Promote Weight Gain Research Articles

THE EFFECT OF ELECTROLYTES AND ENERGY DRINKS CONSUMPTION ON ATHLETIC PERFORMANCE – A NARRATIVE REVIEW

The major aim of the current narrative review was to present the current scientific knowledge on the potential effect of electrolytes and energy drink consumption on athletic performance and make recommendations for safe consumption. Athletes appreciate the need to consume fluids before, during, and after exercise as well as the significance of hydration by using drinks or/and energy drinks containing carbohydrates, salts, caffeine, taurine, and other ingredients. Energy drinks are considered by many athletes and/or exercisers to promote, in addition to high levels of energy, important hydration during exercise. The high levels of temperature and humidity in the atmosphere combined with intense exercise of the athlete increases the fluid requirements to avoid a possible risk of thermal disturbances. It is recommended that at least 4 hours before the start of the sports effort, the athlete should consume 5-7 ml of fluids per kilogram of body weight. During exercise that lasts more than 40 minutes, the creation of personalized hydration strategies is proposed. The athlete should try to drink fluids to replace, at least to some extent, enough of the fluid lost through sweat so that the total fluid deficit for a training session or competition is kept at no more than approximately 2% of body mass (an average of 200 ml per 20 min of exercise). During exercise lasting more than 1 hour and causing fatigue, athletes are advised to consume a carbohydrate source that is rapidly converted to blood glucose, while, sodium should be included in fluids consumed during exercise lasting more than 1-2 hours. The main ergogenic nutrients in most energy drinks appear to be carbohydrates and/or caffeine and taurine. The ergogenic value of caffeine on mental and physical performance is well established. Consuming energy drinks 10-60 minutes before exercise can improve focus, alertness, anaerobic performance, and/or aerobic exercise performance. Higher calorie energy drink intake may promote weight gain if the energy intake from its consumption is not carefully assessed as part of total daily energy intake. Children and adolescents should consider using energy drinks only with parental consent and after considering the number of carbohydrates, caffeine, and other nutrients contained in energy drinks.<p> </p><p><strong> Article visualizations:</strong></p><p><img src="/-counters-/edu_01/0333/a.php" alt="Hit counter" /></p>

Menus prescribed for diabetes management by Malawian referral hospitals are loaded with calories from carbohydrates and may worsen diabetes condition.

Background: Management of diabetes demands reduction of carbohydrates and moderation of total calories, fats and protein to promote weight loss while controlling postprandial blood glucose. Hospitals prescribe menus to diabetic patients to achieve these reasons. Whether these menus provide meals that help improve diabetes outcome remains unknown. Aim: Therefore, this study assessed six menus from six different referral hospitals in Malawi. Method: We formulated three separate diets (n = 3) encompassing breakfast, 10 am snack, lunch, 3 pm snack and super that a diabetic person would consume in a day as prescribed by each menu. We developed nutritionally adequate meals based on foods listed on the menu. We calculated, using the Malawi Food Composition Table (MFCT), total available carbohydrates, energy, protein, total fats, SAFA, MUFA and PUFA that each diet provides. We averaged the nutrient content from the three diets. Results: Menus from QECH and ST Joseph Mission Hospital provide significantly higher total carbohydrates (p = 0.001), total energy (p = 0.000) and fats (p = 0.01) but contain similar proteins (p = 0.761). The proportion of energy from carbohydrates for all the menus is very high and ranges from 68-81% while protein and fat proportions are lower and range from 7-16% and 7-20%, respectively. Conclusion: These menus have high propensity to increase postprandial blood glucose and promote weight gain that could be harmful to a diabetic person. All the menus deviate from a somehow recommended energy contribution of approximately 50:25:25 from carbohydrates, fat and protein, respectively.

Alternate-day fasting, a high-sucrose/caloric diet and praziquantel treatment influence biochemical and behavioral parameters during Schistosoma mansoni infection in male BALB/c mice

Schistosoma mansoni-induced granulomas result in severe damage to the host's liver, as well as neurological and metabolic disorders. We evaluated the biochemical and behavioral changes during schistosomiasis under three diet protocols: ad libitum (AL), alternate-day fasting (ADF) and a high-sucrose/caloric diet (HSD). Healthy male BALB/c mice were divided into noninfected, matched infected and infected/treated [praziquantel (PZQ)] groups. Caloric intake and energy efficiency coefficients associated with diets were measured. Behavioral (exploratory and locomotor) and biochemical (glucose, triglycerides, total cholesterol, AST, ALT, ALP, and γ-GT) tests and histological analysis were performed. Fifteen weeks postinfection, HSD and PZQ promoted weight gain, with higher caloric consumption than ADF (p < 0.05), reflecting serum glucose levels and lipid profiles. HSD and PZQ prevented liver dysfunction (AST and ALT) and significantly prevented increases in granuloma area (p < 0.05). HSD and PZQ also significantly improved mouse physical performance in exploratory and locomotor behavior (p < 0.05), reversing the impaired motivation caused by infection. These findings showed that ADF worsened the course of S. mansoni infection, while HSD and PZQ, even with synergistic effects, prevented and/or attenuated biochemical and behavioral impairment from infection.

Obesity and COVID-19 in Children and Adolescents: Reciprocal Detrimental Influence-Systematic Literature Review and Meta-Analysis.

The dramatic lifestyle changes forced by COVID-19-related lockdown promoted weight gain, with a stronger impact on obese subjects, at higher risk of severe infection. The PubMed database was searched to identify original studies assessing: (1) the extent and risk factors of lockdown-induced weight increase; and (2) the impact of obesity on the risk of hospital admission in children and adolescents. A systematic literature review and meta-analyses were performed. Twenty out of 13,986 identified records were included. A significant weight increase was reported in the majority of subjects, with no apparent gender or age differences. It was induced by a higher consumption of hypercaloric/hyperglycemic/junk food and/or the reduction of physical activity, often associated with an altered sleep–wake cycle. On the other hand, obesity increased the risk of hospitalization (OR = 4.38; 95% C.I. 1.46–13.19; p = 0.009; I2 = 96%) as compared to the normal weight population. COVID-19 and obesity represent epidemic conditions with reciprocal detrimental impact. Urgent public health interventions, targeting the various age and social strata, and involving governmental authorities, health care personnel, teachers and families are warranted to increase awareness and actively promote healthy lifestyles to contrast pediatric obesity and its detrimental consequences at a global level.

Curcuminoids for Metabolic Syndrome: Meta-Analysis Evidences Toward Personalized Prevention and Treatment Management.

The metabolic syndrome (MS) is a multifactorial syndrome associated with a significant economic burden and healthcare costs. MS management often requires multiple treatments (polydrug) to ameliorate conditions such as diabetes mellitus, insulin resistance, obesity, cardiovascular diseases, hypertension, and non-alcoholic fatty liver disease (NAFLD). However, various therapeutics and possible drug-drug interactions may also increase the risk of MS by altering lipid and glucose metabolism and promoting weight gain. In addition, the medications cause side effects such as nausea, flatulence, bloating, insomnia, restlessness, asthenia, palpitations, cardiac arrhythmias, dizziness, and blurred vision. Therefore, is important to identify and develop new safe and effective agents based on a multi-target approach to treat and manage MS. Natural products, such as curcumin, have multi-modalities to simultaneously target several factors involved in the development of MS. This review discusses the recent preclinical and clinical findings, and up-to-date meta-analysis from Randomized Controlled Trials regarding the effects of curcumin on MS, as well as the metabonomics and a pharma-metabolomics outlook considering curcumin metabolites, the gut microbiome, and environment for a complementary personalized prevention and treatment for MS management.

Plant-Based Oral Nutrition Supplementation Promotes Weight Gain in Patient Status-Post Burn Injury

ObjectivesBurn nutrition therapy is intended to mitigate some but not all the catabolism of lean body mass seen in severe burn patients. Hypermetabolism is a chronic problem and can last 2–3 years after injury. Vegetarian and non-vegetarian diets have been found to be comparable in the outcomes and nutritional status of patients 60 days post burn.MethodsThis case report documents a hypermetabolic burn patient's transition to an oral diet with use of a plant-based pea protein enteral formula (PPEF) for maintenance of weight and nutritional status. Patient was a 52 year old male with no significant past medical history who presented with 55% total body surface area burn, admitted to the burn ICU on 1/2/21. Patient was placed on a dairy-based immunomodulating formula as exclusive enteral nutrition with an additional protein modular upon admission. On 2/23/21, patient was transitioned to a regular, vegetarian diet, per patient dietary preference, with supplemental enteral nutrition (EN) and able to meet 12% of calorie needs orally (PO). A standard, intact PPEF oral nutrition supplement (ONS) was added three times daily on 2/25/21. On 3/8/21, EN was held to allow for appetite stimulation. Patient consumed minimal amounts PO and only 1–2 ONS per day, therefore, the dietitian changed the ONS to a standard, intact calorically dense PPEF. Patient consumed 2–4 calorically dense PPEF ONS per day for the next 7 weeks until discharge. This accounted for 32–82.5% of patient's total calorie needs and 23.3–65.5% of total protein needs while on oral diet.ResultsDuring hospitalization, the patient gained 5.3kg while on oral diet and PPEF ONS. Patient was then discharged (d/c) to a rehab facility on 4/23/21, where PPEF ONS was unavailable. Patient was placed on a standard intact dairy based ONS. Patient was readmitted to the hospital on 5/14/21 with weight loss of 2.7kg. Patient was placed back on standard, intact calorically dense PPEF ONS during readmission, where he drank 1–2 per day until d/c back to rehab facility 5 days later.ConclusionsThis case report demonstrates that PPEF ONS was a viable alternative nutritional therapy to promote weight gain in this burn patient. A prospective study looking at objective measures, such as nutritional status and inflammatory markers, in burn patients on plant-based enteral formulas in the acute care setting is necessary.Funding SourcesN/A.

Flattening of circadian glucocorticoid oscillations drives acute hyperinsulinemia and adipocyte hypertrophy.

Disruption of circadian glucocorticoid oscillations in Cushing's disease and chronic stress results in obesity and adipocyte hypertrophy, which is believed to be a main source of the harmful effects of obesity. Here, we recapitulate stress due to jet lag or work-life imbalances by flattening glucocorticoid oscillations in mice. Within 3days, mice achieve a metabolic state with persistently high insulin, but surprisingly low glucose and fatty acids in the bloodstream, that precedes a more than 2-fold increase in brown and white adipose tissue mass within 3weeks. Transcriptomic and Cd36-knockout mouse analyses show that hyperinsulinemia-mediated de novo fatty acid synthesis and Cd36-mediated fatty acid uptake drive fat mass increases. Intriguingly, this mechanism by which glucocorticoid flattening causes acute hyperinsulinemia and adipocyte hypertrophy is unexpectedly beneficial in preventing high levels of circulating fatty acids and glucose for weeks, thus serving as a protective response to preserve metabolic health during chronic stress.

Informal Food Vendors and the Obesogenic Food Environment of an Informal Settlement in Nairobi, Kenya: A Descriptive and Spatial Analysis

ObjectivesThe objective of this study was to characterize the food environment of an informal settlement in Nairobi, Kenya according to the obesogenic properties and spatial distribution of informal food vendors. MethodsFrom July 15 to August 9, 2019, we identified 524 vendors in the informal settlement of Kibera. Guided by the NOVA classification system for food processing, we dichotomized foods sold into categories of high- vs. low-risk and protective vs. non-protective with respect to their propensity to promote weight gain. Then, we classified vendors into obesogenic risk groups based on a 1/3 cutpoint for the proportion of high-risk and protective foods sold: 1) low-risk, protective, 2) low-risk, non-protective, 3) high-risk, protective, 4) high-risk, non-protective. We calculated descriptive statistics of the types of foods sold according to vendor type and obesogenic risk group. To assess clustering by obesogenic risk, for each group, we calculated the mean distance to the nearest vendor of the same group, and used Ripley’s K function and 100 Monte Carlo simulations to identify significant clustering. ResultsThe 456 vendors in the analytic sample included approximately 30% stands, 29% kiosks, 17% market stalls, 13% hawkers, and 12% restaurants. Foods most commonly sold were sweets/confectionary (29% of vendors), raw vegetables (28%), fried starches (23%), and fruits (21%). Forty-four % of vendors were classified as low-risk, protective, 34% as high-risk, non-protective, 16% as low-risk, non-protective, and 6% as high-risk, protective. The mean distance (95% CI) to the nearest vendor of the same group was 26 m (21, 31) for vendors in the low-risk, protective group, 29 m (25, 33) in the high-risk, non-protective group, 114 m (88,139) in the high-risk, protective group, and 43 m (30, 56) in the low-risk, non-protective group. Clustering was significant for all obesogenic risk groups except high-risk, protective. ConclusionsOur findings demonstrate a duality of obesogenic and non-obesogenic foods in this environment. Clustering of vendors selling obesogenic foods highlights the need for strategies to ensure consistent access to health-promoting foods throughout informal settlements. Funding SourcesUNC-Chapel Hill Department of Nutrition; Robertson Scholars Leadership Program at Duke University; NHLBI predoctoral traineeship.

Sugar-Sweetened Beverage and 100% Fruit Juice Consumption on Body Weight in Children and Adults: A Systematic Review and Meta-Analysis

ObjectivesSugar-sweetened beverages (SSBs) have been increasingly linked to the obesity epidemic, however, the evidence on 100% fruit juice and body weight remains controversial. The objective of this research was to synthesize the available evidence on SSBs and 100% fruit juice on body weight in children and adults.MethodsMEDLINE, EMBASE, and Cochrane were searched through October 11th, 2020 for prospective cohort studies (≥ 6 months) and randomized controlled trials (RCTs) (≥ 2 weeks) assessing the effect of SSBs and 100% fruit juice on BMI and body weight in children and adults. Eligible trials assessed SSBs or 100% fruit juice added to the diet in adults, and reduced from the diet in children against a non-caloric control. Data were pooled using random effects models and presented as b coefficients with 95% CIs for cohort studies and mean differences (MD)s with 95% CIs for RCTs. Results are reported in compliance with the PRISMA guidelines, and the protocol was registered on PROSPERO (ID: CRD42020209915).ResultsSixty-two articles were identified for SSBs: 40 in children (33 cohorts, 7 RCTs) and 22 in adults (14 cohorts, 8 RCTs), and 22 articles were identified for 100% fruit juice: 13 in children (13 cohorts, 0 RCTs), and 9 studies in adults (3 cohorts, 6 RCTs). Among cohort studies, each serving/day increase in SSB was associated with an increase in BMI in children and body weight in adults (0.06 kg/m2; 95% CI: 0.03, 0.10 and 0.47 kg; 95% CI: 0.24, 0.69, respectively). For 100% fruit juice, each serving/day increase was associated with an increase in body weight in adults (0.19 kg; 95% CI: 0.04, 0.34) while no association was found for children (0.02 kg/m2; 95% CI: −0.01, 0.05). RCTs in children indicated a reduction in BMI gain when SSB consumption was reduced (MD = −0.21 kg/m2; 95% CI: −0.42, 0.00). RCTs in adults indicated an increase in body weight when SSBs were added to the diet (MD = 0.76 kg; 95% CI: 0.51, 1.0), however no effect on weight was found for the addition of 100% fruit juice (MD = 0.08 kg; 95% CI: −0.79, 0.96).ConclusionsSSB consumption promotes weight gain in both children and adults. Evidence from cohort studies indicate a positive association between 100% fruit juice and weight gain in adults and a marginal association among children. Findings from RCTs on 100% fruit juice in adults showed no effect, and there is a need for trials among children.Funding SourcesNone.

Dietary Succinate Impacts the Nutritional Metabolism, Protein Succinylation and Gut Microbiota of Zebrafish

Succinate is widely used in the food and feed industry as an acidulant, flavoring additive, and antimicrobial agent. This study investigated the effects of dietary succinate on growth, energy budget, nutritional metabolism, protein succinylation, and gut microbiota composition of zebrafish. Zebrafish were fed a control-check (0% succinate) or four succinate-supplemented diets (0.05, 0.10, 0.15, and 0.2%) for 4 weeks. The results showed that dietary succinate at the 0.15% additive amount (S0.15) can optimally promote weight gain and feed intake. Whole body protein, fat, and energy deposition increased in the S0.15 group. Fasting plasma glucose level decreased in fish fed the S0.15 diet, along with improved glucose tolerance. Lipid synthesis in the intestine, liver, and muscle increased with S0.15 feeding. Diet with 0.15% succinate inhibited intestinal gluconeogenesis but promoted hepatic gluconeogenesis. Glycogen synthesis increased in the liver and muscle of S0.15-fed fish. Glycolysis was increased in the muscle of S0.15-fed fish. In addition, 0.15% succinate-supplemented diet inhibited protein degradation in the intestine, liver, and muscle. Interestingly, different protein succinylation patterns in the intestine and liver were observed in fish fed the S0.15 diet. Intestinal proteins with increased succinylation levels were enriched in the tricarboxylic acid cycle while proteins with decreased succinylation levels were enriched in pathways related to fatty acid and amino acid degradation. Hepatic proteins with increased succinylation levels were enriched in oxidative phosphorylation while proteins with decreased succinylation levels were enriched in the processes of protein processing and transport in the endoplasmic reticulum. Finally, fish fed the S0.15 diet had a higher abundance of Proteobacteria but a lower abundance of Fusobacteria and Cetobacterium. In conclusion, dietary succinate could promote growth and feed intake, promote lipid anabolism, improve glucose homeostasis, and spare protein. The effects of succinate on nutritional metabolism are associated with alterations in the levels of metabolic intermediates, transcriptional regulation, and protein succinylation levels. However, hepatic fat accumulation and gut microbiota dysbiosis induced by dietary succinate suggest potential risks of succinate application as a feed additive for fish. This study would be beneficial in understanding the application of succinate as an aquatic feed additive.

Psychopharmacologic Management of Eating Disorders.

Identifying medications that may be used as therapeutic agents for eating disorders is a longstanding focus of research, with varying degrees of success. The present review consolidates the most recent findings on pharmacological treatment of three eating disorders, including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Recent research suggests that olanzapine demonstrates positive effects on weight gain among outpatients with AN. There are fewer recent advances in psychopharmacological treatment for BN and BED, likely due to the relative success of prior medication trials. Olanzapine is the first medication to safely promote weight gain among individuals with AN. Fluoxetine is FDA-approved for BN treatment, and lisdexamfetamine is FDA-approved for BED treatment. BN and BED also generally respond well to SSRIs prescribed off-label. Research on psychopharmacological treatments for other eating disorders, such as avoidant-restrictive food intake disorder and other specified feeding and eating disorders, are sorely needed.

The functional role of fecal microbiota transplantation on Salmonella Enteritidis infection in chicks

The intestinal microbiota plays important roles in animal health and growth. We investigated the efficacy and mechanisms of fecal microbiota transplantation (FMT) from adult SPF chickens against Salmonella Enteritidis (SE) infection in chicks. We transplanted 160 recipient SPF chicks (1-day-old) that were randomly divided into four groups, Ca (challenge), Cb (non-challenge), Fa (FMT and challenge) and Fb (FMT without challenge). The experiment lasted 40 days. We found that FMT reduced mortality as well as liver inflammatory lesions, promoted weight gain, improved immunity, ameliorated the digestion and absorption ability and inhibited SE colonization in the liver of challenged chicks. 16S rRNA gene high-throughput sequencing indicated that SE challenge caused a significant increase in the relative abundance of Parasutterella in the cecal microbiota of the recipient chicks (P < 0.05). FMT led to the maturation of the intestinal flora of recipients and the relative abundance of the Bacteroides, Rikenellaceae_ RC9_ gut_ group, Prevotellaceae_ UCG_ 001, Prevotellaceae_ Ga6A1_ group and Parabacteroides was significantly increased (P < 0.05). FMT from adult SPF chickens regulated the intestinal microbiota of chicks and increased resistance to SE infection.

Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review.

The approval of once daily liraglutide, 3.0 mg, and once weekly semaglutide, 2.4 mg, for chronic weight management provides a novel effective strategy against obesity. The reliable models that might predict weight reducing potential at the individual level have not been identified yet. However, the coexistence of diabetes has been consistently related with less effective response than in people without this comorbidity. We aimed to review the efficacy of GLP-1 RAs approved for weight management in individuals with and without diabetes and discuss some potential mechanisms for consistently observed differences in efficacy between these two populations. The mean weight loss difference between GLP-1 RAs and placebo as add-on to lifestyle intervention in patients with diabetes was 4% to 6.2% compared to 6.1 to 17.4% in people without diabetes. Semaglutide compared to liraglutide resulted in greater weight loss. Some hypothetical explanations for the weaker anti-obesity response for both GLP-1 RAs in people with diabetes include the background medications that promote weight gain, the fear of hypoglycaemia inherently related to the treatment of diabetes, a decrease in glycosuria and subsequently less weight loss in diabetics, an altered microbiota in patients with obesity and diabetes and a genetic background that predispose to weight gain in patients with diabetes. Moreover, people with diabetes may have had obesity for longer and may be less adherent to exercise, which seems to potentiate the effects of GLP-1 RA. Emerging multimodal approaches combining peptides targeting receptors at different levels might therefore be of additional benefit particularly in patients with diabetes.

The energy balance model of obesity: beyond calories in, calories out

A recent Perspective article described the "carbohydrate-insulin model (CIM)" of obesity, asserting that it "better reflects knowledge on the biology of weight control" as compared with what was described as the "dominant energy balance model (EBM)," which fails to consider "biological mechanisms that promote weight gain." Unfortunately, the Perspective conflated and confused the principle of energy balance, a law of physics that is agnostic as to obesity mechanisms, with the EBM as a theoretical model of obesity that is firmly based on biology. In doing so, the authors presented a false choice between the CIM and a caricature of the EBM that does not reflect modern obesity science. Here, we present a more accurate description of the EBM where the brain is the primary organ responsible for body weight regulation operating mainly below our conscious awareness via complex endocrine, metabolic, and nervous system signals to control food intake in response to the body's dynamic energy needs as well as environmental influences. We also describe the recent history of the CIM and show how the latest "most comprehensive formulation" abandons a formerly central feature that required fat accumulation in adipose tissue to be the primary driver of positive energy balance. As such, the new CIM can be considered a special case of the more comprehensive EBM but with a narrower focus on diets high in glycemic load as the primary factor responsible for common obesity. We review data from a wide variety of studies that address the validity of each model and demonstrate that the EBM is a more robust theory of obesity than the CIM.

Bifidobacterium infantis treatment promotes weight gain in Bangladeshi infants with severe acute malnutrition.

Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition. Bifidobacterium longum subspecies infantis is a prominent early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs). We found that the absolute abundance of Bifidobacterium infantis is lower in 3- to 24-month-old Bangladeshi infants with severe acute malnutrition (SAM) compared to their healthy age-matched counterparts. A single-blind, placebo-controlled trial (SYNERGIE) was conducted in 2- to 6-month-old Bangladeshi infants with SAM. A commercial U.S. donor-derived B. infantis strain (EVC001) was administered daily with or without the HMO lacto-N-neotetraose for 28 days. This intervention increased fecal B. infantis abundance in infants with SAM, although to levels still 10- to 100-fold lower than in untreated healthy controls. EVC001 treatment promoted weight gain that was associated with reduced intestinal inflammation markers in infants with SAM. We cultured fecal B. infantis strains from Bangladeshi infants and colonized gnotobiotic mice with these cultured strains. The gnotobiotic mice were fed a diet representative of that consumed by 6-month-old Bangladeshi infants, with or without HMO supplementation. One B. infantis strain, Bg_2D9, expressing two gene clusters involved in uptake and utilization of N-glycans and plant-derived polysaccharides, exhibited superior fitness over EVC001. The fitness advantage of Bg_2D9 was confirmed in a gnotobiotic mouse model of mother-to-infant gut microbiota transmission where dams received a pretreatment fecal community from a SAM infant in the SYNERGIE trial. Whether Bg_2D9 is superior to EVC001 for treating malnourished infants who consume a diet with limited breastmilk requires further clinical testing.

Male Infertility in the XXI Century: Are Obesogens to Blame?

The permanent exposure to environmental contaminants promoting weight gain (i.e., obesogens) has raised serious health concerns. Evidence suggests that obesogens are one of the leading causes of the marked decline in male fertility and are key players in shaping future health outcomes, not only for those who are directly exposed to them, but also for upcoming generations. It has been hypothesized that obesogens affect male fertility. By using an interdisciplinary strategy, combining in silico, in vitro, in vivo and epidemiological findings, this review aims to contribute to the biological understanding of the molecular transformations induced by obesogens that are the basis of male infertility. Such understanding is shaped by the use of Adverse Outcomes Pathways, a new approach that may shift the paradigm of reproductive toxicology, contributing to the improvement of the diagnosis and management of the adverse effects of obesogens in male fertility.

Relationship Between Serum Brain-Type Natriuretic Peptide and Biomarkers of Growth in Infants With Shunt-Dependent Single Cardiac Ventricle

For infants with shunt-dependent or ductal-dependent single ventricle heart disease, poor growth is common and associated with morbidity and impaired neurodevelopmental outcomes. Although attention has focused on nutrition to promote weight gain, little is known about the relation between heart failure and growth factors. A prospective observational pilot study was performed to assess the relation between heart failure, assessed by brain natriuretic peptide (BNP), and growth factors (insulin-like growth factor 1 [IGF-1] and insulin-like growth factor-binding protein 3) at 3 visits: (1) before discharge from neonatal intervention with the establishment of stable pulmonary blood flow, (2) immediately before superior cavopulmonary connection, and (3) before discharge after superior cavopulmonary connection operation. The relation between BNP and growth factors was analyzed using Spearman pairwise correlations at each visit and modeled over time with a linear mixed-effects model. Correlations were considered worthy of further exploration using a p <0.10, given the exploratory nature of the study. The study included 38 infants (66% male, 68% hypoplastic left heart syndrome). Median BNP was elevated at visit 1 and decreased over time (287pg/dl [interquartile range 147 to 794], 85pg/dl [52 to 183], and 90pg/dl [70 to 138]). Median IGF-1 Zscore was <0 at each visit but increased over time (-0.9 [interquartile range -1.1 to 0.1], -0.7 [-1.2 to 0.1], and -0.5 [-1.2 to 0]). Inverse correlations were found between BNP and IGF-1 at visit 1 (r=-0.40, p=0.097), BNP and IGF-1 and insulin-like growth factor-binding protein 3 at visit 2 (r=-0.33, p=0.080 and r=-0.33, p=0.085, respectively) and BNP and IGF-1 Zscore at visit 3 (r=-0.42, p=0.049). Significant relations were likewise found between the change in BNP and the change in IGF-1 between visits 1 and 3 (p=0.046) and between visits 2 and 3 (p=0.048). In conclusion, this pilot study demonstrates an inverse correlation between BNP and growth factors, suggesting that the heart failure state associated with this physiology may play a mechanistic role in impaired growth.

Nonylphenol Polyethoxylates Enhance Adipose Deposition in Developmentally Exposed Zebrafish.

Alkylphenol polyethoxylates (APEOs), such as nonylphenol ethoxylates (NPEOs), are high-production-volume surfactants used in laundry detergents, hard-surface cleaners, pesticide formulations, textile production, oils, paints, and other products. NPEOs comprise −80% of the total production of APEOs and are widely reported across diverse environmental matrices. Despite a growing push for replacement products, APEOs continue to be released into the environment through wastewater at significant levels. Research into related nonionic surfactants from varying sources has reported metabolic health impacts, and we have previously demonstrated that diverse APEOs and alcohol polyethoxylates promote adipogenesis in the murine 3T3-L1 pre-adipocyte model. These effects appeared to be independent of the base alkylphenol and related to the ethoxylate chain length, though limited research has evaluated NPEO exposures in animal models. The goals of this study were to assess the potential of NPEOs to promote adiposity (Nile red fluorescence quantification) and alter growth and/or development (toxicity, length, weight, and energy expenditure) of developmentally exposed zebrafish (Danio rerio). We also sought to expand our understanding of the ability to promote adiposity through evaluation in human mesenchymal stem cells. Herein, we demonstrated consistent adipogenic effects in two separate human bone-marrow-derived mesenchymal stem cell models, and that nonylphenol and its ethoxylates promoted weight gain and increased adipose deposition in developmentally exposed zebrafish. Notably, across both cell and zebrafish models we report increasing adipogenic/obesogenic activity with increasing ethoxylate chain lengths up to maximums around NPEO-6 and then decreasing activity with the longest ethoxylate chain lengths. This research suggests metabolic health concerns for these common obesogens, suggesting further need to assess molecular mechanisms and better characterize environmental concentrations for human health risk assessments.

Cold Exposure Drives Weight Gain and Adiposity following Chronic Suppression of Brown Adipose Tissue.

Therapeutic activation of thermogenic brown adipose tissue (BAT) may be feasible to prevent, or treat, cardiometabolic disease. However, rodents are commonly housed below thermoneutrality (~20 °C) which can modulate their metabolism and physiology including the hyperactivation of brown (BAT) and beige white adipose tissue. We housed animals at thermoneutrality from weaning to chronically supress BAT, mimic human physiology and explore the efficacy of chronic, mild cold exposure (20 °C) and β3-adrenoreceptor agonism (YM-178) under these conditions. Using metabolic phenotyping and exploratory proteomics we show that transfer from 28 °C to 20 °C drives weight gain and a 125% increase in subcutaneous fat mass, an effect not seen with YM-178 administration, thus suggesting a direct effect of a cool ambient temperature in promoting weight gain and further adiposity in obese rats. Following chronic suppression of BAT, uncoupling protein 1 mRNA was undetectable in the subcutaneous inguinal white adipose tissue (IWAT) in all groups. Using exploratory adipose tissue proteomics, we reveal novel gene ontology terms associated with cold-induced weight gain in BAT and IWAT whilst Reactome pathway analysis highlights the regulation of mitotic (i.e., G2/M transition) and metabolism of amino acids and derivatives pathways. Conversely, YM-178 had minimal metabolic-related effects but modified pathways involved in proteolysis (i.e., eukaryotic translation initiation) and RNA surveillance across both tissues. Taken together these findings are indicative of a novel mechanism whereby animals increase body weight and fat mass following chronic suppression of adaptive thermogenesis from weaning. In addition, treatment with a B3-adrenoreceptor agonist did not improve metabolic health in obese animals raised at thermoneutrality.

Metabolic dysfunctions promoted by AIN-93G standard diet compared with three obesity-inducing diets in C57BL/6J mice.

Researchers from different fields have studied the causes of obesity and associated comorbidities, proposing ways to prevent and treat this condition by using a common animal model of obesity to create a profound energy imbalance in young adult rodents. However, to confirm the harmful effects of consuming a high-fat and hypercaloric diet, it is common to include normolipidic and normocaloric control groups in the experimental protocols. This study compared the effect of three experimental diets described in the literature - namely, a high-fat diet, a high-fat and high-sucrose diet, and a high-fat and high-fructose diet - to induce obesity in C57BL/6J mice with the standard AIN-93G diet as a control. We hypothesize that the AIN diet formulation is not a good control in this type of experiment because this diet promotes weight gain and metabolic dysfunctions similar to the hypercaloric diet. The metabolic data of animals fed the AIN-93G diet were similar to those of the high-calorie groups (development of steatosis and hyperlipidemia). However, it is important to emphasize that the group fed a high-fat diet had a higher percentage of total fat (p=0.0002) and abdominal fat (p=0.013) compared to the other groups. Also, the high-fat group responded poorly to glucose and insulin tolerance tests, showing a picture of insulin resistance. As expected, the intake of the AIN-93G diet promotes metabolic alterations in the animals like the high-fat formulations. Therefore, although this diet continues to be used as the gold standard for growth and maintenance, it warrants a reassessment of its composition to minimize the metabolic changes observed in this study, thus updating its fitness as a normocaloric model of a standard rodent diet.