Association between Brain-Derived Neurotrophic Factor (BDNF) Levels in 2nd Trimester Amniotic Fluid and Fetal Development.

The development of the fetal nervous system mirrors general fetal development, comprising a combination of genetic resources and effects of the intrauterine environment. Our aim was to assess the 2nd trimester amniotic fluid levels of brain-derived neurotrophic factor (BDNF) and to investigate its association with fetal growth. In accordance with our study design, samples of amniotic fluid were collected from women who had undergone amniocentesis early in the 2nd trimester. All pregnancies were followed up until delivery and fetal growth patterns and birth weights were recorded, following which pregnancies were divided into three groups based on fetal weight: (1) AGA (appropriate for gestational age), (2) SGA (small for gestational age), and (3) LGA (large for gestational age). We focused on these three groups representing a reflection of the intrauterine growth spectrum. Our results revealed the presence of notably higher BDNF levels in the amniotic fluid of impaired growth fetuses by comparison with those of normal growth. Both SGA and macrosomic fetuses are characterized by notably higher amniotic fluid levels of BDNF (mean values of 36,300 pg/ml and 35,700 pg/ml, respectively) compared to normal-growth fetuses (mean value of 32,700 pg/ml). Though apparently small, this difference is, nevertheless, statistically significant (p value < 0.05) in SGA fetuses in the extremes of the distribution, i.e., below the 3rd centile. In conclusion, there is clear evidence that severe impairment of fetal growth induces the increased production of fetal brain growth factor as an adaptive mechanism in reaction to a hostile intrauterine environment, thereby accelerating fetal brain development and maturation

Metabolic phenotype of male obesity-related secondary hypogonadism pre-replacementand post-replacement therapy with intra-muscular testosterone undecanoate therapy

Aim: To explore the metabolic phenotype of obesity-related Secondary Hypogonadism (SH) in men pre- and post-replacement therapy with long-acting intramuscular (IM) testosterone undecanoate (TU). Methods: A prospective observational pilot study on metabolic effects of TU IM in male obesity-related SH (Hypogonadal [HG] group, n=13), including baseline comparisons with controls (Eugonadal [EG] group, n=15). Half the subjects (n=7 in each group) had Type 2 Diabetes Mellitus (T2D). Baseline metabolic assessment on Human Metabolism Research Unit: fasting blood samples; BodPod (body composition), and; whole-body indirect calorimetry. The HG group was treated with TU IM therapy for 6-29 months (mean 14.8-months [SD 8.7]), and assessment at the Human Metabolism Research Unit repeated. T-test comparisons were performed between baseline and follow-up data (HG group), and between baseline data (HG and EG groups). Data reported as mean (SD). Results: Overall, TU IM therapy resulted in a statistically significant improvement in HbA1C (9mmol/mol, P=0.03), with 52% improvement in HOMA%B. Improvement in glycaemic control was driven by the HG subgroup with T2D, with 18mmol/mol [P=0.02] improvement in HbA1C. Following TU IM therapy, there was a statistically significant reduction in fat mass (3.5Kg, P=0.03) and increase in lean body mass (2.9Kg, P=0.03). Lipid profiles and energy expenditure were unchanged following TU IM therapy. Comparisons between baseline data for HG and EG groups were equivalent apart from differences in testosterone, SHBG and BMR. Conclusion: In men with obesity-related SH (including a subgroup with T2D), TU IM therapy improved glycaemic control, beta cell function and body composition

Investigation of Testosterone, Androstenone, and Estradiol Metabolism in HepG2 Cells and Primary Culture Pig Hepatocytes and Their Effects on 17βHSD7 Gene Expression

Steroid metabolism is important in various species. The accumulation of androgen metabolite, androstenone, in pig adipose tissue is negatively associated with pork flavor, odour and makes the meat unfit for human consumption. The 17β-hydroxysteroid dehydrogenase type 7 (17βHSD7) expressed abundantly in porcine liver, and it was previously suggested to be associated with androstenone levels. Understanding the enzymes and metabolic pathways responsible for androstenone as well as other steroids metabolism is important for improving the meat quality. At the same time, metabolism of steroids is known to be species- and tissue-specific. Therefore it is important to investigate between-species variations in the hepatic steroid metabolism and to elucidate the role of 17βHSD7 in this process. Here we used an effective methodological approach, liquid chromatography coupled with mass spectrometry, to investigate species-specific metabolism of androstenone, testosterone and beta-estradiol in HepG2 cell line, and pig cultured hepatocytes. Species- and concentration-depended effect of steroids on 17βHSD7 gene expression was also investigated. It was demonstrated that the investigated steroids can regulate the 17βHSD7 gene expression in HepG2 and primary cultured porcine hepatocytes in a concentration-dependent and species-dependent pattern. Investigation of steroid metabolites demonstrated that androstenone formed a 3′-hydroxy compound 3β-hydroxy-5α-androst-16-ene. Testosterone was metabolized to 4-androstene-3,17-dione. Estrone was found as the metabolite for β-estradiol. Inhibition study with 17βHSD inhibitor apigenin showed that apigenin didn't affect androstenone metabolism. Apigenin at high concentration (50 μM) tends to inhibit testosterone metabolism but this inhibition effect was negligible. Beta-estradiol metabolism was notably inhibited with apigenin at high concentration. The study also established that the level of testosterone and β-estradiol metabolites was markedly increased after co-incubation with high concentration of apigenin. This study established that 17βHSD7 is not the key enzyme responsible for androstenone and testosterone metabolism in porcine liver cells. © 2012 Chen et al

Enhanced microbial bile acid deconjugation and impaired ileal uptake in pregnancy repress intestinal regulation of bile acid synthesis

Pregnancy is associated with progressive hypercholanemia, hypercholesterolemia, and hypertriglyceridemia, which can result in metabolic disease in susceptible women. Gut signals modify hepatic homeostatic pathways, linking intestinal content to metabolic activity. We sought to identify whether enteric endocrine signals contribute to raised serum bile acids observed in human and murine pregnancies, by measuring fibroblast growth factor (FGF) 19/15 protein and mRNA levels, and 7α-hydroxy-4-cholesten-3-one. Terminal ileal farnesoid X receptor (FXR)-mediated gene expression and apical sodium bile acid transporter (ASBT) protein concentration were measured by qPCR and western blotting. Shotgun whole-genome sequencing and ultra-performance liquid chromatography tandem mass spectrometry were used to determine the cecal microbiome and metabonome. Targeted and untargeted pathway analyses were performed to predict the systemic effects of the altered metagenome and metabolite profiles. Dietary CA supplementation was used to determine whether the observed alterations could be overcome by intestinal bile acids functioning as FXR agonists. Human and murine pregnancy were associated with reduced intestinal FXR signaling, with lower FGF19/15 and resultant increased hepatic bile acid synthesis. Terminal ileal ASBT protein was reduced in murine pregnancy. Cecal bile acid conjugation was reduced in pregnancy because of elevated bile salt hydrolase-producing Bacteroidetes. CA supplementation induced intestinal FXR signaling, which was not abrogated by pregnancy, with strikingly similar changes to the microbiota and metabonome as identified in pregnancy. Conclusion: The altered intestinal microbiota of pregnancy enhance bile acid deconjugation, reducing ileal bile acid uptake and lowering FXR induction in enterocytes. This exacerbates the effects mediated by reduced bile acid uptake transporters in pregnancy. Thus, in pregnant women and mice, there is reduced FGF19/15-mediated hepatic repression of hepatic bile acid synthesis, resulting in hypercholanemia

Absence of disparities in anthropometric measures among Chilean indigenous and non-indigenous newborns

<p>Abstract</p> <p>Background</p> <p>Studies throughout North America and Europe have documented adverse perinatal outcomes for racial/ethnic minorities. Nonetheless, the contrast in newborn characteristics between indigenous and non-indigenous populations in Latin America has been poorly characterized. This is due to many challenges, including a lack of vital registration information on ethnicity. The objective of this study was to analyze trends in anthropometric measures at birth in Chilean indigenous (Mapuche) and non-indigenous children over a 5-year period.</p> <p>Methods</p> <p>We examined weight and length at birth using information available through a national data base of all birth records for the years 2000 through 2004 (n = 1,166.513). Newborns were classified ethnically according to the origins of the parents' last names.</p> <p>Result</p> <p>The average birthweight was stable over the 5 year period with variations of less than 20 g in each group, and with mean values trivially higher in indigenous newborns. The proportion weighing less than 2500 g at birth increased modestly from 5.2% to 5.6% in non-indigenous newborns whereas the indigenous births remained constant at 5.2%. In multiple regression analyses, adjusting flexibly for gestational age and maternal characteristics, the occurrence of an indigenous surname added only 14 g to an average infant's birthweight while holding other factors constant. Results for length at birth were similar, and adjusted time trend variation in both outcomes was trivially small after adjustment. Anthropometric indexes at birth in Chile are quite favorable by international standards.</p> <p>Conclusion</p> <p>There is only a trivial degree of ethnic disparity in these values, in contrast to conditions for ethnic minorities in other countries. Moreover, these values remained roughly constant over the 5 years of observation in this study.</p

Worksite health screening programs for predicting the development of Metabolic Syndrome in middle-aged employees: a five-year follow-up study

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) management programs conventionally focus on the adults having MetS. However, risk assessment for MetS development is also important for many adults potentially at risk but do not yet fulfill MetS criteria at screening. Therefore, we conducted this follow-up study to explore whether initial screening records can be efficiently applied on the prediction of the MetS occurrence in healthy middle-aged employees.</p> <p>Methods</p> <p>Utilizing health examination data, a five-year follow-up observational study was conducted for 1384 middle-aged Taiwanese employees not fulfilling MetS criteria. Data analyzed included: gender, age, MetS components, uric acid, insulin, liver enzymes, sonographic fatty liver, hepatovirus infections and lifestyle factors. Multivariate logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence interval (CI) of risk for MetS development. The synergistic index (SI) values and their confidence intervals of risk factor combinations were calculated; and were used to estimate the interacting effects of coupling MetS components on MetS development.</p> <p>Results</p> <p>Within five years, 13% (175 out of 1384) participants fulfilled MetS criteria. The ORs for MetS development among adults initially having one or two MetS components were 2.8 and 7.3, respectively (both p < 0.01), versus the adults having zero MetS component count at screening. Central obesity carried an OR of 7.5 (p < 0.01), which far exceeded other risk factors (all ORs < 2.7). Synergistic effects on MetS development existed between coupling MetS components: 1. High blood pressure plus low-HDL demonstrated an OR of 11.7 (p < 0.01) for MetS development and an SI of 4.7 (95% CI, 2.1-10.9). 2. High blood pressure plus hyperglycemia had an OR of 7.9 (p < 0.01), and an SI of 2.7 (95% CI, 1.2-6.4).</p> <p>Conclusion</p> <p>MetS component count and combination can be used in predicting MetS development for participants potentially at risk. Worksite MetS screening programs simultaneously allow for finding out cases and for assessing risk of MetS development.</p

Maternal Undernutrition and Long-term Effects on Hepatic Function

Undernutrition in utero, regardless of the source, can impair proper liver development leading to long-term metabolic dysfunction. Understanding the molecular mechanisms underlying how nutritional deficits during perinatal life lead to permanent alterations in hepatic gene expression will provide better therapeutic strategies to alleviate the undernourished liver in postnatal life. This chapter addresses the different experimental models of undernutrition in utero, and highlights the direct and indirect mechanisms involved leading to metabolic diseases in the liver. These include hypoxia, oxidative stress, epigenetic alterations, and endoplasmic reticulum (ER) stress. In addition, promising perinatal nutritional and pharmaceutical interventions are highlighted which illustrate how the placidity of the developing liver can be exploited to prevent the onset of long-term metabolic disease

Weight and metabolic effects of cpap in obstructive sleep apnea patients with obesity

<p>Abstract</p> <p>Background</p> <p>Obstructive sleep apnea (OSA) is associated with obesity, insulin resistance (IR) and diabetes. Continuous positive airway pressure (CPAP) rapidly mitigates OSA in obese subjects but its metabolic effects are not well-characterized. We postulated that CPAP will decrease IR, ghrelin and resistin and increase adiponectin levels in this setting.</p> <p>Methods</p> <p>In a pre- and post-treatment, within-subject design, insulin and appetite-regulating hormones were assayed in 20 obese subjects with OSA before and after 6 months of CPAP use. Primary outcome measures included glucose, insulin, and IR levels. Other measures included ghrelin, leptin, adiponectin and resistin levels. Body weight change were recorded and used to examine the relationship between glucose regulation and appetite-regulating hormones.</p> <p>Results</p> <p>CPAP effectively improved hypoxia. However, subjects had increased insulin and IR. Fasting ghrelin decreased significantly while leptin, adiponectin and resistin remained unchanged. Forty percent of patients gained weight significantly. Changes in body weight directly correlated with changes in insulin and IR. Ghrelin changes inversely correlated with changes in IR but did not change as a function of weight.</p> <p>Conclusions</p> <p>Weight change rather than elimination of hypoxia modulated alterations in IR in obese patients with OSA during the first six months of CPAP therapy.</p

Protein and folic acid content in the maternal diet determine lipid metabolism and response to high-fat feeding in rat progeny in an age-dependent manner

Maternal diet during gestation can exert a long-term effect on the progeny’s health by programming their developmental scheme and metabolism. The aim of this study is to analyze the influence of maternal diet on lipid metabolism in 10- and 16-week-old rats. Pregnant dams were fed one of four diets: a normal protein and normal folic acid diet (NP-NF), a protein-restricted and normal folic acid diet (PR-NF), a protein-restricted and folic-acid-supplemented diet (PR-FS), or a normal protein and folic-acid-supplemented diet (NP-FS). We also tested whether prenatal nutrition determines the reaction of an organism to a postweaning high-fat diet. Blood biochemistry and biometrical parameters were evaluated. The expression patterns of PPARα, PPARγ, and LXRα in the liver and adipose tissue were examined by real-time PCR. In the 10-week-old, rats folic acid supplementation of the maternal diet was associated with reduced circulating glucose and total cholesterol concentrations (P < 0.01 and P < 0.001, respectively). Neither prenatal diets nor postnatal feeding affected blood insulin concentrations. In the 16-week-old rats, body weight, abdominal fat mass and central adiposity were reduced in the progeny of the folic acid–supplemented dams (P < 0.01, P < 0.001 and P < 0.01, respectively). Maternal protein restriction had no effect on biometry or blood biochemical parameters. Folic acid supplementation of the maternal diet was associated with reduced expression of PPARα, PPARγ, and LXRα in the liver (P < 0.001). Reduced protein content in the maternal diet was associated with increased PPARα mRNA level in the liver (P < 0.001) and reduced LXRα in adipose tissue (P < 0.01). PPARα and PPARγ transcription in the liver, as well as LXRα transcription in adipose tissue, was also dependent on interaction effects between prenatal and postnatal diet compositions. PPARγ transcription in the liver was correlated with the abdominal fat mass, body weight, and calorie intake, while PPARγ transcription in adipose tissue was correlated with reduced body weight and calorie intake. Total serum cholesterol concentration was correlated with LXRα transcription in the liver. Folic acid supplementation of the maternal diet may have favorable effects for lipid metabolism in the progeny, but these effects are modified by the postnatal diet and age. Furthermore, the expression of LXRα, PPARα, and PPARγ in the liver and adipose tissue largely depends on the protein and folic acid content in the maternal diet during gestation. However, the altered transcription profile of these key regulators of lipid metabolism does not straightforwardly explain the observed phenotype

Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes

<p>Abstract</p> <p>Background</p> <p>Escalating trends of obesity and associated type 2 diabetes (T2D) has prompted an increase in the use of alternative and complementary functional foods. <it>Momordica charantia </it>or bitter melon (BM) that is traditionally used to treat diabetes and complications has been demonstrated to alleviate hyperglycemia as well as reduce adiposity in rodents. However, its effects on human adipocytes remain unknown. The objective of our study was to investigate the effects of BM juice (BMJ) on lipid accumulation and adipocyte differentiation transcription factors in primary human differentiating preadipocytes and adipocytes.</p> <p>Methods</p> <p>Commercially available cryopreserved primary human preadipocytes were treated with and without BMJ during and after differentiation. Cytotoxicity, lipid accumulation, and adipogenic genes mRNA expression was measured by commercial enzymatic assay kits and semi-quantitative RT-PCR (RT-PCR).</p> <p>Results</p> <p>Preadipocytes treated with varying concentrations of BMJ during differentiation demonstrated significant reduction in lipid content with a concomitant reduction in mRNA expression of adipocyte transcription factors such as, peroxisome proliferator-associated receptor γ (PPARγ) and sterol regulatory element-binding protein 1c (SREBP-1c) and adipocytokine, resistin. Similarly, adipocytes treated with BMJ for 48 h demonstrated reduced lipid content, perilipin mRNA expression, and increased lipolysis as measured by the release of glycerol.</p> <p>Conclusion</p> <p>Our data suggests that BMJ is a potent inhibitor of lipogenesis and stimulator of lipolysis activity in human adipocytes. BMJ may therefore prove to be an effective complementary or alternative therapy to reduce adipogenesis in humans.</p