Slow Weight Gain Research Articles

Accuracy of growth chart use in monitoring and assessing under-nutrition in Kenya

Aims To find out how well healthcare workers in Kenya plot and interpret information on growth charts. Methods Doctors and clinical officers (12), nurses, nutritionists and community health care workers (27) who were actively involved in growth monitoring were surveyed at primary care clinics around Nairobi, Kenya in June 2011. They completed questionnaires which included plotting of weights at ages 2, 6 and 9 months using the road to health chart (RTH) currently in use in Kenya and interpretation of 8 plotted scenarios permutated through 2 versions of the questionnaire, with each respondent rating two growth trajectories from a well baby clinic and two for children being treated for malnutrition. Results There were high levels of plotting errors; up to 78% (29) plotted weights less than 0.5 kg and 41% (16) plotted ages more than 0.5 months from the true value. This seemed to reflect the difficulty of plotting on the RTH chart. Nurses and nutritionists were rather more accurate in plotting charts compared to doctors and clinical officers. From the well-baby clinic scenario, 30% (18 out of 60) correctly identified a slow weight trajectory (fall of 2 weight SD) while 65% (11 out of 17) recognised steady growth. In the malnutrition clinic scenarios 39% (15 out of 39) recognised catch up growth (rise of 1 weight SD). For children seen in well baby clinics 70% (41 out of 59) recognised the need to offer extra care to a child with slow weight gain but 57% (9 out of 16) stated extra care was needed for a small child who had been growing steadily (−2 SD). For the malnutrition clinic scenario, 94% (36 out of 38) healthcare workers recognised that a child without catch up required extra care, but 72% (32 out of 39) also felt this was needed in a child with catch up growth. Conclusion Growth charts were not plotted accurately, partly due to poor chart design. Healthcare workers did not seem to discriminate between size and weight gain, with the result that they seemed to be concerned about healthy growth patterns when seen in relatively small children.

Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 Regulates Macrophage-Mediated Inflammatory Responses (172.35)

Abstract Calcium/calmodulin-dependent Kinase Kinase 2 (CaMKK2) plays a key role in regulating food intake and energy expenditure at least in part by its actions in hypothalamic neurons. Previously we showed that loss of CaMKK2 protected mice from high fat diet (HFD)-induced obesity and glucose intolerance. However, whereas pair-feeding HFD to WT mice to match food consumption of CAMKK2-null mice slowed weight gain, it failed to protect from glucose intolerance. Here we show that relative to WT mice, HFD-fed CaMKK2-null mice are protected from inflammation in adipose and remain glucose tolerant. Moreover, loss of CaMKK2 also protected mice from endotoxin shock and fulminant hepatitis. We explored the expression of CaMKK2 in immune cells, and found it to be restricted to those of the monocyte/macrophage lineage. CaMKK2-null macrophages exhibited a remarkable deficiency to spread, phagocytize bacteria and synthesize cytokines in response to the Toll Like Receptor 4 (TLR4) agonist lipopolysaccharide (LPS). Mechanistically, loss of CaMKK2 uncoupled the TLR4 cascade from activation of protein tyrosine kinase 2 (PYK2; also known as PTK2B). Our findings uncover an important function for CaMKK2 in mediating mechanisms that control the amplitude of macrophage inflammatory responses to excess nutrients or pathogen derivatives.

Human Milk Adiponectin Affects Infant Weight Trajectory During the Second Year of Life

Serum adiponectin (APN) is associated with lower childhood obesity, and APN concentration in human milk is associated with slower growth during active breast-feeding. We examined infant weight gain in the second year of life after exposure to high or low levels of mother's milk APN. Breast-feeding mother-infant pairs were recruited in Mexico City and studied for 2 years; 192 infants with at least 12 months' follow-up were analyzed. Monthly milk samples were assayed for APN; mothers were classified as producing high or low levels of milk APN. Infant and maternal serum APN were assessed during year 1. Infant anthropometry was measured monthly (year 1) or bimonthly (year 2), and World Health Organization z scores were calculated. Longitudinal adjusted models assessed weight-for-age and weight-for-length z score trajectories from 1 to 2 years. Maternal serum APN modestly correlated with milk APN (r=0.37, P<0.0001) and infant serum APN (r=0.29, P=0.01). Infants exposed to high milk APN experienced increasing weight-for-age and weight-for-length z scores between age 1 and 2 years in contrast to low milk APN exposure (P for group × time=0.02 and 0.054, respectively), adjusting for growth in the first 6 months and other covariates. In contrast, infant serum APN in year 1 was not associated with the rate of weight gain in year 2. High human milk APN exposure was associated with accelerated weight trajectory during the second year of life, suggesting its role in catch-up growth after slower weight gain during the first year of life.

Insulin sensitization in Female Ob/Ob Mice by an Apo‐ Lipoprotein‐A1 Mimetic are Independent of Effects on Body Weight

Apo‐lipoprotein‐A1 mimetic, L4F, attenuates insulin resistance, abate metabolic syndrome and reduce cardio‐vascular (CV) morbidity in male obese mice. Hormonal influence on metabolic homeostasis is now well established, as such, we characterized the effects of L4F in female ob/ob vs. male ob/ob mice. Obese (ob/ob) mice were treated with L4F or vehicle daily for 6 wks, I.P. at 2mg/kg/d. Where L4F retarded weight gain in male mice (p&lt;0.05) it had no such effect in female mice. However, L4F did restore insulin tolerance (p&lt;0.05) in female mice and reduced plasma glucose (p&lt;0.05), while enhancing (p&lt;0.05) serum adiponectin levels. Also, L4F treatment in female obese mice reduced circulating levels of inflammatory cytokines (TNFα, IL‐6, IL‐1β, p&lt;0.05) and total cholesterol levels (p&lt;0.05). Metabolic homeostatic markers, such as hepatic p‐AMPK and p‐AKT levels, were enhanced (p&lt;0.05) by L4F treatment. These effects of L4F were accompanied by increased hepatic‐HO1 expression along with increased HO activity with reduced (p&lt;0.05) hepatic expression of GP91‐phox, an indicator of L4Fs attenuative effects on cellular oxidative stress. Taken together, our results show that L4F can restore metabolic homeostasis and reduce systemic inflammation in mammalian females, and because these effects are body weight independent L4F may be used in conjunction with weight loss therapy in obese patients. NIH‐ DK056601

Methadone does not alter key parameters of adult hippocampal neurogenesis in the heroin-naïve rat

Methadone is a synthetic opiate that is useful in a variety of clinical settings, including in maintenance therapy of heroin dependence and as an analgesic. However, methadone can have negative effects on cognition in humans and in rodents. The mechanisms underlying methadone-induced disruption in cognition are unknown. One possibility is that methadone disrupts adult hippocampal neurogenesis, a form of hippocampal plasticity involved in cognition that is disrupted by other opiates, like morphine. The goal of this study was to determine if methadone alters key parameters of hippocampal neurogenesis in the adult rat. Four groups of male rats were injected with saline (Saline, n=11) or methadone (Escalating, Short Term, Acute, n=10–11/group) over the course of three weeks. Weight gain, locomotor activity, and neurogenesis data were collected. Consistent with prior results, Escalating rats had slower weight gain (−4% vs. Saline). Also consistent with prior results, methadone did not alter locomotor activity over the course of a 90min test. However, closer analysis revealed that methadone – irrespective of the dose or duration – led to a decrease in locomotor activity (−11 to −20% vs. saline) when examined during the first 5min of the locomotor test. Surprisingly, methadone did not alter any of three quantified parameters relevant to adult hippocampal neurogenesis (number of Ki67-, doublecortin-, or BrdU-immunoreactive cells [BrdU given prior to saline/methadone exposure]). These results suggest that – unlike other opiates such as morphine – experimenter-delivered methadone does not alter hippocampal plasticity by decreasing the number of adult-generated neurons.

Nonspecific predictors of weight gain in the early stages of outpatient cognitive behavioral therapy for adults with anorexia nervosa: Replication and extension

This study extends previous work, examining psychological factors that influence the level of weight gain across the first 20 sessions of cognitive behavioral therapy (CBT) for anorexia nervosa. Thirty-two patients with anorexia nervosa (mean body mass index (BMI) = 16.0; SD = 1.11) completed measures of eating attitudes and comorbid axis 1 pathology at the outset of CBT, and their weight gain was measured at the 6th and 20th sessions of the therapy. Unhealthy eating attitudes at the start of therapy were associated with slower weight gain across the first 20 sessions of CBT. In contrast, higher levels of pretreatment axis 1 pathology were associated with slower weight gain only after the 6th session. The axis 1 features that moderated weight gain over 20 sessions of CBT were broader than those that had previously been shown to predict weight gain over the first 10 CBT sessions. During CBT for anorexia nervosa, weight gain might be enhanced by addressing a range of aspects of axis 1 pathology (e.g., depression, hostility, and features of anxiety). However, the approach is likely to be less important at first than directly addressing eating pathology and overvalued ideas about eating, shape, and weight.

Clinical evidence that V456A is a Cystic Fibrosis causing mutation in South Asians

BackgroundCystic Fibrosis (CF) genotypes in South Asians are variable with a decreased incidence of Delta F508 and an increased incidence of novel mutations. The objective of this study is to provide clinical evidence that V456A, a novel mutation in South Asian Cystic Fibrosis patients, can cause significant lung disease. MethodsWe extracted clinical data from a retrospective chart review of 2 CF patients of South Asian descent. ResultsPatient 1, a 10year and 11month old Pakistani female at her initial clinic visit, required multiple hospitalizations for bronchiectasis and pulmonary infections. She was pancreatic sufficient but had slow weight gain. Genetic testing revealed that she is homozygous for the CFTR V456A mutation. Patient 2, an Indian female diagnosed with CF on newborn screening, is compound heterozygous for V456A/R709X. She had slow weight gain with BMI ranging from 12.9 to 13.4kg/m2 from 3 to 5years of age and was 14.2kg/m2 at 6years of age. At 6years of age, pulmonary function tests revealed mild lung disease with FVC of 71%, FEV1 of 75%, FEF25–75 of 119%, and FEV1/FVC of 86% predicted. Sputum cultures were intermittently positive for Staphylococcus aureus and Haemophilus influenza. ConclusionsWe provide evidence that V456A can cause significant pulmonary disease in South Asian Cystic Fibrosis patients.

Calcium/Calmodulin-dependent Protein Kinase Kinase 2 Regulates Macrophage-mediated Inflammatory Responses

Calcium/calmodulin-dependent kinase kinase 2 (CaMKK2) plays a key role in regulating food intake and energy expenditure at least in part by its actions in hypothalamic neurons. Previously, we showed that loss of CaMKK2 protected mice from high-fat diet (HFD)-induced obesity and glucose intolerance. However, although pair feeding HFD to WT mice to match food consumption of CAMKK2-null mice slowed weight gain, it failed to protect from glucose intolerance. Here we show that relative to WT mice, HFD-fed CaMKK2-null mice are protected from inflammation in adipose and remain glucose-tolerant. Moreover, loss of CaMKK2 also protected mice from endotoxin shock and fulminant hepatitis. We explored the expression of CaMKK2 in immune cells and found it to be restricted to those of the monocyte/macrophage lineage. CaMKK2-null macrophages exhibited a remarkable deficiency to spread, phagocytose bacteria, and synthesize cytokines in response to the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS). Mechanistically, loss of CaMKK2 uncoupled the TLR4 cascade from activation of protein tyrosine kinase 2 (PYK2; also known as PTK2B). Our findings uncover an important function for CaMKK2 in mediating mechanisms that control the amplitude of macrophage inflammatory responses to excess nutrients or pathogen derivatives.

Low HCMV DNA Copies Can Establish Infection and Result in Significant Symptoms in Extremely Preterm Infants: A Prospective Study

Breast milk (BM) is the main source of human cytomegalovirus (HCMV) infection. We examined whether the number of HCMV DNA copies in BM is related to HCMV infection in very low birth weight (VLBW) infants. We identified 11 pairs of VLBW infants and mothers. BM samples were collected every week until 10 weeks postpartum. Urine samples were collected from the infants within 1 week, at 6 to 8 weeks, at discharge, and whenever HCMV infection was suspected. HCMV DNA in BM was positive in 7 of 11 mothers and reached a peak at 4 to 5 weeks postpartum. Of the 11, 5 infants were determined to be infected from positive HCMV DNA in the urine, despite the fact that BM was used after being frozen. Of the five, four infected infants exhibited symptoms between 35 and 60 days of age. Symptomatic infants had longer stays and slower weight gain. The HCMV infection rate is high in very preterm infants. A new strategy to prevent HCMV infection other than freezing should therefore be established.

Deletion of CaMKK2 from the Liver Lowers Blood Glucose and Improves Whole-Body Glucose Tolerance in the Mouse

Ca(2+)/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a member of the Ca(2+)/CaM-dependent protein kinase family that is expressed abundantly in brain. Previous work has revealed that CaMKK2 knockout (CaMKK2 KO) mice eat less due to a central nervous system -signaling defect and are protected from diet-induced obesity, glucose intolerance, and insulin resistance. However, here we show that pair feeding of wild-type mice to match food consumption of CAMKK2 mice slows weight gain but fails to protect from diet-induced glucose intolerance, suggesting that other alterations in CaMKK2 KO mice are responsible for their improved glucose metabolism. CaMKK2 is shown to be expressed in liver and acute, specific reduction of the kinase in the liver of high-fat diet-fed CaMKK2(floxed) mice results in lowered blood glucose and improved glucose tolerance. Primary hepatocytes isolated from CaMKK2 KO mice produce less glucose and have decreased mRNA encoding peroxisome proliferator-activated receptor γ coactivator 1-α and the gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, and these mRNA fail to respond specifically to the stimulatory effect of catecholamine in a cell-autonomous manner. The mechanism responsible for suppressed gene induction in CaMKK2 KO hepatocytes may involve diminished phosphorylation of histone deacetylase 5, an event necessary in some contexts for derepression of the peroxisome proliferator-activated receptor γ coactivator 1-α promoter. Hepatocytes from CaMKK2 KO mice also show increased rates of de novo lipogenesis and fat oxidation. The changes in fat metabolism observed correlate with steatotic liver and altered acyl carnitine metabolomic profiles in CaMKK2 KO mice. Collectively, these results are consistent with suppressed catecholamine-induced induction of gluconeogenic gene expression in CaMKK2 KO mice that leads to improved whole-body glucose homeostasis despite the presence of increased hepatic fat content.

Obesity in Preschoolers: Behavioral Correlates and Directions for Treatment

Nearly 14% of American preschoolers (ages 2-5) are obese (BMI ≥ 95th percentile for age and gender), yet this group has received little attention in the obesity intervention literature. This review examines what is known about behavioral correlates of obesity in preschoolers and the developmental context for lifestyle modification in this age group. Information was used to critically evaluate existing weight management prevention and intervention programs for preschoolers and formulate suggestions for future intervention research development. A systematic search of the medical and psychological/behavioral literatures was conducted with no date restrictions, using PubMed, PsycInfo, and MEDLINE electronic databases and bibliographies of relevant manuscripts. Evidence suggests several modifiable behaviors, such as sugar sweetened beverage intake, television use, and inadequate sleep, may differentiate obese and healthy weight preschoolers. Developmental barriers, such as food neophobia, food preferences, and tantrums challenge caregiver efforts to modify preschoolers' diet and activity and parental feeding approaches, and family routines appear related to the negative eating and activity patterns observed in obese preschoolers. Prevention programs yield modest success in slowing weight gain, but their effect on already obese preschoolers is unclear. Multi-component, family-based, behavioral interventions show initial promise in positive weight management for already obese preschoolers. Given that obesity intervention research for preschoolers is in its infancy, and the multitude of modifiable behavioral correlates for obesity in this age group, we discuss the use of an innovative and efficient research paradigm (Multiphase Optimization Strategy; MOST) to develop an optimized intervention that includes only treatment components that are found to empirically reduce obesity in preschoolers.

Choline Deficiency Attenuates Body Weight Gain and Improves Glucose Tolerance in ob/ob Mice

Previous studies demonstrated that choline supply is directly linked to high-fat-diet-induced obesity and insulin resistance in mice. The aim of this study was to evaluate if choline supply could also modulate obesity and insulin resistance caused by a genetic defect. Eight-week-old male ob/ob mice were fed for two months with either choline-deficient or choline-supplemented diet. Tissue weight including fat mass and lean mass was assessed. Intracellular signaling, plasma glucagon and insulin, and glucose and insulin tolerance tests were also investigated. The choline-deficient diet slowed body weight gain and decreased fat mass. Choline deficiency also decreased plasma glucose level and improved glucose and insulin tolerance although fatty liver was exacerbated. Increased adipose lipolytic activity, decreased plasma glucagon and reduced expression of hepatic glucagon receptor were also observed with the choline-deficient diet. Our results demonstrate that a choline-deficient diet can decrease fat mass and improve glucose tolerance in obese and diabetic mice caused by a genetic defect.

Maternal characteristics influencing birth weight and infant weight gain in the first 6 weeks post-partum: A cross-sectional study of a post-natal clinic population

Background:To investigate the relationship between certain maternal characteristic and infant birth weight and weight gain in puerperal women seen at a tertiary health centre.Materials and Methods:We measured the weight of 318, randomly selected infants after a complete physical examination at birth and at 6 weeks postnatal using standard procedures and related them to certain maternal characteristics.Results:There were 318 women and baby pairs. Maternal ages ranged from 16 to 42 years, with a mean of 25.6±1.3 years. Mean birth weight of babies was 3.10±1.89 kg; mean gestational age was 36±4.6 weeks, with 9.4% and 3.0% of babies born having low birth weight or Macrosomia respectively. Mothers from the North of the country, multiparity and systolic and/or diastolic hypertensions were factors associated with low birth weight. At 6 weeks, 27.1% of infants failed to gain weight as expected for their age. Similarly, 37.0% of infants born to mothers with some tertiary education showed slowed weight gain compared with those who had secondary (19.2%) or primary (14.7%) education, P=0.03. Maternal weight at delivery positively correlated with birth weight of the infant (r=0.357, P<0.001). However, maternal weight and blood pressure negatively correlated with infant weight gain at 6 weeks post-delivery.Conclusion:Our study demonstrates that certain maternal characteristics could play a role in the birth weight and early infant weight gain, and are preventable through simple public health approaches.

Foot-pad dermatitis in commercial broilers

In the present experiment, the presence of mycological agents in chickens with skin lesions on foot pads was investigated, in order to improve the health of broiler chickens. Foot-pad dermatitis (FPD) is described in the literature as dermatitis caused by multifactor causes. The presence of irritating chemical substances in the litter, genetic predispositions of hybrids, immune suppressive diseases of chickens, as well as the composition of commercial broiler diets that influence the occurrence of wet litter, are proven factors that contribute to a more intensive incidence of foot-pad dermatitis. Foot-pad dermatitis is a condition characterized by lesions on metatarsal and digital ventral skin of poultry feet. It is type of contact dermatitis which in severe cases shows slower weight gain, poor health condition and welfare. Taking into consideration the literature data, chickens reared in closed facilities where the bacterial and mycological agents are present partly in the litter if not properly disinfected, but also in the food or the chicken plumage, we wanted to investigate their presence in the skin of foot pads. The study was focused on incidence of foot-pad dermatitis in 500 one day old broiler chickens of Hubbard genotype, in two feeding (standard/economical) programs for broilers available on our market. Chopped straw was used as litter. At the end of fattening, all chickens were examined for the presence of lesions on the skin of the feet. Total of 39 chickens were allocated to the intensity of the lesion on foot pads rated as 2 (mild) and 3 (severe). In the mycological examination of the 9 samples of autoclaved chicken legs with lesions on the feet, we have isolated and identified the presence of fungi /mould Aspergillus fumigatus. The histopathology investigation, during which the tissue section from mild and severe skin foot pads was collected and stained using Hematoxylin and eosin, revealed the hyperkeratosis, panniculitis, ballooning degeneration and dermis inflammation. No fungal elements were observed in the sections of pads stained with Gomori methenamine silver. Birds are especially susceptible to infection with Aspergillus fumigatus. That species of fungus is also classified as allergenic factor.

Pathological changes in rat model of urinary calculus induced by melamine

To investigate melamine-induced pathological changes in the kidney. Wistar rats were fed with a diet containing 0, 1% and 2% melamine for 15 weeks. After melamine feeding was stopped, various outcome measures were observed for 4 weeks. Rats fed with melamine showed reduced caloric intake, slower weight gain and impaired renal function. The blood urea nitrogen of group A and B [(13.23 ± 5.10) mmol/L and (18.30 ± 5.90) mmol/L, respectively] and serum creatinine levels of group B [(19.90 ± 2.90) mmol/L] were higher than that of group C [(8.23 ± 2.30) mmol/L and (10.04 ± 1.73) mmol/L](P < 0.01, respectively). Additionally, the kidney coefficients of group A and B were higher than that of group C (P < 0.01, respectively). Crystals, tubular ectasia and interstitial inflammation and fibrosis were found in the kidneys of melamine fed rats. Four weeks after discontinuation of feeding with melamine-contained diet, the caloric intake and weight of the rats increased, the coefficients of the kidney decreased, and the blood urea nitrogen of group A and B [(17.96 ± 2.04) mmol/L and (19.20 ± 3.36) mmol/L, respectively] and serum creatinine levels of group B [(24.20 ± 5.28) mmol/L], which became worse than 4 weeks before (P < 0.01;P < 0.05, respectively), and were still higher than that of group C [(8.30 ± 1.79) mmol/L and (9.87 ± 2.71) mmol/L, P < 0.01, respectively]. Crystals remained inside the kidney, changes in the renal interstitium did not improve. (1) Melamine-induced urinary calculus rat model can be established by feeding 3-week old male Wistar rats with a diet containing 2% melamine for 15 weeks. The main constituent of the urinary calculus was melamine (> 90%), with a little uric acid and traces of cyanuric acid. (2) Melamine damaged the renal function, formed renal crystals, and led to the pathological changes of kidneys. All the influences seemed to be dose-depended and was related with the obstruction of the crystals or calculus in the kidney. (3) The renal function and the pathological changes did not improve 4 weeks after discontinuation of feeding with melamine-contained diet.

A Prospective Examination of Weight Gain in Hospitalized Adolescents With Anorexia Nervosa on a Recommended Refeeding Protocol

Current refeeding recommendations for adolescents hospitalized with anorexia nervosa (AN) are conservative, starting with low calories and advancing slowly to avoid refeeding syndrome. The purpose of this study was to examine weight change and clinical outcomes in hospitalized adolescents with AN on a recommended refeeding protocol. Adolescents aged 13.1-20.5 years were followed during hospitalization for AN. Weight, vital signs, electrolytes, and 24-hour fluid balance were measured daily. Percent median body mass index (%MBMI) was calculated as 50th percentile BMI for age and gender. Calories were prescribed on admission and were increased every other day. Thirty-five subjects with a mean (SD) age of 16.2 (1.9) years participated over 16.7 (6.4) days. Calories increased from 1,205 (289) to 2,668 (387). No subjects had refeeding syndrome; 20% had low serum phosphorus. Percent MBMI increased from 80.1 (11.5) to 84.5 (9.6); overall gain was 2.10 (1.98) kg. However, 83% of subjects initially lost weight. Mean %MBMI did not increase significantly until day 8. Higher calories prescribed at baseline were significantly associated with faster weight gain (p = .003) and shorter hospital stay (p = .030) in multivariate regression models adjusted for %MBMI and lowest heart rate on admission. Hospitalized adolescents with AN demonstrated initial weight loss and slow weight gain on a recommended refeeding protocol. Higher calorie diets instituted at admission predicted faster weight gain and shorter hospital stay. These findings support the development of more aggressive feeding strategies in adolescents hospitalized with AN. Further research is needed to identify caloric and supplementation regimens to maximize weight gain safely while avoiding refeeding syndrome.

Evaluation of the targeted therapy everolimus on cognitive functions and cerebral plasticity in an animal model.

e13589 Background: Cancer and treatments can induce cognitive impairments in patients, called “chemofog” such as deficits of visual and spatial memories and decline of psychomotor processing speed. Although direct effect of chemotherapy on cognitive functions and neurogenesis has been shown, the impact of targeted therapies has never been investigated. Everolimus, which blocks the mTOR pathway, alters cell proliferation, metabolism and neoangiogenesis. Gene expression in hippocampus implicated in memory processes is regulated by the mTOR signalling pathway. Thus, we used a validated behavioral animal model to test the potential cognitive troubles induced by Everolimus. In addition, ex vivo analyses were conducted on neural cell plasticity involved in hippocampus-dependent behavioral tasks. Methods: Everolimus (5 mg/kg) was daily per os administered in adult C57BL/6J Rj mice for two weeks. Learning and memory processes were evaluated 7 days after the end of the treatment period by means of the Morris water maze and the object recognition tests. Ex vivo, hippocampal neurogenesis was investigated in mice that received BrdU during the 5 last days of the treatment period. Results: Everolimus slowed body weight gain from the last day of the treatment period until the end of behavioral sessions. One week after the end of the treatment, emotional reactivity, spontaneous activity, spatial learning and memory performances, as well as behavioral flexibility and object recognition memory were not impaired by Everolimus. Ex vivo analyses of the number of neural stem cells in neurogenic area showed no modification in treated mice at the end of the period of therapy. Conclusions: At short term, Everolimus did not modify cognitive functions evaluated by means of the hippocampal- and prefrontal-dependent behavioral tasks. These observations differ from our previous studies demonstrating that chemotherapy (5-fluorouracil) led to selective long-term cognitive deficits, i.e. behavioral flexibility and recognition memory, sustained by altered neurogenesis. These results reinforce the interest of developing targeted therapies for cancer treatment.

Maternal weight gain: a determinant for fetal abdominal circumference in the second trimester

To study the association between maternal weight gain in pregnancy and fetal abdominal circumference in the second trimester. Prospective cross-sectional study. Low-risk antenatal clinic. Six hundred and fifty women with low-risk pregnancy. Women with a regular menstrual period (28±4 days) and certain information on the last menstrual period were recruited when they were referred for routine ultrasound scanning. Women with a discrepancy of>14 days between ultrasound and menstrual age were excluded. Maternal weight gain during pregnancy was derived from information in the antenatal chart and the weekly weight gain was calculated. Fetal abdominal circumference measurements were registered in gestational weeks 15-25 and their z-scores, together with the z-scores of maternal weight gain, were used in a linear regression analysis. Main outcome measures. Association between maternal weight gain and fetal abdominal circumference. Based on the complete data of 515 women we found a mean maternal weight gain during pregnancy of 0.39 kg/week and a positive association between this weight gain and fetal abdominal circumference in the second trimester (r=0.122 (95%CI 0.051-0.194)), with the strongest effect in women with the slowest weight gain (<0.28 kg/week) (r=0.554 (95%CI 0.261-0.846)). Maternal weight gain in pregnancy is related to and may determine fetal abdominal circumference in gestational weeks 15-25, particularly in those women with a slow weight gain.

Knockdown of NPY Expression in the Dorsomedial Hypothalamus Promotes Development of Brown Adipocytes and Prevents Diet-Induced Obesity

Hypothalamic neuropeptide Y (NPY) has been implicated in control of energy balance, but the physiological importance of NPY in the dorsomedial hypothalamus (DMH) remains unclear. Here we report that knockdown of NPY expression in the DMH by adeno-associated virus-mediated RNAi reduced fat depots in rats fed regular chow and ameliorated high-fat diet-induced hyperphagia and obesity. DMH NPY knockdown resulted in development of brown adipocytes in inguinal white adipose tissue through the sympathetic nervous system. This knockdown increased uncoupling protein 1 expression in both inguinal fat and interscapular brown adipose tissue (BAT). Consistent with the activation of BAT, DMH NPY knockdown increased energy expenditure and enhanced the thermogenic response to a cold environment. This knockdown also increased locomotor activity, improved glucose homeostasis, and enhanced insulin sensitivity. Together, these results demonstrate critical roles of DMH NPY in body weight regulation through affecting food intake, body adiposity, thermogenesis, energy expenditure, and physical activity.

Relationship of fruit and vegetable intake with adiposity: a systematic review

Fruit and vegetable (FV) intake has been proposed to protect against obesity. The purpose of this paper was to assess the FV consumption to adiposity relationship. Twenty-three publications were included. longitudinal or experimental designs; FV intake tested in relation to adiposity; child, adolescent or adult participants; published in English-language peer-reviewed journals. dietary pattern and cross-sectional designs; participants with health concerns. Experimental studies found increased FV consumption (in conjunction with other behaviours) contributed to reduced adiposity among overweight or obese adults, but no association was shown among children. Longitudinal studies among overweight adults found greater F and/or V consumption was associated with slower weight gain, but only half of child longitudinal studies found a significant inverse association. Limitations in methods prevented a thorough examination of the role of increased FV intake alone or mechanisms of effect. An inverse relationship between FV intake and adiposity among overweight adults appears weak; this relationship among children is unclear. Research needs to clarify the nature of, and mechanisms for, the effects of FV consumption on adiposity. Whether increases in FV intake in isolation from lower caloric intake or increased physical activity will result in declines or slower growth in adiposity remains unclear.