n-6 and n-3 polyunsaturated fatty acids （PUFAs） are essential nutrients for normal　brain development and function. Linoleic acid （LA） and α-linolenic acid （ALA） are the popular n-6 and n-3 PUFAs found in diet, and arachidonic acid （ARA） and docosahexaenoic acid （DHA） are the principal n-6 and n-3 PUFAs in the brain, respectively. ARA and DHA are rapidly deposited during brain development and are important regulators for embryonic neural stem cells. ARA and DHA share many enzymes in synthesis from the precursors, membrane phospholipid remodeling, and metabolism into lipid mediators, resulting in that ARA and DHA in the brain are generally competitive in these metabolic steps, and the dietary balance of n-6/n-3 PUFAs is considered to be important. However, intake of several vegetable oils, which are abundant in n-6 PUFAs, and that of fishes, which are abundant in n-3 PUFAs, have been increased and decreased, respectively, in many countries. I have recently reported that pregnant mice that consume a diet high in LA and low in ALA impairs neocortical development in the offspring by promoting the neurogenic-to-gliogenic fate transition of neural stem cells and also induces hedonic feeding behaviors in the offspring by upregulating midbrain dopaminergic system. In the present review, I summarize the functions of dietary n-6 and n-3 PUFAs in brain development.

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Lipids and fatty acids are crucial nutrients for growth and development during entire childhood from infants to adolescents, although high cholesterol and triglyceride levels are risk factors for cardiovascular diseases developed in adulthood. The concept of developmental origin of health and disease （DOHaD） is well established, and undernutrition in utero following a mismatch between pre- and postnatal environments permanently changes the body composition, function and metabolism that lead to atherosclerosis and metabolic syndrome in later life. Our investigations and research were carried out mainly in clinical and public health settings, focusing on subcutaneous adipose tissue development during infancy and its relating metabolic and hormonal factors. Based on our clinical data and clinical experiences, we reviewed here the relationship between intrauterine undernutrition and serum lipid/lipoprotein/fatty acid profile, subcutaneous adipose tissue development in light for gestational date （LFD） infants, children with metabolic syndrome born LFD, and the fluctuation of LDL-C levels observed in children/adolescents with heterozygous familial hypercholesterolemia. We would like to provide some implications for future studies regarding lipids/fatty acids metabolism and adipose tissue development during fetal and neonatal periods, which may link to metabolic syndrome and atherosclerosis in later life.

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Preterm birth occurs in 5% of all pregnancies in Japan, giving a life-long adverse impact on the baby. The regulation of inflammation balance in the uteroplacental system is a key to successful pregnancy. Deterioration of inflammatory regulation in the pregnant uterus is a major factor related to preterm birth. Inflammatory eicosanoids such as prostaglandin （PG）F2α and PGE2, are produced by the omega-6 fatty acid metabolic pathway and play an essential role in the progress of parturition controlling cervical ripening and uterine contraction. In contrast, accumulating evidence have suggested that the metabolic pathway of omega-3 fatty acids is closely involved in pregnancy maintenance with its anti-inflammatory functions physiologically against omega-6-derived substances. Past studies have implied that enhanced intake of omega-3 fatty acid in pregnant women reduces the incidence of preterm birth. Supporting those clinical findings, we previously found that fat-1 transgenic mice which have an omega-3 fatty acid-dominant internal environment were resistant to inflammation induced preterm birth. In the background mechanism, we confirmed that omega-3 fatty acid metabolites such as resolvin and 18-HEPE suppressed uterine inflammation. In this review article, the importance of omega-3 fatty acids in the control of uterine inflammation is discussed from a wide range of perspectives from basic researches to clinical intervention in pregnant women.

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Obese children suffer from a variety of complications. Among them, dyslipidemia is one of the most common complications. There are gender and age differences in serum TC and HDL-C levels in children. And as obesity becomes more severe, the lipid profile tends to be more atherosclerosis-inducing. Therefore, obesity treatment from childhood and correction of dyslipidemia associated with obesity are necessary for the primary prevention of cardiovascular disease. Since the diagnostic criteria for dyslipidemia differ between adults and children, it is necessary to use the diagnostic criteria for children. There are two types of dyslipidemia: primary dyslipidemia and secondary dyslipidemia, specifically, hyper-LDL-cholesterolemia, hypertriglyceridemia, and hypo-HDL-cholesterolemia. Familial hypercholesterolemia（ FH） is the most common cause of primary hyperlipidemia, but many cases of FH are not associated with obesity. On the other hand, secondary dyslipidemias that tend to be associated with obesity are hypertriglyceridemia and hypo-HDL-cholesterolemia. The treatment of these dyslipidemias is to correct excessive intake of simple sugars and carbohydrates, and to actively consume n-3 polyunsaturated fatty acids. For hypo-HDL-cholesterolemia, exercise is recommended in addition to dietary guidance.

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Feeding canola oil （Can） to stroke-prone spontaneously hypertensive rats （SHRSP） shortens their lifespan. This anomalous effect was also observed with partially hydrogenated oils the effectiveness of fully hydrogenated oil is still unclear. This study aimed to investigate the lifespan of SHRSP fed diets containing 10 %（w/w） of fully hydrogenated Can （FHCO） or other edible oils. For measuring survival, ｍale SHRSP were fed a test diet consisting of a mixture of rodent basal diet and one of the test oils in a 9:1 ratio. During the study period, food consumption of rats given FHCO was significantly increased（ 15–20% w/w） compared to the other oils. However, body weight gain in the FHCO group was suppressed and significantly less （10–12%） than that in control at 9–11 weeks of age. None of the rats in the FHCO group died until 180 days although other groups were died by around 130 days. Furthermore, after feeding test diets to other SHRSP for 7 or 12 weeks, blood pressure, serum lipid level, and histological analysis in brain and kidney were measured. FHCO remarkably decreased the serum cholesterol level both 7 and 12 weeks feeding and suppressed elevation of the systolic blood pressure from 12 weeks old. In addition, while some rats exhibited cerebral hemorrhage and renal dysfunction in the Can group at 16 weeks of age, no symptoms were observed in the FHCO group. This study suggested that complete hydrogenation decreases the toxicity of Can and even prolongs the lifespan in SHRSP.

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Childhood obesity is a growing public health issue in Japan, Europe, and the United States. Additionally, cases of pediatric type 2 diabetes resulting from obesity continue to increase. Thus, diabetes is no longer considered as an adult disease. The annual incidence of pediatric type 2 diabetes is 2.62 people per 100,000 with 83.7% suffering from obesity. In many cases of type 2 diabetes, the patient is obese owing to genetic and environmental factors. Type 2 diabetes develops with accumulation of visceral fat accompanied by increased insulin resistance and reduced insulin secretion. The age of onset peaks between 12 and 14 years, which corresponds with adolescence. This is a period during which the secretion of growth and sex hormones increases and insulin resistance becomes physiologically higher. It is necessary to control blood glucose levels early in such cases. If metabolic abnormalities, such as hyperglycemia persist, over time complications particular to diabetes, including retinopathy, nephropathy and neuropathy, occur. Additionally, the dyslipidemia that accompanies hyperglycemia promotes nonalcoholic fatty liver disease and arteriosclerosis, which cause conditions such as cirrhosis of the liver, myocardial infarction, and stroke. Most patients with pediatric type 2 diabetes are obese. Hence, the basic treatment strategy is diet and exercise therapy. However, diet and exercise therapy alone only effect blood glucose control in approximately 60% of patients, with the remainder requiring pharmacotherapy.

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