Accelerated Weight Gain Research Articles

Strategy for obesity prevention among school-age children (literature review)

Obesity is one of major threats to people health and life. It increases risk of many diseases, including type 2 diabetes, heart disease, arthritis, and several cancers. This is a serious problem for the Russian Federation. Half of adults in our country are considered to be overweight or obese. However, to assess objectively the prevalence of this pathology in children is very difficult. At present in Russia there is no single universally accepted system for child anthropometry. Several studies in Russian regions found that about 10% of children were overweight and obese. Main risk factors of obesity in intrauterine and perinatal periods: mother smoking during pregnancy, child accelerated weight gain during the first months of life, formula feeding and early complementary feeding. In older children main risk factors are high-calorie foods, lack of exercise and sedative behaviour. International expert community has defined preventive strategies that will support elimination of child obesity. These strategies include implementation of child development assessment system with body mass index measurement in accordance with the World Health Organization guidelines; training primary pediatricians on using this assessment system and effective obesity prevention counseling; and school-based obesity prevention programs. Physicians and teachers must understand how important obesity prevention for child health. Health and education stakeholders should actively support these preventive measures and ensure universal access to physical exercises and healthy diet in schools. Alfa-Endo Program will assist all these initiatives.

Mild endothelial dysfunction in Sirt3 knockout mice fed a high-cholesterol diet: protective role of a novel C/EBP-β-dependent feedback regulation of SOD2.

Sirtuin 3 (Sirt3) is an NAD+-dependent mitochondrial deacetylase associated with superoxide dismutase 2 (SOD2)-mediated protection from oxidative stress. We have reported accelerated weight gain and impaired metabolic flexibility in atherosclerotic Sirt3−/− mice. Oxidative stress is a hallmark of endothelial dysfunction. Yet, the role of Sirt3 in this context remains unknown. Thus, we aimed to unravel the effects of endogenous Sirt3 on endothelial function and oxidative stress. Knockdown of Sirt3 in human aortic endothelial cells (HAEC) increased intracellular mitochondrial superoxide accumulation, as assessed by electron spin resonance spectroscopy and fluorescence imaging. Endothelium-dependent relaxation of aortic rings from Sirt3−/− mice exposed to a normal diet did not differ from wild-type controls. However, following 12 weeks of high-cholesterol diet and increasing oxidative stress, endothelial function of Sirt3−/− mice was mildly impaired compared with wild-type controls. Relaxation was restored upon enhanced superoxide scavenging using pegylated superoxide dismutase. Knockdown of Sirt3 in cultured HAEC diminished SOD2 specific activity, which was compensated for by a CCAAT/enhancer binding protein beta (C/EBP-β)-dependent transcriptional induction of SOD2. Abrogation of this feedback regulation by simultaneous knockdown of C/EBP-β and Sirt3 exacerbated mitochondrial superoxide accumulation and culminated into endothelial cell death upon prolonged culture. Taken together, Sirt3 deficiency induces a mild, superoxide-dependent endothelial dysfunction in mice fed a high-cholesterol diet. In cultured endothelial cells, a novel C/EBP-β-dependent rescue mechanism maintains net SOD2 activity upon transient knockdown of Sirt3.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-016-0552-7) contains supplementary material, which is available to authorized users.

Polygenic Risk, Appetite Traits, and Weight Gain in Middle Childhood: A Longitudinal Study.

Genome-wide association studies have identified genetic risks for obesity. These genetic risks influence development of obesity partly by accelerating weight gain in childhood. Research is needed to identify mechanisms to inform intervention. Cross-sectional studies suggest appetite traits as a candidate mechanism. Longitudinal studies are needed to test whether appetite traits mediate genetic influences on children's weight gain. To test whether genetic risk for obesity predicts accelerated weight gain in middle childhood (ages 4-8 years) and whether genetic association with accelerated weight gain is mediated by appetite traits. Longitudinal study of a representative birth cohort at the Trondheim Early Secure Study, Trondheim, Norway, enrolled at age 4 years during 2007 to 2008, with follow-ups at ages 6 and 8 years. Participants were sampled from all children born in 2003 or 2004 who attended regular community health checkups for 4-year-olds (97.2% attendance; 82.0% consent rate, n = 2475). Nine hundred ninety-five children participated at age 4 years, 795 at age 6 years, and 699 at age 8 years. Analyses included 652 children with genotype, adiposity, and appetite data. Outcomes were body mass index and body-fat phenotypes measured from anthropometry (ages 4, 6, and 8 years) and bioelectrical impedance (ages 6 and 8 years). Genetic risk for obesity was measured using a genetic risk score composed of 32 single-nucleotide polymorphisms previously discovered in genome-wide association studies of adult body mass index. Appetite traits were measured at age 6 years with the Children's Eating Behavior Questionnaire. Of the 652 genotyped child participants, 323 (49.5%) were female, 58 (8.9%) were overweight, and 1 (0.2%) was obese. Children at higher genetic risk for obesity had higher baseline body mass index and fat mass compared with lower genetic risk peers, and they gained weight and fat mass more rapidly during follow-up. Each SD increase in genetic risk score was associated with a 0.22-point increase in BMI at age-4 baseline (for the intercept, unstandardized path coefficient B = 0.22 [95% CI, 0.06-0.38]; P = .008. Children with higher genetic risk scores also gained BMI points more rapidly from ages 4 to 6 years (B = 0.11 [95% CI, 0.03-0.20]; P = .01 ; β = 0.12) and from 6 to 8 years (B = 0.09 [95% CI, 0.00-0.19]; P = .05; β = 0.10), compared with their lower genetic risk peers. Children at higher genetic risk had higher levels of alleged obesogenic appetite traits than peers with lower genetic risk at age 6 years, but appetite traits did not mediate genetic associations with weight gain. The sum of the 5 indirect effects was B = -0.001 (95% CI, -0.02 -0.01); P = .86; β = 0.00. Genetic risk for obesity is associated with accelerated childhood weight gain. Interventions targeting childhood weight gain may provide one path to mitigating genetic risk. However, middle childhood appetite traits may not be a promising target for such interventions. Studies of early-childhood samples are needed to test whether appetite traits explain how genetic risks accelerate growth earlier in development.

Postnatal High Protein Intake Can Contribute to Accelerated Weight Gain of Infants and Increased Obesity Risk.

Worldwide, 38% of women are now overweight (BMI 25-30) or obese (BMI ≥30). There is increasing evidence that maternal obesity can result in unfavorable (epigenetic) pre- and postnatal programming of important genes of the offspring. Infants of overweight mothers show faster weight gain during infancy, which is associated with higher risk of obesity during childhood and adult life. This can have lifelong consequences such as increased risk of noncommunicable diseases. Many studies indicate that infants of obese and nonobese mothers who were fed traditional (high-protein) formulas gain more rapidly weight than breastfed infants. An updated meta-analysis (n = 1,150) indicates that infants from four continents who were fed a whey-based, low-protein (1.8 g/100 kcal) formula with an essential amino-acid profile closer to breast milk grow in accordance with the World Health Organization (WHO) growth standard (0-4 months). A new experimental low-protein (1.61-1.65 g protein/100 kcal) formula for infants between 3 and 12 months of age was recently tested in two randomized clinical trials. One trial in the general US population indicates lower weight between 4 and 12 months of age in infants fed the low-protein formula when compared to infants on the high-protein formula (p = 0.031). Weight gain was not inferior to the WHO growth standards. Longitudinal analysis of odds ratios from 4 to 12 months of age showed a lower incidence of infants with weight >85th percentile in the low-protein group compared with the high-protein group (p = 0.015). In the second trial, which was conducted in Chile and included infants of mothers with BMI >25, infants fed the low-protein formula gained less weight between 4 and 12 months (p = 0.022) and until 24 months (p = 0.031) than the high-protein group. Weight gain was similar to the breastfed reference group. In both trials, biomarkers of protein metabolism (insulin-like growth factor-1 and C-peptide) of the low-protein groups were closer to breastfed infants than the respective biomarkers of the high-protein groups. Health economic analyses indicate that feeding low-protein formulas to nonbreastfed infants would result in cost savings for both the individual and the society. Preventive measures against childhood and adult obesity should include promotion of breastfeeding for 6 months or longer, and use of low-protein formulas in nonbreastfed infants.

Correction: Brief Parenteral Nutrition Accelerates Weight Gain, Head Growth Even in Healthy VLBWs

There is an error in the third-to-last sentence of the “Design, Setting, and Participants” subsection in the Methods. The correct sentence is: We further excluded infants who died before discharge (n = 39), infants discharged after 48 weeks corrected age (n = 348); infants who developed NEC (n = 13) or underwent surgery (n = 385); and infants missing growth data (n = 178). In Fig 1, the second box of the flow chart contains incorrect information. “600” should be “3279.” Please see the corrected Fig 1 here. Fig 1 Population Flow Chart In Fig 2, the axis labels are missing from both panels. Please see the corrected Fig 2 here. Fig 2 Comparison of nutritional practices in 75 institutions in Japan. In Fig 4, there are errors in the axis labels for all three panels. “n = 2677 non-SGA infants” should be “n = 2662 non-SGA infants” and “n = 4006 All infants” should be “n = 4005 All infants.” Fig 4 Estimated effect of administering parenteral nutrition. There are a number of errors in Table 1. Please see the complete, correct Table 1 here. Table 1 Maternal and infant characteristics of 4,005 very low birth weight infants of 24–32 weeks’ of gestation who reached full enteral feeding within 2 weeks.

Short-term variability in body weight predicts long-term weight gain

Body weight in lower animals and humans is highly stable despite a very large flux in energy intake and expenditure over time. Conversely, the existence of higher-than-average variability in weight may indicate a disruption in the mechanisms responsible for homeostatic weight regulation. In a sample chosen for weight-gain proneness, we evaluated whether weight variability over a 6-mo period predicted subsequent weight change from 6 to 24 mo. A total of 171 nonobese women were recruited to participate in this longitudinal study in which weight was measured 4 times over 24 mo. The initial 3 weights were used to calculate weight variability with the use of a root mean square error approach to assess fluctuations in weight independent of trajectory. Linear regression analysis was used to examine whether weight variability in the initial 6 mo predicted weight change 18 mo later. Greater weight variability significantly predicted amount of weight gained. This result was unchanged after control for baseline body mass index (BMI) and BMI change from baseline to 6 mo and for measures of disinhibition, restrained eating, and dieting. Elevated weight variability in young women may signal the degradation of body weight regulatory systems. In an obesogenic environment this may eventuate in accelerated weight gain, particularly in those with a genetic susceptibility toward overweight. Future research is needed to evaluate the reliability of weight variability as a predictor of future weight gain and the sources of its predictive effect. The trial on which this study is based is registered at clinicaltrials.gov as NCT00456131.

Overweight patterns throughout childhood and cardiometabolic markers in early adolescence.

Risk of cardiovascular and metabolic disease is higher in adults who were relatively thin at birth and had subsequent accelerated weight gain. This specific pattern of weight gain may relate to unfavorable cardiometabolic markers already in childhood. We prospectively assessed whether children with different patterns of overweight development from age 3 months to 11 years had distinct levels of cardiometabolic markers at age 12 years. We used data of 1500 children participating in the PIAMA birth cohort that started in 1996/1997. Parents reported height and weight during 10 waves of follow-up from age 3 months to 11 years. Four distinct overweight development patterns were derived using longitudinal latent class analysis; 'never'; 'early transient'; 'gradually developing' and 'persistent' overweight. Cardiometabolic markers (total-to-high-density lipoprotein cholesterol (TC/HDLC) ratio, blood pressure (BP), glycated hemoglobin (HbA1c)) were assessed at age 12 years in 1500 children. Children who developed overweight gradually and children with persistent overweight throughout childhood, at age 12 years had a 2-3-fold higher risk of having high (>90th centile) TC/HDLC ratio, systolic and diastolic BP, compared with children who were never overweight. In children who gradually developed overweight, TC/HDLC ratio was 0.75 higher (95% confidence interval (CI) 0.54-0.96); systolic BP 4.90 mmHg higher (95% CI 2.45-7.36) and diastolic BP 1.78 mmHg higher (95% CI 0.07-3.49) than in children who never had overweight. Estimates for children with persistent overweight were similar. Children with gradually developing overweight, and those with persistent overweight had unfavorable cholesterol and blood pressure levels already at age 12 years, whereas children with early transient overweight avoided these unfavorable outcomes. Our results support the hypothesis that specific overweight patterns predispose to an adverse cardiometabolic profile, which is already apparent in early adolescence before progressing to adult cardiometabolic disease.

Late prematurity and adiposity in adolescents: Evidence from "Children of 1997" birth cohort.

The association of late prematurity with later adiposity is unclear, and the mediating role of infant growth is seldom studied. We assessed the association of late prematurity with markers of adiposity in adolescence and tested whether accelerated infant weight gain mediated the association. In the Chinese birth cohort "Children of 1997," we used multivariable linear regression to assess the adjusted association of late premature (n = 295), compared to term (n = 6874), births with markers of adiposity at 14 years. We tested whether any association was mediated by accelerated weight gain from birth to 12 months, i.e., a change in weight z-score ≥0.67. Late premature births had greater body mass index (BMI) z-score (0.21, 95% confidence interval (CI) 0.07, 0.35), waist-hip ratio z-score (0.16, 95% CI 0.03, 0.29), and waist-height ratio z-score (0.27, 95% CI 0.14, 0.40) than term births in adolescence. The association of late prematurity with higher adolescent BMI, but not waist ratios, was mediated by accelerated infant weight gain. Late prematurity was associated with higher BMI and waist ratios in adolescence, but only the association with BMI was mediated by infant weight gain, suggesting vulnerability to metabolic risk in late premature births may arise through multiple pathways.

Risk for Nonalcoholic Fatty Liver Disease in Young Adults Born Preterm

Background: Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Accelerated catch-up in weight during infancy in subjects born at full term has been associated with increased risk for NAFLD in adulthood, but this association has not been studied in subjects born preterm. Methods: In 162 young adults born at a gestational age <36 weeks, we assessed the associations between fatty liver index (FLI, 0-100) and birth weight standard deviation score and first-year weight gain. We performed comparisons between subjects with and without accelerated catch-up in weight in the first year after term age. An FLI score was assigned to each participant to determine the clinical relevance, and regression analyses were performed. Results: Accelerated weight gain in the first 3 months after term age was associated with FLI as a continuous variable, whereas gestational age and low birth weight were not. Of the subjects with accelerated catch-up in weight-for-length after term age, 7.3% had a high FLI at the age of 21 years, whereas none of the subjects without accelerated catch-up in weight had a high FLI. Conclusion: Our study shows that accelerated weight gain after term age is associated with an increased risk of developing NAFLD in young adults born preterm.

Early Second Trimester Weight Gain in Obese Women Predicts Excessive Gestational Weight Gain in Pregnancy.

To assess gestational weight gain (GWG) in obese women to determine an inflection point that identifies women at risk for excessive weight gain. This is an observational prospective cohort study of pregnancies managed through the UC San Diego Maternal Weight and Wellness Program from 2011 to 2014. The primary outcome was total gestational weight gain. GWG was categorized as inadequate (<11 pounds), adequate (11-20 pounds), and excessive (>20 pounds) based on Institute of Medicine (IOM) recommendations. Other outcomes were GWG by trimester and postpartum weight retention. Bivariate and multivariate analyses were used to assess factors associated with GWG. Ninety-five patients had a mean prepregnancy body mass index (BMI) of 41.9 ± 8.9 kg/m(2) and a net weight gain of 21.9 ± 19 pounds. First trimester GWG was -0.3 ± 4.9 pounds, second trimester was 10.4 ± 10.8 pounds, and third trimester was 11.4 ± 8.5 pounds for all participants. Women who exceeded IOM recommendations accelerated weight gain at 12-14 weeks and gained a majority of weight during the second trimester. Weight gain of more than two pounds at 12-14 weeks had a 96 % positive predictive value (95 % CI 79-99) for excessive GWG. Postpartum women with excessive GWG retained more weight than those with inadequate GWG (10.7 ± 15.6 pounds compared with -13.6 ± 10.9 pounds, P < 0.001). On multiple linear regression GWG by trimester was predictive of total GWG with second and third trimester GWG having the greatest effect on total GWG. Prepregnancy BMI and gestational diabetes were not predictors of total GWG. Obese women at risk for excessive GWG may be identified as early as 12-14 weeks and gain most weight during the second trimester. GWG less than 11 pounds resulted in significant postpartum weight loss among obese women.

Effectiveness of developmentally supportive care on improving the growth and development of preemy

Objective To observe and explore the clinical value of developmentally supportive care (DSC) to improve the growth and development for preemy. Methods A total of 86 preterm children in this hospital since March 2013 to September 2014 were selected, and were randomized divided into two groups, 43 cases in the intervention group and 43 cases in the control group. The patients of intervention group received DSC nursing model, while the patients of control group received routine nursing. Calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) levels, bone mineral density (BMD) as well as body weight had been measured and compared at birth, 1 month, 3 months and 6 months after born in the two groups. Results After 1 month intervention, the body wight of intervention group was (1 838.2±297.3) g higher than (1 463.4±189.4) g comparative control group (t=5.209, P<0.01). After 3 months intervention in the intervention group, the blood Ca (4.92±1.26) mmol/L, blood P (2.53±0.28) mmol/L were above those of control group, but ALP (298.3±27.4) U/L was under that of control group (t=6.165, 10.500, 6.915; P<0.05). The BMD of intervention group was (0.34±0.06)g/m2 and (0.24±0.02)g/m2 in the control group 6 months after born with statistical significance between two groups (t=5.762, P<0.01). Conclusions DSC model can effectively improve preemy the nutrition, improve and accelerate weight gain, thereby can help the growth and development of preterm children. Key words: Developmentally supportive care; Preemy; Bmineral density; Alkaline phosphatase

Patterns of Weight Gain in Middle-Aged and Older US Adults, 1992–2010

Cross-sectional analyses of national data have found that persons with high baseline body mass index (BMI) gain weight faster than persons at the median and that those whose weight was below the median gain very little weight. However, it is not clear whether these population-level changes reflect patterns at the individual level. We examined longitudinal changes in BMI in initially underweight, normal-weight, overweight, and obese US men and women using individual-level repeat data from the Health and Retirement Study (n = 15,895; age range, 40-69 years at baseline). Linear mixed-effect regression was used to model 6-year change in self-reported BMI during 4 study periods (1992/1994-1998/2000, 1996/1998-2002/2004, 2000/2002-2006/2008, and 2004-2010). In the first 6-year period, the mean increase in BMI was greatest among persons who were initially normal weight (0.3 kg/m [95% confidence interval = 0.2 to 0.4]) and overweight (0.2 kg/m [0.1 to 0.3]). Weight gain accelerated in these groups with each subsequent period. Weight gain was less for initially class-I obese participants, and a net decrease in BMI was observed for class-III obese participants. These analyses suggest that the change in mean BMI among middle-aged and older US adults between 1992 and 2010 resulted mainly from accelerated weight gain among persons who were initially normal weight and overweight.

Neonatal overfeeding attenuates acute central pro-inflammatory effects of short-term high fat diet.

Neonatal obesity predisposes individuals to obesity throughout life. In rats, neonatal overfeeding also leads to early accelerated weight gain that persists into adulthood. The phenotype is associated with dysfunction in a number of systems including paraventricular nucleus of the hypothalamus (PVN) responses to psychological and immune stressors. However, in many cases weight gain in neonatally overfed rats stabilizes in early adulthood so the animal does not become more obese as it ages. Here we examined if neonatal overfeeding by suckling rats in small litters predisposes them to exacerbated metabolic and central inflammatory disturbances if they are also given a high fat diet in later life. In adulthood we gave the rats normal chow, 3 days, or 3 weeks high fat diet (45% kcal from fat) and measured peripheral indices of metabolic disturbance. We also investigated hypothalamic microglial changes, as an index of central inflammation, as well as PVN responses to lipopolysaccharide (LPS). Surprisingly, neonatal overfeeding did not predispose rats to the metabolic effects of a high fat diet. Weight changes and glucose metabolism were unaffected by the early life experience. However, short term (3 day) high fat diet was associated with more microglia in the hypothalamus and a markedly exacerbated PVN response to LPS in control rats; effects not seen in the neonatally overfed. Our findings indicate neonatally overfed animals are not more susceptible to the adverse metabolic effects of a short-term high fat diet but may be less able to respond to the central effects.

Loss of Atg12, but not Atg5, in pro-opiomelanocortin neurons exacerbates diet-induced obesity

The autophagy-related proteins ATG12 and ATG5 form a covalent complex essential for autophagy. Here, we demonstrate that ATG12 has distinct functions from ATG5 in pro-opiomelanocortin (POMC)-expressing neurons. Upon high-fat diet (HFD) consumption, mice lacking Atg12 in POMC-positive neurons exhibit accelerated weight gain, adiposity, and glucose intolerance, which is associated with increased food intake, reduced ambulation, and decreased LEP/leptin sensitivity. Importantly, although genetic deletion of either Atg12 or Atg5 renders POMC neurons autophagy-deficient, mice lacking Atg5 in POMC neurons do not exhibit these phenotypes. Hence, we propose nonautophagic functions for ATG12 in POMC neurons that counteract excessive weight gain in response to HFD consumption.

Selective Association between Cephalosporin, Quinolone, Macrolide, and Penicillin Antibiotic Consumption and Childhood Obesity in Europe

The accelerated weight gain in productive animals as a result of feeding antibiotic enriched fodder has been well known for decades. The better energy harvest is the result of modified gut microbiota as a consequence of applied antibiotics. Similar mechanisms might result obesity in humans as well. Objectives: Finding associations between global antibiotic consumption of different classes in EU countries and obesity data in adults and children prove that antibiotics might play a significant role in the development of obesity “epidemics” and related illnesses. Methods: Antibiotic consumption data were compared with obesity figures in adults and children in European countries and statistically analyzed for significance. Results: Significant correlation was found between the average yearly consumption of cephalosporins (p = 0.007), quinolones (p = 0.031), macrolides (p = 0.000083) and childhood obesity data, but no significant association was observed with the average penicillin consumption. No association was observed between adult obesity and any of the antibiotic classes studied. Conclusions: Our results support the hypothesis that different types of antibiotics might influence the development of obesity among children, and this finding can serve as a unified explanation for the development of obesity “epidemics”, similarly to the obesity and gut flora alteration-related diseases (type 2 diabetes mellitus, autism, etc.).

Piecewise Mixed Effects Model to Compare the Weight-gain Patter ns Before and After Diagnosis of Asthma in Children Younger than 5 Years.

Asthma and obesity are two significant public health problems that both originate in early childhood and have shared risk factors and manifestations. Studies suggest a strong association between asthma development and subsequent accelerated weight gain. Children are diagnosed with asthma in early childhood and are often exposed to factors associated with rapid weight gain. This article intends to demonstrate an innovative application of the piecewise mixed effects model to characterize the difference in the temporal rate of change in BMIz, the standardized scores of body mass index and weight-for-length that measure weight status, before and after asthma diagnosis in children younger than 5 years. The data consist of unique sequences from 1194 children's clinic visits during the first 5 years of life. We used a knot at the time of diagnosis and detected a differential weight-gain pattern before and after asthma diagnosis. The pre- and post-asthma-diagnosis weight-gain patterns further differ by sex and race-ethnicity. After asthma diagnosis, female children showed a higher increase in the rate of change in BMIz than males. Non-Hispanic African Americans and Hispanics had higher post-diagnosis rates of change in BMIz than Caucasians. The differential weight-gain patterns between male and female children were mainly contributed by Caucasian children. These findings could have important implications in the clinical care of children after asthma diagnosis.

Evaluation of BMI in obese adolescents at weight-loss camp with the Boy Scouts of America

Abstract Background: Summertime is particularly problematic for obese youth, as this unstructured time typically shows accelerated weight gain. We hypothesized that obese adolescents participating in a pilot summer camp

Determination of illegal antimicrobials in aquaculture feed and fish: An ELISA study

Antimicrobials are added to the feed or drinking water of food-producing animals to reduce susceptibility to infection, accelerate weight gain, or reduce the amount of food required to gain weight. Some compounds have been banned for food safety reasons, for other agents the U.S. Food and Drug Administration (FDA) is implementing a plan with industry to phase out a number of antibiotics.The concentrations of crystal violet (CRY), chloramphenicol (CAP), gentamicin (GEN), fluoroquinolone-enrofloxacin (FQ), malachite green (MG), and the metabolites of furaltadone (FU) and furazolidone (FZ) antibiotics (respectively AMOZ and AOZ) were determined in 30 samples both feed and fish from an aquaculture farm in eastern Sicily (Italy) using commercial ELISA Kits. Levels exceeding the method's detection capability were found in all feed and tissue samples. Feed contained all the analytes tested; GEN, CRY and CAP showed the highest mean concentrations, respectively 31.8, 4.05 and 3.67 μg kg−1. The mean concentrations of CAP, CRY, FQ, MG, AMOZ and AOZ in muscle were 0.57, 2.05, 0.14, 0.48, 0.29 and 0.09 μg kg−1, respectively (the assay was not certified to determine GEN in muscle). The higher levels detected in feed are explained by the fact that 50% of farmed fish is used to make fish meal, thus compounding bio-accumulation. Our data show that aquaculture feed and fish contain banned antimicrobials. Consumption of farmed fish may therefore involve a risk for consumers, besides contributing to the growth of antibacterial resistance. Surveys of larger feed and fish samples are needed to achieve a more reliable assessment of consumer risk.

Intestinal alkaline phosphatase deficiency leads to lipopolysaccharide desensitization and faster weight gain.

Animals develop in the presence of complex microbial communities, and early host responses to these microbes can influence key aspects of development, such as maturation of the immune system, in ways that impact adult physiology. We previously showed that the zebrafish intestinal alkaline phosphatase (ALPI) gene alpi.1 was induced by Gram-negative bacterium-derived lipopolysaccharide (LPS), a process dependent on myeloid differentiation primary response gene 88 (MYD88), and functioned to detoxify LPS and prevent excessive host inflammatory responses to commensal microbiota in the newly colonized intestine. In the present study, we examined whether the regulation and function of ALPI were conserved in mammals. We found that among the mouse ALPI genes, Akp3 was specifically upregulated by the microbiota, but through a mechanism independent of LPS or MYD88. We showed that disruption of Akp3 did not significantly affect intestinal inflammatory responses to commensal microbiota or animal susceptibility to Yersinia pseudotuberculosis infection. However, we found that Akp3(-/-) mice acquired LPS tolerance during postweaning development, suggesting that Akp3 plays an important role in immune education. Finally, we demonstrated that inhibiting LPS sensing with a mutation in CD14 abrogated the accelerated weight gain in Akp3(-/-) mice receiving a high-fat diet, suggesting that the weight gain is caused by excessive LPS in Akp3(-/-) mice.

Sodium-glucose cotransport inhibitors: mechanisms, metabolic effects and implications for the treatment of diabetic patients with chronic kidney disease.

Remarkable progress has been achieved in the field of diabetes with the development of incretin analogues, dipeptidyl peptidase IV inhibitors and novel insulin analogues; nevertheless, there is an unmet need for additional therapeutic options. Individualization of HbA1c target levels is a recent progress within the field. Approximately 50% of diabetics do not reach a previously aspired treatment goal of glycosylated HbA1 levels below 7% and often face a vicious circle with accelerated weight gain. Current antidiabetic therapeutics mainly target the decline in insulin secretion and ameliorate insulin resistance. In this regard a new generation of drugs, denoted gliflozines, that specifically interfere with sodium-glucose cotransporters (SGLT)-2 and exhibit a favourable impact on glucose metabolism in patients with type 2 diabetes are emerging as hopeful avenues. The resultant negative energy balance caused by glucosuria results in long-term weight losses, significantly reduced HbA1c levels approximating 0.5-1.0% and may in addition exert beneficial effects on blood pressure, reactive oxygen products and inflammatory mediators. Recent studies indicate improvement in β-cell glucose sensitivity and insulin sensitivity in patients treated with gliflozines, a decrease in tissue glucose disposal and interestingly an increase in endogenous glucose production. The list of side effects observed under SGLT2 inhibition includes increased rates of genitourinary infections, balanitis, vulvovaginitis, hypotensive episodes and acute deterioration of kidney function. Main questions towards the safety profile are still unanswered given that long-term clinical outcome data with SGLT2 inhibition are lacking and the cardiovascular safety profile is under scrutiny in large trials. Thus, the successful development of selective SGLT2 inhibitors for therapeutic use in diabetics has a huge potential to meet patients' needs. However, it awaits quick results from clinical trials with meaningful clinical endpoints.