11beta-hydroxysteroid dehydrogenase 2 activity is elevated in severe obesity and negatively associated with insulin sensitivity

Alterations in glucocorticoid (GC) metabolism may contribute to the development of obesity and insulin resistance. We aimed to study the role of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in human adiposity, paying special attention to the association between altered GC metabolism and insulin sensitivity. In 24-h urine samples of 72 extremely obese (mean BMI 45.5 +/- 1.1 kg/m(2)), but otherwise healthy patients urinary free cortisol (UFF), urinary free cortisone (UFE), tetrahydrocortisol (THF), 5alpha-tetrahydrocortisol (5alpha-THF), and tetrahydrocortisone (THE) were quantified by radioimmunoassay. The sum of the three major tetrahydrometabolites is an estimate for daily GC secretion, and the sum of UFF and UFE represents potentially bioactive-free-GCs. Thirty healthy lean subjects (BMI 22.3 +/- 0.3 kg/m(2)) served as controls. In obese subjects, absolute daily GC secretion and the potentially bioactive-free-GCs were significantly (P < 0.005) higher than in lean controls (11.8 +/- 0.7 vs. 8.0 +/- 0.6 mg/d; and 171.8 +/- 11.2 vs. 117.6 +/- 9.2 mug/d, respectively). However, when these values were corrected for body surface area (BSA), significant differences were no longer detectable. While enzyme activity indices for 5alpha-reductase and 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) were similar in lean and obese subjects, 11beta-HSD2 was markedly elevated in adiposity (3.7 +/- 0.2 vs. 2.1 +/- 0.1; P < 0.0001). This increase was accompanied by a significant reduction in UFF excretion corrected for BSA (16.5 +/- 1.2 vs. 21.7 +/- 2.0 mug/d/m(2); P = 0.0222). Besides, 11beta-HSD2 activity was significantly correlated with insulin sensitivity (P = 0.0262). When body size is accounted for, both adrenal GC secretion and potentially bioactive-free-GCs are indistinguishable between lean and extremely obese subjects. However in obesity, the kidney appears to intensify its supply of the direct substrate cortisone for extrarenal 11beta-HSD1, which may fuel visceral adiposity and insulin resistance.     

Immunosuppressive activity associated with early pregnancy in the bovine

Immunosuppressive activity was assessed in uterine flushings (UF) and uterine vein serum and plasma from nonpregnant and early-pregnant cows, and in media from the short-term culture of Day 18 bovine embryos. The preparations were tested for their ability to inhibit [3H] thymidine (3H-TdR) incorporation into phytohemagglutinin-stimulated bovine lymphocytes. On Days 2-3 (called Day 3), Days 9-10 (called Day 10), and Days 17-19 (called Day 18) of the estrous cycle (estrus = Day 0) and pregnancy, untreated and superovulated cows were anesthesized and jugular vein and uterine vein blood was collected. The uteri were removed and flushed to obtain UF and embryos. Uterine flushings were concentrated and tested for immunosuppressive activity at 400 micrograms uterine protein/ml culture fluid. Uterine flushings from both Day 18 pregnant and Day 18 nonpregnant cows were immunosuppressive (8/8), whereas Day 10 UF were usually not immunosuppressive (7/10). Day 3 UF were usually stimulatory or only marginally suppressive (8/8). Uterine vein serum and plasma from Day 18 cows were not suppressive when compared to jugular vein serum or plasma from the same cow; neither were Day 18 uterine vein serum or plasma suppressive when compared to those same samples taken from Day 3 cows. Embryo culture media obtained from the 48-h culture of Day 18 embryos was consistently suppressive. The activity was lost after dialysis in 1000-Mr cut-off tubing, removed by charcoal, and reduced by protease digestion. These results suggest two mechanisms whereby the embryo could escape immune rejection: 1) the progesterone-induced secretion of a uterine immunosuppressive substance(s) and 2) the production by the embryo of a low molecular weight immunosuppressive substance(s).     

Emotional sensitivity for motherhood: Late pregnancy is associated with enhanced accuracy to encode emotional faces

Previous research suggests that female sex hormones can increase the sensitivity of women's emotion processing systems. The largest rises in sex hormone levels in a woman's life are from early to late pregnancy. The current study, therefore, investigated whether changes in emotion processing are seen across pregnancy. Hypervigilant emotion processing has been implicated in the aetiology of anxiety. Therefore enhanced emotion processing across pregnancy has implications for women's vulnerability to anxiety. Ability to encode facial expressions of emotion was assessed in 101 women during early pregnancy and again in 76 of these women during late pregnancy. Symptoms of anxiety were measured using a clinical interview (The CIS-R). Consistent with previous research, the presence of anxiety symptoms was associated with greater accuracy to encode faces signalling threat (fearful and angry faces). We found that women had higher accuracy scores to encode emotional expressions signalling threat or harm (fearful, angry and disgusted faces) but also a more general negative emotion (sadness) during late, compared with early, pregnancy. Enhanced ability to encode emotional faces during late pregnancy may be an evolutionary adaption to prepare women for the protective and nurturing demands of motherhood by increasing their general emotional sensitivity and their vigilance towards emotional signals of threat, aggression and contagion. However, the results also suggest that, during late pregnancy, women's emotion processing style is similar to that seen in anxiety. The results have implications for our understanding of normal pregnant women's processing of emotional cues and their vulnerability to symptoms of anxiety.     

Performance IQ in children is associated with blood cadmium concentration in early pregnancy

ObjectiveTo investigate whether performance IQ in children is associated with maternal blood cadmium concentration in early pregnancy.MethodThe present study is a component of the Mothers’ and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project in Korea that began in 2006. The study cohort consisted of 119 children whose mothers underwent testing of blood cadmium during early pregnancy. All children were evaluated using the Korean version of the Wechsler Preschool and Primary Scale of Intelligence, revised edition (WPPSI-R), at 60 months of age. Multivariate linear regression analysis was performed to analyze the correlation between IQ in children and maternal blood cadmium concentration in early pregnancy, after adjustment for covariates.ResultsMaternal blood cadmium concentration during early pregnancy was inversely associated with performance IQ, after adjustment for covariates such as sex, educational levels of both parents, family income, and maternal BMI. Maternal blood cadmium concentration, however, was not associated with cognitive IQ.ConclusionPerformance IQ in children is associated with maternal blood cadmium concentration in early pregnancy.     

Body mass variation is negatively associated with brain size: Evidence for the fat-brain trade-off in anurans

Species can evolve diverse strategies to survive periods of uncertainty. Animals may either invest in energy storage, allowing them to decrease foraging costs, such as locomotion or risk of predation, or they may invest in better cognitive abilities helping them to flexibly adapt their behavior to meet novel challenges. Here, we test this idea of a fat-brain trade-off in 38 species of Chinese anurans by relating the coefficient of variation of body mass (CV_bodymass; as an indicator of how much animals invest into storage over the season) to brain anatomical features. After correcting for shared ancestry and body mass, we found a negative relationship between relative brain size and CV_bodymass. This indicates that anurans seem to trade-off physiological and cognitive buffering during energy shortages. As similar patterns have been reported in arboreal mammals and primates our findings suggest that the fat-brain trade-off, where animals either invest into physiological or cognitive strategies to survive harsh conditions, may be a general pattern across vertebrates.     

Evidence for early aging in the mucosal immune system

Despite recent advances in the cellular and molecular analysis of induction and regulation of mucosal immune responses, little is yet known about differences which occur in aging. To address this important issue, we have compared the mucosal and systemic immune responses of aged (12- to 14-mo- or 2-year-old) and young adult (6- to 8-wk-old) C57BL/6 mice. Both aged and young mice were immunized weekly with three oral doses of 1 mg of OVA and 10 microg of cholera toxin (CT) as mucosal adjuvant. Both groups of mice over 1 or 2 years of age showed reduced levels of Ag-specific mucosal or systemic immune responses at day 21. An Ag-specific B cell enzyme-linked immunospot assay confirmed these results at the cellular level. When the Ag-induced cytokine responses were examined at both protein and mRNA levels, CD4(+) T cells from spleen and Peyer's patches of young adult mice revealed elevated levels of IL-4 production; however, these cytokine responses were significantly diminished in aged mice. In contrast to mucosal immunization, mice s. c. immunized with OVA plus CT resulted in impaired OVA-specific but intact CT B subunit-specific immune responses in 12- to 14-mo-old mice although the responses to both Ags were depressed in 2-year-old mice. These results provide the first evidence that the development of age-associated alterations possibly occurs earlier in the mucosal immune system than in the systemic immune compartment.     

Longer life span is associated with elevated immune activity in a seasonally polyphenic butterfly

Seasonal polyphenism constitutes a specific type of phenotypic plasticity in which short‐lived organisms produce different phenotypes in different times of the year. Seasonal generations of such species frequently differ in their overall lifespan and in the values of traits closely related to fitness. Seasonal polyphenisms provide thus excellent, albeit underused model systems for studying trade‐offs between life‐history traits. Here, we compare immunological parameters between the two generations of the European map butterfly (Araschnia levana), a well‐known example of a seasonally polyphenic species. To reveal possible costs of immune defence, we also examine the concurrent differences in several life‐history traits. Both in laboratory experiments and in the field, last instar larvae heading towards the diapause (overwintering) had higher levels of both phenoloxidase (PO) activity and lytic activity than directly developing individuals. These results suggest that individuals from the diapausing generation with much longer juvenile (pupal) period invest more in their immune system than those from the short‐living directly developing generation. The revealed negative correlation between pupal mass and PO activity may be one of the reasons why, in this species, the diapausing generation has a smaller body size than the directly developing generation. Immunological parameters may thus well mediate trade‐offs between body size‐related traits.     

Blue and green egg-color intensity is associated with parental effort and mating system in passerines: support for the sexual selection hypothesis

Among several adaptive explanations proposed to account for variation in avian egg color, that related to sexual selection is of particular interest because of its possible generality. Briefly, it proposes that because biliverdin (the pigment responsible for blue-green eggshell coloration) is an antioxidant, deposition in the eggshell by laying females may signal the capacity of females to control free radicals, despite the handicap of removing this antioxidant from their body. If males adjust parental effort in response to the intensity of the blue coloration of eggs, thereby investing more in the offspring of high-quality mates, blue eggs may represent a postmating sexually selected signal in females. Here, by image and spectrophotometric analyses of the eggs of European passerines, we tested two different predictions of the hypothesis. First, variables related to intraspecific variation in parental effort (i.e., the duration of the nestling period controlled for body mass) should be positively related to the intensity of blue-green color of the eggshell across species. Second, there should be a positive relationship between intensity of blue-green color of eggs and degree of polygyny. These predictions were supported: intensity of blue-green coloration (i.e., chroma) was significantly related to the duration of the nestling period and to degree of polygyny after controlling for possible confounding variables (i.e., body mass, incubation period, and nest type) and similarity due to common descent. Nest type (hole or nonhole) also explained a significant proportion of variation in egg chroma, perhaps reflecting different selection pressures (i.e., light conditions, risk of parasitism) affecting species with the two types of nests.     

Abdominal fat mass is associated with adaptive immune activation: the CODAM Study

Abdominal fat-related activation of the innate immune system and insulin resistance (IR) are implicated in the pathogenesis of cardiovascular diseases. Recent data support an important role of the adaptive immune system as well. In this study, we investigate the association between waist circumference and markers of systemic adaptive immune activation, and the potential mediating role of innate immune activation and/or IR herein. The study population consisted of 477 (304 men) individuals (mean age: 59.4 ± 7.0 years) in whom waist circumference, HOMA2-IR (IR derived from homeostasis model assessment), and markers of innate (C-reactive protein (CRP), interleukin (IL)-6, serum amyloid A (SAA)) and adaptive (neopterin, soluble CD25 (sCD25)) immune activation were measured. These markers were compiled into an adaptive and innate immune activation score by averaging the respective z-scores. After adjustments for age, sex, glucose metabolism, smoking status, prior cardiovascular disease, and other risk factors, waist circumference was associated with the adaptive (standardized regression coefficient β = 0.12 (95% confidence intervals: 0.04-0.20)) and the innate immune activation scores (β = 0.24 (0.17-0.31)), and with HOMA2-IR (β = 0.49 (0.42-0.56)). The innate immune activation score and HOMA2-IR were also positively associated with the adaptive immune activation score (β = 0.31 (0.21-0.40) and β = 0.11 (0.02-0.21), respectively). The association between waist circumference and the adaptive immune activation score was completely abolished when further adjusted for innate immune activation and HOMA2-IR (to β = -0.01 (-0.10-0.08)), and the specific mediation "effects" attributable to each of these variables were 58% and 42%, respectively. We conclude that abdominal obesity is associated with systemic adaptive immune activation and that innate immune activation and IR constitute independent and equally important pathways explaining this association.     

Baroreflex sensitivity in obesity: relationship with cardiac autonomic nervous system activity

Objective: The aim of this study was to test the hypothesis that baroreflex sensitivity (BRS), assessed by indirect measurement of aortic pressure, is blunted in obesity. Additionally, the potential effect of cardiac autonomic nervous system (ANS) activity, aortic compliance, and metabolic parameters on BRS of obese subjects was investigated. Research Methods and Procedures: A group of 30 women with BMI >30 kg/m² and a group of 30 controls with BMI <25 kg/m² were examined. BRS was estimated by the sequence technique, cardiac ANS activity by short‐term spectral analysis of heart rate variability (HRV), and aortic compliance by the method of applanation tonometry. Results: BRS was lower in obese women (9.18 ± 3.77 vs. 19.63 ± 9.16 ms/mm Hg, p < 0.001). The median values (interquartile range) of the power of both the high‐frequency and low‐frequency components of the HRV were higher in the lean than in the obese participants [1079.2 (202.7 to 1716.9) vs. 224.1 (72.7 to 539.6) msec², p = 0.001 and 411.8 (199.3 to 798.0) vs. 235.8 (99.4 to 424.5) msec², p = 0.01 respectively]. Low‐to‐high‐frequency ratio values were higher in the obese subjects [0.82 (0.47 to 2.1) vs. 0.57 (0.28 to 0.89), p = 0.02]. Aortic augmentation values were not significantly different between lean and obese subjects. Multivariate analysis demonstrated a significant and independent association between BRS and age (p = 0.003), BMI (p < 0.001), and high‐frequency power of HRV (p < 0.001). These variables explained 72% of the variation of BRS values. Discussion: BRS is severely reduced in obese subjects. BMI, age, and the parasympathetic nervous system activity are the main determinants of BRS. Baroreflex behavior is of clinical relevance because an attenuated BRS represents a negative prognostic factor in cardiovascular diseases, which are common in obesity.     

Hormonal correlates of siblicide in Nazca boobies: support for the Challenge Hypothesis

The androgen hormone testosterone (T) mediates vertebrate aggression in many contexts and according to the Challenge Hypothesis is up-regulated during social challenges. While originally applied to challenges experienced by breeding adults, we show for the first time that T is similarly up-regulated during deadly sibling aggression in young birds. When two nestling Nazca boobies hatch, one--usually the older chick--virtually always kills the other chick by pushing it from the nest. We compared concentrations of T, dehydroepiandrosterone (DHEA; a precursor of T), and corticosterone (Cort; a stress hormone) of chicks at various stages. T was elevated during fights in both chicks in two-chick broods, but not before and after fights, and not in chicks lacking a nest mate. DHEA was elevated 1 day after hatching and declined with age but appeared not to vary in concert with aggression. Cort did not vary across fighting and nonfighting periods. In conjunction with an earlier study [Tarlow, E.M., Wikelski, M., Anderson, D.J., 2001. Hormonal correlates of siblicide in Galapagos Nazca boobies. Horm. Behav. 40:14-20], these results indicate that T is temporarily up-regulated around the time of fights, as predicted by the Challenge Hypothesis. Our data suggest a general role for T during challenges at any time in life, not just during breeding.     

The cell-mediated immune response to Neospora caninum during pregnancy in the mouse is associated with a bias towards production of interleukin-4

Neospora caninum is an obligate intracellular protozoan parasite which is efficiently transmitted transplacentally in cattle where it may cause abortion. A pregnant mouse model was used to characterise the immune response following N. caninum infection; the response in non-pregnant and pregnant mice was compared. Spleen cells from both infected/non-pregnant and infected/pregnant mice produced interferon-gamma, interleukin-12 and tumour necrosis factor alpha; however, the levels of these Th1 cytokines were lower in infected/pregnant mice. Infected/non-pregnant and infected/pregnant mice also produced the Th2 cytokine interleukin-10; however, there was no trend toward a decrease of this in pregnant mice. Interleukin-4 was exclusively produced at high levels by infected/pregnant mice and thus appears responsible for the observed decline in Th1 cytokine production in pregnant mice. A bias towards Th2 cytokines such as IL-4 and IL-10 is normally associated with the maintenance of a viable pregnancy, and not with the control of protozoal infections. Consequently, the importance and role of cytokines and cell-mediated immunity in the control of transplacental transmission and foetal loss due to N. caninum infection are discussed.     

Maternal exposure to paternal antigens can modulate the foetus immune system and is associated with reduced atopy in the childhood

The influence of the maternal immune system on pregnancy and on the foetus immune system have given rise to a variety of observations and interesting hypotheses. For example, the higher prevalence of atopy in first-born children as compared to their brotherhood is known as the “birth order effect”. The “hygienic hypothesis” states that more hygienic live conditions, and consequently reduced exposure to pathogens in young age (included the period of foetal development), increases the risk of atopy. Here we review the ideas concerning maternal exposure to paternal antigens and immunomodulation. In particularly, we discuss the idea that this phenomenon may induce a regulatory environment in women that interfere with the developing foetal immune system. This regulatory environment could be responsible for protecting children to the development of atopy during adulthood. We propose that maternal exposure to paternal antigens through different situations, such as pregnancy, repeated exposure to sperm or Paternal Leukocyte Immunization (PLI) would combine the “birth order effect” and the “hygienic hypothesis” and thus lower the risk to atopy in children through the transference of a regulatory environment to the foetus.     

Influence of pre-ovulatory insemination and early pregnancy on the infiltration by cells of the immune system in the sow endometrium

The aim of this study was to investigate the distribution of leukocytes in the sow endometrium following insemination and during early pregnancy. Cross-bred multiparous sows (Swedish Landrace x Swedish Yorkshire) were artificially inseminated (AI) once at 20-15 h before ovulation. Blood samples were collected from the jugular vein 1 h before slaughter for analyses of oestradiol-17beta and progesterone levels. The sows were slaughtered at 5-6 h (group I, n = 4) after AI or at different times after ovulation: 20-25 h (group II, n = 4), 70 h (group III, n = 4), day 11 (group IV, n = 3; first day of standing oestrus = day 1) and day 19 (group V, n = 3). Uterine horns were flushed to control for the presence of spermatozoa and neutrophils (groups I-IV) and/or for recovery of oocytes and/or embryos (groups II-IV, control of pregnancy). Mesometrial uterine samples were fixed, embedded in plastic resin and stained with toluidine blue. The surface and glandular epithelia as well as subepithelial and glandular connective tissue layers were examined by light microscopy. A marked number of neutrophils and spermatozoa were observed in the flushings from the uterine horns of sows slaughtered at 5-6 h after insemination. All animals slaughtered after ovulation were pregnant but no morphological effect of pregnancy was observed until day 11. In the surface epithelium, the largest numbers of intraepithelial lymphocytes were found in groups II and III, the smallest number was found in group V. The largest number of lymphocytes within the glandular epithelium was found in group III. The largest number of macrophages within the surface and glandular epithelia were found in group I. Neutrophils were found within the surface epithelium only in groups I and II. In the subepithelial connective tissue layer, a high infiltration of neutrophils was found in groups I and II while the largest number of eosinophils was found in group IV. The largest number of lymphocytes was observed in group V. In conclusion, this study showed a variation in the infiltration and distribution of neutrophils, lymphocytes, macrophages, eosinophils and plasma cells in the endometrium following insemination and during different stages of early pregnancy. Particularly, the pattern of lymphocyte presence on day 19 of pregnancy, indicate that the lymphocyte function may play a role during embryonic attachment in the pig.