand, Al concentration in both the frontal cortex and lumbar spine in the A-C-D groups was significantly less than that of the B group.
Since bifemelane hydrochloride participates in activating the cerebral metabolism and in maintaining an adequate Mg level in the CNS and soft tissues by maintaining Ca and Mg levels in the bones, it is likely that bifemelane hydrochloride improves motor activity due to bone mineralization in aged rats fed low-Ca diets.

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Lipoprotein (a) (Lp(a)) is considered one of the potent independent risk factors for ischemic heart disease. Serum Lp(a) concentration is determined mainly by genetic factors, but environment factors can also affect the serum Lp(a) concentration. We investigated the effects of gender, age and menopause on surum Lp(a) concentration. In subjects undergoing health examinations at Keio Health Counseling Center (male 2382, female 1316:premenopausal group 429, menopausal group 794), serum Lp(a) concentration was determined by latex immunoassay(LIA). The mean value± standard deviation and median of serum Lp(a) concentration for males were 20.7±16.6, 16.1mg/dl and those for females were 25.7±20.5, 20.2mg/dl (premenopausal female: 21.8±18.2, 16.5mg/dl, menopausal female: 27.9±21.5, 22.8mg/dl), respectively. There was a significant difference between males and females after age-agjustment using ANOCOVA. The increase in serum Lp(a) concentration with age was significant. During the perimenopausal period, serum Lp(a) concentration gradually increased in females. Serum Lp(a) concentration in menopausal females was significantly higher than those in premenopausal females after ageadjustment using ANOCOVA.

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