Maternal high-fat diet is associated with altered pancreatic remodelling in mice offspring

Purpose

To investigate whether a maternal high-fat diet (HF) during pregnancy and/or suckling periods predisposes adult C57BL/6 mice offspring to morphological pancreatic modifications.

Methods

Male pups were divided into 5 groups: SC (standard chow)—from dams fed SC during gestation and lactation, maintaining an SC diet from postweaning to adulthood; G—from dams fed HF diets during gestation; L—from dams fed HF diets during lactation; GL—from dams fed HF diets during gestation and lactation; and GL/HF—from dams fed HF diets during gestation and lactation, maintaining an HF diet from postweaning to adulthood. We analysed body mass (BM), plasma insulin, pancreas and adipose tissue structures.

Results

During the entire experiment, the SC group had the lowest BM. However, GL/HF offspring were heavier than the other groups. This weight gain was also accompanied by adipocyte hypertrophy. At 3 months, G offspring showed an increased insulin levels and impairment in carbohydrates metabolism. Furthermore, pancreatic islets were hypertrophied in G, GL and GL/HF offspring in comparison with SC offspring.

Conclusion

HF diet administration during the gestation period is more harmful than during the lactation period, exerting deleterious effects on pancreatic morphology in addition to larger fat deposits in adult mice offspring.     

High-fat feeding increases hepatic vitamin C synthesis and its circulatory mobilization in mice

Purpose

Vitamin C (vitC) deficiency has been linked to obesity and increased risk of cardiovascular disease and type 2 diabetes. Whereas humans are unable to synthesize vitC and therefore to compensate for increased turnover, we investigated whether mice—independent of dietary vitC—are able to modulate their vitC homeostasis during high-fat (HF) feeding.

Methods

Twenty-five male 5-week-old C57BL/6 mice were fed high- or low-fat diets for 14 weeks. An oral glucose tolerance test (OGTT) was performed after 12 weeks of intervention. Terminal fasting plasma samples were analyzed for insulin, glucose and vitC concentrations. Hepatic vitC concentration and gulonolactone oxidase (GLO) capacity, as a measure of vitC de novo biosynthesis, were analyzed in liver homogenates.

Results

HF diet significantly increased plasma concentrations of vitC compared with a control diet low in fat (P < 0.05). Hepatic de novo biosynthesis of vitC was upregulated (P < 0.05) as measured by GLO capacity, and liver vitC was reduced (P < 0.01) by HF feeding compared with low-fat feeding. Moreover, plasma concentration of vitC was significantly positively correlated with plasma glucose and insulin concentrations as well as glucose intolerance as measured by an OGTT (P < 0.05).

Conclusion

Our data suggest that mice have the ability to adapt to increased vitC turnover induced by HF diet by increasing hepatic de novo synthesis and mobilization.     

Dietary cocoa ameliorates obesity-related inflammation in high fat-fed mice

Purpose

To investigate the effect of cocoa powder supplementation on obesity-related inflammation in high fat (HF)-fed obese mice.

Methods

Male C57BL/6J (n = 126) were fed with either low-fat (LF, 10 % kcal from fat) or HF (60 % kcal from fat) diet for 18 weeks. After 8 weeks, mice from HF group were randomized to HF diet or HF diet supplemented with 8 % cocoa powder (HF–HFC group) for 10 weeks. Blood and tissue samples were collected for biochemical analyses.

Results

Cocoa powder supplementation significantly reduced the rate of body weight gain (15.8 %) and increased fecal lipid content (55.2 %) compared to HF-fed control mice. Further, cocoa supplementation attenuated insulin resistance, as indicated by improved HOMA-IR, and reduced the severity of obesity-related fatty liver disease (decreased plasma alanine aminotransferase and liver triglyceride) compared to HF group. Cocoa supplementation also significantly decreased plasma levels of the pro-inflammatory mediators interleukin-6 (IL-6, 30.4 %), monocyte chemoattractant protein-1 (MCP-1, 25.2 %), and increased adiponectin (33.7 %) compared to HF-fed mice. Expression of pro-inflammatory genes (Il6, Il12b, Nos2, and Emr1) in the stromal vascular fraction (SVF) of the epididymal white adipose tissue (WAT) was significantly reduced (37–56 %) in the cocoa-supplemented mice.

Conclusions

Dietary supplementation with cocoa ameliorates obesity-related inflammation, insulin resistance, and fatty liver disease in HF-fed obese mice, principally through the down-regulation of pro-inflammatory gene expression in WAT. These effects appear to be mediated in part by a modulation of dietary fat absorption and inhibition of macrophage infiltration in WAT.     

A high intake of dietary fiber influences C-reactive protein and fibrinogen,but not glucose and lipid metabolism,in mildly hypercholesterolemic subjects

Purpose

The aim of the study was to investigate how a diet high in dietary fiber, with several fiber sources included, modulates glucose and lipid metabolism and the inflammatory response in humans.

Methods

Subjects (n = 25) aged 58.6 (1.1) years (mean and SD) with a BMI of 26.6 (0.5) kg/m² and a total cholesterol (TC) of 5.8 (0.1) mmol/L (mean and SEM) were given a high fiber (HF) and low fiber (LF) diet, in a randomized controlled 5-week crossover intervention, separated by a 3-week washout. The HF diet consisted of oat bran, rye bran, and sugar beet fiber incorporated into test food products; one bread roll, one ready meal, and two beverages consumed daily. Equivalent food products, without added fibers, were provided in the LF diet.

Results

Total dietary fiber intake was 48.0 g and 30.2 g per day for the HF and LF diet, respectively. Significant reduction in C-reactive protein (CRP) was observed between the diets (P = 0.017) and a significant reduction in fibrinogen within the HF diet (P = 0.044). There were no significant effects in other measured circulating cytokines or in glucose, insulin, and lipid levels.

Conclusions

Our study suggests that a 5-week high dietary fiber intake of oat bran, rye bran, and sugar beet fiber might reduce the low-grade inflammatory response measured as CRP which could, together with reduced fibrinogen, help to prevent the risk of cardiovascular disease.     

Enhanced sensitivity of skeletal muscle growth in offspring of mice long-term selected for high body mass in response to a maternal high-protein/low-carbohydrate diet during lactation

Aim

To investigate the effects of a high-protein/low-carbohydrate diet fed to mice of different genotypes during pregnancy and/or lactation on offspring skeletal muscle growth and metabolism.

Methods

Pregnant mice from strains selected for high body mass (DU6) or endurance running performance (DUhLB) and from an unselected control strain (DUK) were fed iso-energetic diets containing 20 % (C) or 40 % protein and low carbohydrate (HP) from mating to weaning at day 21 of age. At birth, offspring were cross-fostered resulting in different exposure to maternal prenatal-preweaning diets (C–C, HP–C, C–HP, HP–HP). Rectus femoris muscle of male mice (n = 291) was examined at day 23, 44, 181 and 396 of age for cellular growth and metabolism.

Results

At day 23 of age, body and muscle growth was retarded by 30–40 % (P < 0.0001) in response to the C–HP and HP–HP, but not to the HP–C diet, due to reduced fibre size (P < 0.0001) but not fibre number. DNA was highly reduced in DU6, less in DUhLB, but not in DUK muscle (strain × diet; P < 0.0001). Despite some compensation, muscle growth was still impaired (P < 0.001) in adulthood (day 44; day 181), but at senescence only in DU6 mice (strain × diet; P < 0.05). Only at weaning, isocitrate and lactate dehydrogenase activities were increased or decreased (P < 0.0001), respectively, without influence on fibre type composition.

Conclusion

A high-protein/low-carbohydrate diet fed to dams during lactation, but not during pregnancy, retards skeletal muscle growth in offspring with greater response of a heavy, obese compared with a physically fit and a control genotype and causes a transient shift towards oxidative versus glycolytic muscle metabolism.     

Evidence of altered biochemical composition in the hearts of adult intrauterine growth-restricted rats

Purpose

Epidemiological studies clearly link intrauterine growth restriction with increased risk of cardiac disease in adulthood. The mechanisms leading to this increased risk are poorly understood; remodeling of the myocardium is implicated. The aim was to determine the effect of early life growth restriction on the biochemical composition of the left ventricular myocardium in adult rats.

Methods

Wistar Kyoto dams were fed either a low protein diet (LPD; 8.7 % casein) or normal protein diet (NPD; 20 % casein) during pregnancy and lactation; from weaning, the offspring were fed normal rat chow. At 18 weeks of age, the biochemical composition of the hearts of NPD control (n = 9) and LPD intrauterine growth-restricted (n = 7) offspring was analyzed using Fourier Transform Infrared (FTIR) micro-spectroscopy.

Results

Body weights at postnatal day 4 were significantly lower and remained lower throughout the experimental period in the LPD offspring compared to controls. FTIR analysis of the infrared absorption spectra across the whole “fingerprint” region (1,800–950 cm^?1) demonstrated wider variation in absorbance intensity in the LPD group compared to controls. In particular, there were marked differences detected in the protein (1,540 cm^?1), lipid (1,455 and 1,388 cm^?1), proteoglycan (1,228 cm^?1) and carbohydrate (1,038 cm^?1) bands, indicating increased lipid, proteoglycan and carbohydrate content in the growth-restricted myocardium.

Conclusion

In conclusion, changes in the biochemical composition of the myocardium provide a likely mechanism for the increased vulnerability to cardiovascular disease in offspring that were growth restricted in early life.     

Effect of dietary fatty acid composition on substrate utilization and body weight maintenance in humans

Background/purpose

Dietary fat content is a primary factor associated with the increase in global obesity rates. There is a delay in achieving fat balance following exposure to a high-fat (HF) diet (≥ 40 % of total energy from fat) and fat balance is closely linked to energy balance. Exercise has been shown to improve this rate of adaptation to a HF diet. Recently, however, the role of dietary fatty acid composition on energy and macronutrient balance has come into question.

Methods

We chose studies that compared monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and saturated fatty acids (SFA). We have reviewed studies that measured diet-induced thermogenesis (DIT), energy expenditure (EE), or fat oxidation (FOx) in response to a HF meal challenge, or long-term dietary intervention comparing these fatty acids.

Results

While single-meal studies show that SFA induce lower DIT and FOx compared to unsaturated fats, the effect of the degree of unsaturation (MUFA vs. PUFA) appears to yet be determined. Long-term dietary interventions also support the notion that unsaturated fats induce greater EE, DIT, and/or FOx versus SFA and that a high MUFA diet induces more weight loss compared to a high SFA diet. Sex and BMI status also affect the metabolic responses to different fatty acids; however, more research in these areas is warranted.

Conclusion

SFA are likely more obesigenic than MUFA, and PUFA. The unsaturated fats appear to be more metabolically beneficial, specifically MUFA ≥ PUFA > SFA, as evidenced by the higher DIT and FOx following HF meals or diets.     

Acute effects of high-protein versus normal-protein isocaloric meals on satiety and ghrelin

Purpose

The objective was to compare isocaloric high-protein (HP) test meals with normal-protein (NP) test ones on satiety and ghrelin in human being.

Methods

Systematic searches were conducted by using PubMed, Cochrane library, EMBASE, and HighWire Press to identify randomized, crossover trials that investigated the acute effects of isocalorically prescribed HP versus NP test meals on satiety and ghrelin.

Results

Pooled analyses showed that subjects with HP test meals had a significantly higher acute satiety area under the curve (AUC) than those with NP test meals (P < 0.001). Conversely, the former had a markedly lower level of acute ghrelin at 180 min as well as acute glucose AUC, although they had a notably higher glucose at 180 min (P = 0.008).

Conclusions

The meta-analysis showed that the acute consumption of HP did produce more satiety. In addition, relative to NP test meals, HP test ones may be useful in regulating postprandial glucose, whereas a significantly higher preprandial glucose combined with a lower concentration of ghrelin may contribute to the decrease in ad libitum caloric intake.     

Low iron status as a factor of increased bone resorption and effects of an iron and vitamin D-fortified skimmed milk on bone remodelling in young Spanish women

Purpose

This study aimed to determine whether there is a relationship between iron status and bone metabolism, and to compare the effects of the consumption, as part of the usual diet, of an iron or iron and vitamin D-fortified skimmed milk on bone remodelling in iron-deficient women.

Methods

Young healthy iron-deficient or iron-sufficient women (serum ferritin ≤30 ng/mL or >30 ng/mL, respectively) were recruited. Iron-deficient women were assigned to a nutritional intervention consisting of a randomised, controlled, double-blind, parallel design trial of 16 weeks during winter. They consumed, as part of their usual diet, an iron (Fe group, n = 54) or iron and vitamin D-fortified (Fe+D group, n = 55) flavoured skimmed milk (iron, 15 mg/day; vitamin D₃, 5 μg/day, 200 IU). The iron-sufficient women followed their usual diet without supplementation (R group, n = 56). Dietary intake, body weight, iron biomarkers, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), procollagen-type 1 N-terminal propeptide (P1NP), and aminoterminal telopeptide of collagen I (NTx) were determined.

Results

Negative correlations were found between baseline log-ferritin and log-NTx (p < 0.001), and between transferrin and P1NP (p = 0.002). Serum 25OHD increased (from 62 ± 21 to 71 ± 21 nmol/L, mean ± SD, p < 0.001) while P1NP and NTx decreased in Fe+D during the assay (p = 0.004 and p < 0.001, respectively). NTx was lower in Fe+D compared to Fe at week 8 (p < 0.05) and was higher in Fe and Fe+D compared to R throughout the assay (p < 0.01). PTH did not show changes.

Conclusions

Iron deficiency is related with higher bone resorption in young women. Consumption of a dairy product that supplies 5 μg/day of vitamin D₃ reduces bone turnover and increases circulating 25OHD to nearly reach an optimal vitamin D status, defined as 25OHD over 75 nmol/L.     

Consumption of wheat bran modified by autoclaving reduces fat mass in hamsters

Purpose

To investigate the effect that wheat bran modified by autoclaving (MWB) had on reducing fat accumulation in hamsters fed a hypercholesterolemia- and obesity-inducing diet.

Methods

Male hamsters (n = 45) were randomized into 3 groups and fed a hypercholesterolemia- and obesity-inducing diet with or without 10 % standard wheat bran or MWB for 28 days. Our outcome measures included body composition measured by DXA, oxygen consumption and plasma lipids and glucose concentrations.

Results

Animals fed the MWB diet had lower % fat mass (49.8 vs. 53.4 %; p = 0.02) and higher % lean body mass (47.2 vs. 44.1 %; p = 0.02) compared with controls despite no differences in food intake or weight gain. Additionally, plasma glucose tended to be lower (6.9 vs. 8.5 mmol/l; p < 0.08) in the MWB animals compared with controls.

Conclusions

Our data suggest that the compositional changes in autoclaved wheat bran, specifically solubility of phenolic antioxidants and fiber, may have contributed to the lower fat accumulation in our animals. Further study is needed to determine whether the exact mechanism involved increased lipolysis and energy utilization from adipose.     

Vitamin B12 as a potential compliance marker for fish intake

Objectives

The aim of the present study was to investigate whether the following four markers: vitamin B₁₂, selenium, vitamin D, and parvalbumin may be used as compliance markers for fish intake.

Methods

Blood samples from a randomized cross-over herring intervention study (n = 32) were analysed by HPLC and immunochemistry. The criteria were that plasma or serum concentrations of candidate compliance markers after the herring diet should increase significantly compared to starting concentrations. In addition, the reference meat diet should not yield an increase in plasma concentration of the candidate marker.

Results

Vitamin B₁₂ and selenium met the set criteria for indicating a correlation between the marker and fish intake with significant increases in serum concentrations at 8.9 % (p = 0.008) and 4.6 % (p = 0.02), respectively, after a 6-week herring intervention (5 meals a week). Parvalbumin and 25-hydroxy vitamin D₃ levels did not increase significantly after the herring interventions.

Conclusions

Vitamin B₁₂ may be suitable as a compliance marker for fish intake. Although selenium also met the criteria, the change in selenium serum concentrations was small compared to the change in vitamin B₁₂ levels.     

Ilex paraguariensis (yerba mate) improves endocrine and metabolic disorders in obese rats primed by early weaning

Purpose

We showed that early weaned rats developed obesity, hyperleptinemia, leptin and insulin resistance at adulthood. Here, we studied the potential beneficial effects of Ilex paraguariensis aqueous solution upon body composition, glycemia, lipid and hormonal profiles, leptin signaling and NPY content.

Methods

To induce early weaning, lactating rats’ teats were blocked with a bandage to interrupt lactation during the last 3 days (EW group), while control offspring had free access to milk throughout lactation (C group). In postnatal day (PN) 150, EW offspring were subdivided into: EW and EW+ mate groups treated, respectively, with water or yerba mate aqueous solution (1 g/kg BW/day, gavage) during 30 days. C offspring received water for gavage. In PN180, offspring were killed.

Results

EW+ mate group presented lower body weight (?10 %), adipose mass (retroperitoneal:?40 % and epididymal:?44 %), total body fat (?43 %), subcutaneous fat (?46 %), visceral adipocyte area (?21 %), triglyceridemia (?31 %) and hypothalamic NPY content (?37 %) compared to EW group. However, hyperglycemia and lower HDL-c levels observed in EW group were not reverted with mate treatment. Although the hyperleptinemia, lower hypothalamic JAK2 and pSTAT3 content of EW group were not corrected by mate treatment, the hyperphagia and higher hypothalamic SOCS-3 content were normalized in EW+ mate group, indicating that the central leptin resistance could be restored.

Conclusion

Thus, the therapy with yerba mate solution was capable to reverse abdominal obesity, leptin resistance and hypertriglyceridemia, suggesting an important role of this bioactive component in the management of obesity in this programming model.     

Maternal caffeine administration leads to adverse effects on adult mice offspring

Purpose

This study aimed to evaluate the role of caffeine chronic administration during gestation of C57BL/6 mice on cardiac remodeling and the expression of components of the renin-angiotensin system (RAS) in male offspring as adults.

Methods

Pregnant C57BL/6 female mice were divided into two groups (n = 10): Control group (C), dams were injected with the vehicle only (saline 0.9 % NaCl); Caffeine group (CF), dams received daily a subcutaneous injection of 20 mg/kg of caffeine/day (1 mg/mL saline). Pups had free access to standard chow since weaning to 3 months of age, when they were killed.

Results

CF group showed increased energy expenditure (+7 %) with consequent reduction in body mass (BM) gain (?18 %), increased blood pressure (+48 %), and higher heart rate (+10 %) than C group. The ratio between LV mass/BM was greater (+10 %), with bigger cardiomyocytes (+40 %), and reduced vascularization (?25 %) in CF group than in C group. In the LV, the expression of angiotensin-converting enzyme (+30 %), Angiotensin II (AngII) (+60 %), AngII receptor (ATR)-1 (+77 %) were higher, and the expression of ATR-2 was lower (?46 %; P < 0.05) in CF group than in C group. In the kidney, the expressions of renin (+128 %) and ATR-1 (+88 %) were higher in CF group than in C group.

Conclusions

Chronic administration of caffeine to pregnant dams led to persistent activation of local RAS in the kidney and heart of the offspring, which, in turn, leads to high BP and adverse cardiac remodeling. These findings highlight the urge to encourage pregnant women to avoid food or medicines containing caffeine.     

Cost Utility of Telaprevir–PR (Peginterferon–Ribavirin) Versus Boceprevir–PR and Versus PR Alone in Chronic Hepatitis C in The Netherlands

Background

The hepatitis C virus may lead to cirrhosis, liver cancer, liver transplant, and increased mortality. With standard treatment peginterferon-alpha and ribavirin (PR), sustained viral response (SVR) was less than 50 %. SVR rates improve greatly when PR is combined with telaprevir or boceprevir.

Objectives

The aim of this study was to assess the cost utility of telaprevir-peginterferon-ribavirin (TPR) versus PR and boceprevir-peginterferon-ribavirin (BPR) in treatment-naïve (TN) and treatment-experienced (TE) adults with chronic hepatitis C in the Netherlands.

Methods

A Markov model with a lifelong time horizon and annual cycles was developed. Clinical data stemmed from phase III trials (TPR vs PR, BPR vs PR). A mixed treatment comparison (MTC) was developed to compare TPR and BPR indirectly. Unit costs and utilities based on EQ-5D were established in a Dutch cross-sectional study. Cost per quality-adjusted life-years (QALYs) was calculated according to the societal perspective.

Results

Treating TN patients with TPR generates 1.12 additional QALYs with €333 additional cost compared with PR, resulting in an incremental cost–utility ratio of €299/QALY. In TE patients, TPR dominates PR with cost savings (?€7,819) and 1.63 additional QALYs. TPR dominates BPR yielding additional QALYs (0.26 in TN; 0.71 in TE) and cost savings (?€7,296, ?€18,144, respectively).

Conclusions

TPR seems a cost-effective alternative to PR in TN patients and dominant in TE patients. TPR was a dominant, more effective and less costly alternative to BPR in both patient types. The cost effectiveness of both TPR and BPR is well below generally accepted willingness-to-pay thresholds and may be considered cost effective.     

Associations of infant milk feed type on early postnatal growth of offspring exposed and unexposed to gestational diabetes in utero

Purpose

Infants on prolonged breastfeeding are known to grow slower during the first year of life. It is still unclear if such effects are similar in offspring exposed to gestational diabetes (GDM) in utero. We examined the associations of infant milk feeding on postnatal growth from birth till 36 months of age in offspring exposed and unexposed to GDM.

Methods

Pregnant mothers undertook 75 g 2-h oral glucose tolerance tests at 26–28 weeks of gestation for GDM diagnosis. Up to 9 measurements of offspring weight and length were collected from birth till 36 months, and interviewer-administered questionnaires were used to ascertain the duration of breastfeeding.

Results

There was a statistically significant interaction between GDM status and breastmilk intake by any (p _interaction = 0.038) or exclusive/predominant breastfeeding (p _interaction = 0.035) for the outcome of conditional weight gain. In offspring of non-GDM mothers (n = 835), greater breastmilk intake (BF ≥ 4 milk months) was associated with lower conditional gains in weight [B (95 % CI) ?0.48 (?0.58, ?0.28); p < 0.001] within the first year of life, as well as decreasing weight SDS velocity [?0.01 (?0.02, ?0.005); p < 0.001] and BMI SDS velocity [?0.008 (0.01, ?0.002); p = 0.008] across age in the first 36 months. In offspring of GDM mothers (n = 181), however, greater breastmilk intake was associated with increased conditional gains in weight [0.72 (0.23, 1.20); p = 0.029] and BMI SDS [0.49 (0.04, 0.95); p = 0.04] in the first 6 months and did not demonstrate the decreasing weight and BMI SDS velocity observed in offspring of non-GDM mothers.

Conclusions

The reduced weight gain in the first year of life conferred by greater breastmilk intake in non-GDM children was not observed in GDM children.

Clinical trial registration

This study is registered under the Clinical Trials identifier NCT01174875; http://www.clinicaltrials.gov/ct2/show/NCT01174875?term=GUSTO&rank=2.

     

Phytosterols protect against diet-induced hypertriglyceridemia in Syrian golden hamsters

Background

In addition to lowering LDL-C, emerging data suggests that phytosterols (PS) may reduce blood triglycerides (TG), however, the underlying mechanisms are not known.

Methods

We examined the TG-lowering mechanisms of dietary PS in Syrian golden hamsters randomly assigned to a high fat (HF) diet or the HF diet supplemented with PS (2%) for 6 weeks (n?=?12/group). An additional subset of animals (n?=?12) was provided the HF diet supplemented with ezetimibe (EZ, 0.002%) as a positive control as it is a cholesterol-lowering agent with known TG-lowering properties.

Results

In confirmation of diet formulation and compound delivery, both the PS and EZ treatments lowered (p?<?0.05) intestinal cholesterol absorption (24 and 31%, respectively), blood non-HDL cholesterol (61 and 66%, respectively), and hepatic cholesterol (45 and 55%, respectively) compared with the HF-fed animals. Blood TG concentrations were lower (p?<?0.05) in the PS (49%) and EZ (68%)-treated animals compared with the HF group. The TG-lowering response in the PS-supplemented group was associated with reduced (p?<?0.05) intestinal SREBP1c mRNA (0.45 fold of HF), hepatic PPARα mRNA (0.73 fold of HF), hepatic FAS protein abundance (0.68 fold of HD), and de novo lipogenesis (44%) compared with the HF group. Similarly, lipogenesis was lower in the EZ-treated animals, albeit through a reduction in the hepatic protein abundance of ACC (0.47 fold of HF).

Conclusions

Study results suggest that dietary PS are protective against diet-induced hypertriglyceridemia, likely through multiple mechanisms that involve modulation of intestinal fatty acid metabolism and a reduction in hepatic lipogenesis.     

The dietary form of choline during lactation affects maternal immune function in rats

Purpose

The present study was designed to determine the effects of both choline form and availability on maternal immune function during lactation.

Methods

Sprague–Dawley rats were randomized to one of the three diets 24–48 h before parturition and fed ad libitum until 21 days postnatal: 1 g/kg choline as free choline (C, n = 11), the current form, and amount of choline in commercial diets; 1 g/kg choline as phosphatidylcholine (PC1, n = 11); or 2.5 g/kg choline as PC (PC2.5, n = 8). Choline metabolites in offspring stomach contents were quantified. At 21 days, lymphocytes from mothers’ mesenteric lymph nodes and spleens were isolated and phenotypes and ex vivo cytokine production after mitogen exposure were determined.

Results

There was a higher proportion of choline and a lower proportion of lyso-PC in stomach contents (representing dam’s milk) of C pups compared to PC1. In the mesenteric lymph nodes, feeding PC1 compared to C led to a higher IL-2 production after Concanavalin A (ConA) stimulation and a higher proportion of T cells (CD3+) and a lower proportion of B cells [immunoglobulin (Ig)κ, CD45RA+, and IgM+; P < 0.05]. Splenocytes from the PC1 group produced more IL-6 and TNF-α after lipopolysaccharides stimulation compared to C (P < 0.05). Splenocytes from the PC2.5 group produced more IL-2 and IL-6 after ConA stimulation compared to PC1 (P < 0.05).

Conclusions

Feeding choline as PC in the maternal diet improved the ability of immune cells to respond ex vivo to mitogens and increasing the amount of PC in the diet further improved T cell proliferation.

     

Comparing PROMIS computer-adaptive tests to the Brief Symptom Inventory in patients with prostate cancer

Purpose

This study assessed whether the Patient-Reported Outcomes Measurement Information System (PROMIS) computer-adaptive tests (CATs) provided results similar to those of the Brief Symptom Inventory (BSI) with a low patient burden.

Methods

Secondary data analysis of 136 prostate cancer patients who completed the 53-item BSI and the PROMIS CATs assessing depression, anxiety, and hostility.

Results

The PROMIS CATs and BSI correlated significantly in measures of depression (.85), anxiety (.76), and anger/hostility (.66; p < .001 for all). Using our BSI cutoff points for depression, anxiety, and anger/hostility, ROC analysis yielded areas under the curve of .966 [standard error (SE) = .014, p < .001], .975 (SE = .012, p < .001), and .952 (SE = .027, p < .001), respectively.

Conclusions

PROMIS CATs were highly correlated with the BSI subscales, indicating that the CATs performed well compared with the BSI, a widely used psychosocial measure.     

Impact of a functionalized olive oil extract on the uterus and the bone in a model of postmenopausal osteoporosis

Purpose

The Mediterranean diet rich in fruits, vegetables and olive oil has been related to a lower osteoporosis incidence and accordingly to a reduced fracture risk. These observations might be mediated by the active constituents of extra virgin olive oil, and especially polyphenols. In the context of exploring the features of olive oil active constituents on postmenopausal osteoporosis, an extra virgin olive oil total polyphenolic fraction (TPF) was isolated and its effect on the bone loss attenuation was investigated.

Methods

Female Lewis rats were ovariectomized and fed a diet enriched with a total phenolic extract of extra virgin olive oil in a concentration of 800 mg/kg diet.

Results

Oleocanthal, one compound of the polyphenolic fraction, showed a higher relative estrogen receptor binding affinity to the ERα compared to the ERβ. While the TPF only slightly induced the uterine wet weight (490.7 ± 53.7 vs. 432.7 ± 23, p = 0.058), TPF regulated estrogen response genes in the uterus (progesterone receptor, antigen identified by monoclonal antibody Ki67, complement C3). Comparing the quantified bone parameters, the oral TPF substitution did not attenuate the ovariectomy-induced bone loss.

Conclusions

The administration of extra virgin olive oil polyphenols regulated uterine estrogen response marker genes in an E2-agonistic manner. The bone loss induced by estrogen ablation was not mitigated by treatment with the polyphenolic extract.