SummaryThe maternal nutritional status during pregnancy and lactation influences the risk of obesity in offspring, but the details of this phenomenon are unclear. In particular, there is little information on the influence on the offspring of the maternal nutritional status during lactation only. Therefore, in this study, we examined the influence of high dietary fat intake in dams during lactation on the risk of obesity in offspring, using C57BL/6J mice. The mice were fed a control diet (CD) during pregnancy. After birth, dams were fed a CD or a high-fat diet (HD) during lactation (3 wk). Fat and energy were significantly increased in milk from dams fed a HD during lactation. Male offspring were weaned at 3 wk old and fed a CD for 4 wk, which resulted in no significant difference in their physique. Four weeks after weaning, the offspring (7 wk old) were fed a CD or HD for 4 wk to induce obesity. High dietary fat intake in dams and offspring promoted lipid accumulation in white adipose tissue and adipocyte hypertrophy in male offspring. The underlying mechanism may involve an increase in expression of Lpl and a decrease in expression of Hsl in white adipose tissue of offspring. In conclusion, our results show that high dietary fat intake during lactation promotes development of diet-induced obesity in male offspring. Key Words lactation, high-fat diet, offspring, obesity, adipocyte hypertrophy E-mail: tsudukit@m.tohoku.ac.jp Abbreviations: Acc, acetyl-CoA carboxylase; C, offspring at weaning from dams fed CD during lactation; C-CD, dams fed CD during lactation and offspring fed CD; CD, control diet; Cd36, cluster of differentiation 36; C-HD, dams fed CD during lactation and offspring fed HD; Fas, fatty acid synthase; G6p-dh, glucose-6-phosphatate dehydrogenase; Gapdh, glyceraldehyde-3-phosphate dehydrogenase; Glut4, glucose transporter type 4; H, offspring at weaning from dams fed HD during lactation; HD, high-fat diet; H-CD, dams fed HD during lactation and offspring fed CD; H-HD, dams fed HD during lactation and offspring fed HD; Hsl, hormone sensitive lipase; Lpl, lipoprotein lipase; Me, malic enzyme; NEFA, non-esterified acid; PL, phospholipid; Pparg, peroxisome proliferator-activated receptor g; qRT-PCR, quantitative reverse transcriptase-PCR; SE, standard errors; Srebp-1c, sterol regulatory element binding protein-1c; TC, total cholesterol; TG, triacylglycerol.

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Since the Japanese are known for their long life span, Japanese food has potential for health promotion. To identify the era of Japanese food that was beneficial to health, we investigated the health enhancing effects of Japanese foods from different eras, focusing on lipid and carbohydrate metabolic systems. Based on the National Nutrition Survey, representative one-week menus of Japanese foods from 2005, 1990, 1975 and 1960 were prepared, cooked, and powderized. Each mixture of Japanese food was given to normal ICR mice and senescence-accelerated mice (SAM) P8 as a 30 % mixture in standard diet for eight months. As a result, the Japanese food mixture from 1975 suppressed lipid accumulation in white adipose tissues in both mouse strains. To examine the underlying mechanisms, we conducted DNA microarray analysis of the liver, which is responsible for energetic lipid metabolism. As a result, the Japanese food mixture from 1975 promoted gene expression for high-energy expenditure in ICR mice. Additionally, the Japanese food mixture from 1975 promoted gene expression for enhanced degradation of triglycerides, suppression of fatty acid synthesis, and cholesterol catabolism in SAMP8 mice. Overall, it was suggested that components of Japanese foods from around 1975 are more effective than those of modern Japanese foods in preventing metabolic syndrome.

Malnutrition due to aging is partly caused by decreased absorption of nutrients by the gastrointestinal tract. However, the underlying mechanism is unclear and changes in lipid absorption with aging are poorly understood. In this study, changes in lipid absorption with aging were examined in mice aged 3 and 25 months. After overnight fasting, blood samples were collected from snipped tails and then soybean oil was administered orally. Three hours later, mice were sacrificed by decapitation and the liver, pancreas, small intestine and blood were collected. The increase in serum triacylglycerol after soybean oil administration was significantly lower in the older mice, indicating a decrease in lipid absorption with aging. Measurement of mRNA levels for triacylglycerol absorption-related genes showed that mRNA for pancreatic lipase tended to decrease in 25-month-old mice. There was no significant difference in the protein level of pancreatic lipase, but the enzyme activity showed a significant decrease in the older mice. To examine this mechanism, expression levels of mRNA for protein turnover-related genes in the pancreas were measured. The level of a proteasomal mRNA showed a significant decrease in 25-month-old mice. This suggests that the ability to degrade unfolded protein decreases in the aging pancreas, and that this leads to reduction of pancreatic lipase activity and a decrease in lipid absorption.

In this study, to study the effect of aging and Apolipoprotein E (ApoE) deficiency on antioxidant ability in mice, we examined whether lipid peroxidation is promoted by aging in ApoE deficient (ApoE−/−) mice, which have a shorter lifespan than normal mice. The levels of thiobarbituric acid-reactive substances (TBARS), a biomarker of lipid peroxidation, were measured in plasma and liver in ApoE−/− mice aged 12 weeks (young) and 52 weeks (early stage of senescence). TBARS in plasma and liver were significantly increased by aging. Next, we examined the reasons why lipid peroxidation was promoted by aging, based on measurement of protein and mRNA levels for antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in liver in ApoE−/− mice aged 12 and 52 weeks. The levels of superoxide dismutase 1 and 2 in liver were significantly decreased by aging. The mRNA level of catalase was also significantly decreased and the mRNA levels of superoxide dismutase 1, superoxide dismutase 2 and glutathione peroxidase 1 all showed a tendency to decrease with age. These results suggest that lipid peroxidation is caused by reduction of antioxidant activity with aging and that this promotes senescence and shortens lifespan in ApoE−/− mice.