Comparison between placental gene expression of 11ß-hydroxysteroid dehydrogenases and infantile growth at 10 months of age.

AIM: The local expression of two isoenzymes of 11ß-hydroxysteroid dehydrogenase, type 1 (11ßHSD-1) and type 2 (11ßHSD-2), regulates the access of glucocorticoid hormones to their target cells. Reports on the association between the placental expression of 11ßHSD and infantile growth are limited. The aim of the present study was to investigate if the placental gene expression of 11ßHSD affects infantile growth at 10 months of age. METHODS: Placentas and umbilical venous cord blood were obtained from 42 singleton cases of cesarean deliveries between 31 and 40 weeks of gestation at Hamamatsu University Hospital between March 2009 and June 2010. The gene expression of both 11ßHSD-1 and 11ßHSD-2 was measured by quantitative reverse transcription polymerase chain reaction. Adiponectin and leptin levels in umbilical cord blood were measured using enzyme-linked immunoassay. RESULTS: 11ßHSD-1 and 11ßHSD-2 gene expression in human placentas did not correlate with bodyweight or the ponderal index (PI) at 10 months of age, whereas the gene expression of 11ßHSD-1, but not 11ßHSD-2, correlated with birthweight as well as PI at birth. Adiponectin levels in umbilical cord blood significantly correlated with the placental gene expression of 11ßHSD-1 as well as bodyweight and PI at 10 months of age, although no direct correlation was observed between them. CONCLUSION: No direct correlation was observed between the placental gene expression of 11ßHSD and infantile growth at 10 months of age. However, the placental gene expression of 11ßHSD-1 may be indirectly connected with infantile growth via adiponectin-associated metabolic regulation represented by adiponectin levels in umbilical cord blood.

Changes of maternal dietary intake, bodyweight and fetal growth throughout pregnancy in pregnant Japanese women.

AIM: The associations among changes in dietary intake, maternal bodyweight, and fetal growth during the course of pregnancy were investigated in a prospective cohort study carried out on 135 Japanese women. MATERIAL AND METHODS: Dietary intake was analyzed using digital photos of meals taken over 3 consecutive days, in the first, second and third trimester, and was compared with maternal bodyweight, estimated fetal bodyweight by ultrasound examination, and birthweight. RESULTS: Surprisingly, the mean total calorie intake remained below 1600 kcal/day during pregnancy, much lower than the value recommended in the 2010 edition of 'Dietary Reference Intakes for Japanese'. Dietary intake was similar throughout despite the recommendation of extra intake in late pregnancy. Maternal dietary intake did not correlate with fetal growth, although maternal bodyweight in the second trimester positively correlated with estimated fetal bodyweight in the third trimester. Maternal bodyweight before pregnancy positively correlated with birthweight. CONCLUSIONS: Maternal bodyweight as well as eating habits established before pregnancy may have a considerable effect on fetal growth. There is an urgent need to improve the diet of Japanese women of child-bearing age, especially during pregnancy.

Plasticity of histone modifications around Cidea and Cidec genes with secondary bile in the amelioration of developmentally-programmed hepatic steatosis.

We recently reported that a treatment with tauroursodeoxycholic acid (TUDCA), a secondary bile acid, improved developmentally-deteriorated hepatic steatosis in an undernourishment (UN, 40% caloric restriction) in utero mouse model after a postnatal high-fat diet (HFD). We performed a microarray analysis and focused on two genes (Cidea and Cidec) because they are enhancers of lipid droplet (LD) sizes in hepatocytes and showed the greatest up-regulation in expression by UN that were completely recovered by TUDCA, concomitant with parallel changes in LD sizes. TUDCA remodeled developmentally-induced histone modifications (dimethylation of H3K4, H3K27, or H3K36), but not DNA methylation, around the Cidea and Cidec genes in UN pups only. Changes in these histone modifications may contribute to the markedly down-regulated expression of Cidea and Cidec genes in UN pups, which was observed in the alleviation of hepatic fat deposition, even under HFD. These results provide an insight into the future of precision medicine for developmentally-programmed hepatic steatosis by targeting histone modifications.

Undernourishment in utero and hepatic steatosis in later life: A potential issue in Japanese people.

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. The prevalence of NAFLD in Japan has nearly doubled in the last 10-15 years. Increasing evidence supports undernourishment in utero being causatively connected with the risk of NAFLD in later life. Low body mass index (BMI) has been common among Japanese women of childbearing age for several decades due to their strong desire to be thin. It is plausible that insufficient maternal energy intake by pregnant Japanese women may underlie the rapid increase in the prevalence of NAFLD in Japan. In order to clarify the mechanisms by which undernourishment in utero primes adult hepatic steatosis, we developed a mouse model of fetal undernourishment with a hepatic fat deposit-prone phenotype on an obesogenic high fat diet in later life. We found that endoplasmic reticulum (ER) stress response parameters were activated concomitantly with the deterioration of hepatic steatosis and also that the alleviation of ER stress with the chemical chaperone, tauroursodeoxycholic acid (TUDCA), significantly improved hepatic steatosis. Therefore, undernourishment in utero may program the future integration of ER stress in the liver on an obesogenic diet in later life and also induce the deterioration of hepatic steatosis. These results also provide an insight into interventions for the potential high-risk population of NAFLD, such as those born small or exposed to maternal undernourishment during the fetal period, with the alleviation of ER stress by dietary supplements and/or specific food including chaperones.

Undernourishment in utero Primes Hepatic Steatosis in Adult Mice Offspring on an Obesogenic Diet; Involvement of Endoplasmic Reticulum Stress.

In order to investigate the possible involvement of endoplasmic reticulum (ER) stress in the developmental origins of hepatic steatosis associated with undernourishment in utero, we herein employed a fetal undernourishment mouse model by maternal caloric restriction in three cohorts; cohort 1) assessment of hepatic steatosis and the ER stress response at 9 weeks of age (wks) before a high fat diet (HFD), cohort 2) assessment of hepatic steatosis and the ER stress response on a HFD at 17 wks, cohort 3) assessment of hepatic steatosis and the ER stress response at 22 wks on a HFD after the alleviation of ER stress with a chemical chaperone, tauroursodeoxycholic acid (TUDCA), from 17 wks to 22 wks. Undernourishment in utero significantly deteriorated hepatic steatosis and led to the significant integration of the ER stress response on a HFD at 17 wks. The alleviation of ER stress by the TUDCA treatment significantly improved the parameters of hepatic steatosis in pups with undernourishment in utero, but not in those with normal nourishment in utero at 22 wks. These results suggest the pivotal involvement of the integration of ER stress in the developmental origins of hepatic steatosis in association with undernourishment in utero.