Fructose intake during gestation and lactation differentially affects the expression of hippocampal neurosteroidogenic enzymes in rat offspring

<p>Neurosteroids, steroidal hormones synthesized <i>de novo</i> from cholesterol within the brain, stimulate hippocampal functions such as neuron protection and synapse formation. Previously, we examined the effect of maternal fructose on the transcriptional regulation of neurosteroidogenic enzymes. We found that the mRNA expression level of the steroidogenic acute regulatory protein (StAR), peripheral benzodiazepine receptor (PBR), cytochrome P450(11β), 11β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD was altered. However, we could not determine whether maternal fructose intake played a role in the gestation or lactation period because the dam rats were fed fructose solution during both periods. Thus, in this study, we analyzed the hippocampi of the offspring of dams fed fructose during the gestation or lactation period. Maternal fructose consumption during either the gestation or lactation period did not affect the mRNA levels of StAR, P450(17α), 11β-HSD-2, and 17β-HSD-1. PBR expression was down-regulated, even when rats consumed fructose during the lactation period only, while fructose consumption during gestation tended to activate the expression of P450(11β)-2. We found that maternal fructose intake during gestation and lactation differentially affected the expression of hippocampal neurosteroidogenic enzymes in the offspring.</p

Correlation with dROMs levels.

<p>Correlation with dROMs levels.</p

Correlation with Log hsCRP levels.

<p>Correlation with Log hsCRP levels.</p

Correlation with Log Fstl1 levels.

<p>Correlation with Log Fstl1 levels.</p

Correlation between plasma Fstl1 levels and clinical parameters.

<p>Correlation of plasma Log Fstl1 levels with Log fasting immune-reactive insulin (FIRI), Log high sensitive CRP (hsCRP) and derivatives of reactive oxidative metabolites (dROMs) was analyzed.</p

Association between the Extent of Peripheral Blood DNA Methylation of <i>HIF3A</i> and Accumulation of Adiposity in community-dwelling Women: The Yakumo Study

DNA methylation in the CpG sites of intron 1 of HIF3A is associated with body mass index (BMI). This cross-sectional study investigated correlations between DNA methylation of HIF3A and BMI or adiposity parameters in the Japanese population. DNA methylation of HIF3A was quantified via pyrosequencing. DNA methylation of HIF3A differed only in women; DNA methylation level at cg27146050 was associated with visceral adipose tissue thickness and correlated with BMI and percent (%) body fat after excluding smokers. Peripheral blood DNA methylation at the CpG site (cg27146050) of HIF3A correlated with VAT thickness in Japanese women.</p

Clinical characteristics of all subjects.

<p>Clinical characteristics of all subjects.</p

Overexpression of KLF15 rescues the reduction of adipolin expression caused by TNFα.

<p>Quantitative RT-PCR method was used for measurement of mRNA levels. <b>A</b>, Adipolin mRNA levels treated with adenovirus expressing KLF9 (Ad-KLF9), KLF15 (Ad-KLF15) or β-galactosidase (Ad-β-gal) at 150 moi for 24 h in 3T3-L1 adipocytes. 3T3-L1 adipocytes were treated with TNFα (10 ng/ml) or vehicle for 24 h. N = 3 in each group. <b>B</b>, Adiponectin mRNA levels treated with Ad-KLF15 or Ad-β-gal at 150 moi for 24 h in 3T3-L1 adipocytes. 3T3-L1 adipocytes were treated with TNFα (10 ng/ml) or vehicle for 24 h. N = 3 in each group.</p

Expression of KLF15 augments the promoter activity of adipolin.

<p><b>A and B</b>, Effect of KLF15 and KLF9 on the promoter activity of adipolin. Protein levels of KLF15 (A) and KLF9 (B) in HEK293 cells transfected with pShuttle vector expressing KLF15 tagged with FLAG, KLF9 tagged with FLAG or empty vector (MOCK). Expression of KLF15 and KLF9 was evaluated by Western blot analyses using anti-FLAG antibody. HEK293 cells were transfected with pShuttle vector expressing KLF15, KLF9 or MOCK, along with pGL3-basic vectors containing adipolin promoter region (−66/−1 or −111/−1) or empty pGL3 vector in the presence of pRL-SV40. Promoter activity was assessed by luciferase reporter assay. Results are normalized relative to the values of empty pShuttle vectors (MOCK). N = 6 in each group. <b>C</b>, Luciferase assay for determination of adipolin promoter activity in 3T3-L1 adipocytes. 3T3-L1 adipocytes were transfected with pGL3-basic vectors containing adipolin promoter (−66/−1 or −111/−1) or empty pGL3 vector in the presence of pRL-SV40. N = 6 in each group.</p

Ablation of KLF15 by siRNA reduces adipolin expression in adipocytes.

<p>KLF15, adipolin (APL) and adiponectin (APN) mRNA levels were determined by quantitative RT-PCR method. <b>A</b>, KLF15 mRNA levels in 3T3-L1 adipocytes at 48 h after transfection with siRNA targeting KLF15 (si-KLF15) (20 nM) or non-targeting control siRNA (si-Control) (20 nM). N = 3 in each group. <b>B</b>, mRNA levels of APL and APN in 3T3-L1 adipocytes transfected with si-KLF15 (20 nM) or si-Control (20 nM). N = 3 in each group.</p