Greater Weight Gain Research Articles

Dietary substitution effect of Saccharina japonica with residues of citrus juice production in formulated diets on the growth, body composition and air exposure of juvenile abalone (Haliotis discus, Reeve 1846)

Dietary substitution effect of Saccharina japonica with residues of citrus juice production (RCJP) on the growth and body composition of abalone (Haliotis discus) subjected to air exposure was determined. A total of 1260 abalone were randomly distributed into 18 net cages (seventy per cage). Five formulated diets were prepared. The control (RCJP0) diet included 20% S. japonica. The percentages of 25, 50, 75 and 100 of S. japonica were substituted with the same amount of RCJP, referred to as the RCJP25, RCJP50, RCJP75 and RCJP100 diets, respectively. Finally, dry S. japonica was prepared to evaluate the formulated diets on growth performance of abalone. Each diet was randomly assigned to triplicate groups of abalone. Abalone were daily fed to satiety with little leftover for 16 weeks. After the 16-week feeding trial, abalone were subjected to air exposure stressor for 20 h, and then survival was monitored for the next 120 h. All formulated diets achieved significantly greater weight gain and specific growth rate (SGR) than those of abalone fed the S. japonica. Weight gain and SGR of abalone linearly improved with an increased substitution levels of S. japonica with RCJP in feeds. The greatest weight gain and SGR were obtained in abalone fed the RCJP100 diet. The shell growth and soft body weight of abalone also linearly increased with dietary substitution levels of S. japonica with RCJP. The chemical composition of the soft body of abalone was not affected by the experimental diets. Survival of abalone fed all formulated diets, except for the RCJP0 diet was significantly higher than that of abalone fed the S. japonica at the end of the 120-h post observation. In conclusion, S. japonica could be entirely (100%) replaced with RCJP in formulated abalone diet. The greatest growth performance was obtained in abalone fed the RCJP100 diet.

Restricted feeding and dietary energy levels affect liver structure in cultured Yellowtail Kingfish ( Seriola lalandi , Valenciennes) at summer water temperatures

Excess dietary lipids may be stored as lipid droplets in liver hepatocytes where they cannot be transported from the cells. Yellowtail kingfish (Seriola lalandi, Valenciennes) are cultured using formulated feeds, putting them at risk of fatty livers. This study investigated the effect of restricted feeding (apparent satiation [100%] vs. apparent sub-satiation [80%]) and three different dietary energy levels (Diet 1 [19.0 MJ kg−1 gross energy], Diet 2 [20.2 MJ kg−1 gross energy] and Diet 3 [18.4 MJ kg−1 gross energy]) on liver structure and function of sub-adult Yellowtail kingfish (1.87 ± 0.01, mean kg ±SE) over 84 days. Fish fed to 100% satiation had significantly (p < 0.05) greater weight gain than fish fed to 80% satiation. Both hepatosomatic index (HSI; %) and vacuolization levels of liver hepatocytes were unaffected by restricted feeding, but significantly (p = 0.016 and p = 0.039, respectively) increased with an increase in dietary energy. Fish fed high-energy diets showed extensive large hepatocyte vacuolization. Despite these adverse changes, results reported elsewhere showed that increased dietary energy level improved the overall growth performance and feed utilization of sub-adult Yellowtail kingfish compared with fish fed lower energy/lipid diets. Therefore, high-energy diets have the potential to be used in the production of Yellowtail kingfish.

Prenatal and Perinatal Factors and Risk of Cancer in Middle and Older Adulthood among Men.

Prenatal factors have been associated with risk of cancers later in life, although studies in men have largely been case-control and focused on birth size only. We used data from 5,845 men in the Health Professionals Follow-up Study (HPFS) to prospectively examine associations between several prenatal and perinatal factors and incident adult cancer risk. In 1994, mothers of participants reported information on characteristics and behaviors related to their pregnancy with their sons. We used multivariable Cox proportional hazards models to calculate HRs and 95% confidence intervals (CI) of associations between prenatal and perinatal risk factors and cancer risk. During 20 years of follow-up, 1,228 incident cases of overall cancer were documented. Men with a birth weight of ≥4 kg had a 21% increased risk of overall cancer (HR, 1.21; 95% CI, 1.02-1.43) compared with those with a birth weight of 2.5 to 3.9 kg. Greater weight gain during pregnancy (>13.6 kg vs. 6.8-8.6 kg) was also associated with a higher risk of overall cancer (HR, 1.22; 95% CI, 1.02-1.46), and was stronger for men whose mothers had a prepregnancy BMI<21 kg/m2 (HR, 1.30; 95% CI, 1.00-1.67) compared with body mass index (BMI) ≥21 kg/m2 (HR, 1.14; 95% CI, 0.85-1.51). There was no association between maternal age and overall cancer risk. Higher birth weight and maternal weight gain are associated with increased cancer risk in adult men. Our findings support the hypothesis that the in utero environment plays a role in the etiology of cancer in middle and older adulthood.

Long-term weight gain after initiating combination antiretroviral therapy in treatment-naïve Asian people living with human immunodeficiency virus

To investigate changes in weight following the initiation of antiretroviral therapy in treatment-naïve Asian people living with human immunodeficiency virus (PLWH). This retrospective observational study evaluated adult treatment-naïve Asian PLWH who started antiretroviral therapy based on an integrase strand transfer inhibitor, a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor at the AIDS Clinical Centre, Tokyo between January 2005 and February 2019. Patients were followed-up until October 2019. Multi-variate linear mixed-effects models were used to generate marginal predictions of weight over time. Predicted weight was reported at 3-month intervals until censoring or for 5 years after treatment initiation. Five years after treatment initiation, average weight gain in PLWH who started on dolutegravir-, darunavir- and elvitegravir-based treatment was 5.3 kg, 4.1 kg and 4.6 kg, respectively, while those who started on raltegravir-, lopinavir- and atazanavir-based treatment gained an average of 1.9 kg, 2.1 kg and 2.3 kg, respectively. Average weight gain in PLWH who started treatment with the backbone drugs, tenofovir alafenamide, abacavir and tenofovir disproxil fumarateb was 4.1 kg, 3.0 kg and 3.0 kg, respectively, and those treated with dolutegravir plus tenofovir alafenamide/emtricitabine gained an average of 6.7 kg. Antiretroviral-therapy-associated weight gain continued to increase for 5 years following treatment initiation. A combination of dolutegravir and tenofovir alafenamide/emtricitabine was associated with the greatest weight gain.

Impact of a standardised parenteral nutrition protocol: a quality improvement experience from a NICU of a developing country

ObjectiveNutrition societies recommend using standardised parenteral nutrition (SPN) solutions. We designed evidence-based SPN formulations for neonates admitted to our neonatal intensive care unit (NICU) and evaluated their outcomes.DesignThis was a...

A pilot study exploring the effect of repetitive transcranial magnetic stimulation (rTMS) treatment on cerebral blood flow and its relation to clinical outcomes in severe enduring anorexia nervosa

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a novel treatment option for people with severe enduring anorexia nervosa (SE-AN), but associated neurobiological changes are poorly understood. This study investigated the effect of rTMS treatment on regional cerebral blood flow (CBF) and whether any observed changes in CBF are associated with changes in clinical outcomes in people with SE-AN.MethodsAs part of a randomised sham-controlled feasibility trial of 20 sessions of high-frequency rTMS to the left dorsolateral prefrontal cortex, 26 of 34 trial participants completed arterial spin labelling (ASL) functional magnetic resonance imaging (fMRI) to quantify regional and global resting state CBF before (pre-randomisation baseline) and after real or sham treatment (1-month post-randomisation). A group of healthy females (n = 30) were recruited for baseline comparison. Clinical outcomes, including BMI, and depression and anxiety symptoms, were assessed at baseline, 1-, 4-, and 18-months post-randomisation.ResultsNo group differences in regional CBF were identified between the SE-AN and healthy comparison participants. A significant treatment-by-time interaction in a medial temporal lobe cluster with the maximal peak in the right amygdala was identified, reflecting a greater reduction in amygdala CBF following real rTMS compared to sham. Participants with the greatest rTMS-related reduction in amygdala CBF (i.e., between baseline and 1-month post-randomisation) showed the greatest sustained weight gain at 18-months post-randomisation. Higher baseline CBF in the insula predicted greater weight gain between baseline and 1-month post-randomisation and between baseline and 4-months post-randomisation.ConclusionsThis exploratory pilot study identified rTMS treatment related changes in CBF in adults with SE-AN and these were associated with changes in weight. Our preliminary findings also suggest that CBF (as measured by ASL fMRI) may be a marker of rTMS treatment response in this patient group. Future rTMS studies in AN should employ longitudinal neuroimaging to further explore the neurobiological changes related to rTMS treatment.Trial registrationISRCTN14329415, registered 23rd July 2015.

Avaliação de sistemas de produção e análise econômica de cabritos lactentes criados na região semiárida da Paraíba

The objective of this study was to evaluate the performance and economic indicators of baby goats region submitted to different feeding systems in the Semiarid. A total of 30 baby goats of breed Parda Alpina × without defined racial pattern (SPRD) with initial weight of 3.35 kg ± 0.65 kg and final weight of 12.3 kg ± 0.5 kg were used, distributed in a completely randomized design in three breastfeeding systems with ten replicates each: traditional system (with natural breastfeeding), intensive breastfeeding system without concentrated supplementation, and intensive breastfeeding with concentrated supplementation. Goats submitted to the intensive artificial feeding system without concentrated supplementation showed a similar weight gain (121 g/day) when compared to the goats submitted to the system of suckling with concentrated supplementation (126 g/day). The highest income was provided by the animals submitted to the intensive system of suckling with concentrate. The gross margin for the two centenarians was positive, that is, revenues are higher than the effective operating cost, allowing us to conclude that the activity is paying off and will survive, at least in the short term. The diet of kids using concentrate provided better dry matter intake, greater weight gain and consequently presented better economic indicators.

Hazelnut Modulates Neurobehaviour and Ameliorates Ageing-induced Oxidative Stress, and Caspase-3-Mediated Apoptosis in Mice.

Organismal aging has been associated with deleterious effects in different body tissues and organs, including the brain. There have been reports from ancient medicinal scripts of the beneficial effects of nuts like hazelnut in preventing aging induced-brain atrophy and memory loss. This study examined the potential beneficial effects of a diet supplemented with two different (Italian and Turkish) cultivars of hazelnut on the brain of aged mice. Aged (24 months old) mice were randomly assigned into 7 groups of ten mice each. Mice were grouped as standard diet (SD) control, three groups of Turkish and three groups of Italian hazelnut incorporated into SD at 2, 4 and 8% respectively. Animals were fed standard or hazelnut diet for 8 weeks. On day 56, behaviours in the elevated plus maze, radial-arm maze, open field, and Y-maze paradigms were monitored and scored, following which animals were euthanized. The brains were removed, weighed and homogenized for the assessment of specific biochemical tests. Results showed that hazelnut-supplemented diet was associated with significantly increased weight gain, with the Italian hazelnut being associated with greater weight gain. The hazelnut- supplemented diet also increased behavioural parameters such as horizontal locomotion and grooming, while it decreased rearing activity. Working-memory also improved significantly with both cultivars of hazelnut, while anxiety indices were reduced at lower concentrations of Italian, and higher concentrations of Turkish hazelnut. Both hazelnut varieties were associated with a reduction in acetylcholinesterase activity, superoxide dismutase activity, nitric oxide levels, caspase- 3 level, but increased dopamine level. Overall, hazelnut cultivars have beneficial effects on the brain in aged mice; suggesting a possible role in the prevention or management of age-related neurodegenerative changes.

Abstract 2584: Leukemia latency in the mCG-PML-RARα mouse model is impacted by sex and obesity

Abstract Human leukemias have been reported to show sexual dimorphism in both incidence and behavior. However, few studies of this observation have been conducted in animal models. We used the C57BL/6J mouse, genetically engineered to contain the PML-RARA fusion gene at the mouse cathepsin G (mCG) locus, as a model (B6.mCG-PML-RARα) of acute promyelocytic leukemia (APL) to interrogate the impact of sex and diet variation on disease latency as measured by leukemia-free survival. At 30 days of age, control (WT) and mutant (mCG+/PR) mice were separated by sex and provided with high fat (HF) [57% coconut oil fat] or low fat (LF) [10% coconut oil fat] diets. Mice were followed with serial blood collections and sacrificed when peripheral blood revealed signs of leukemia development including elevated granulocytes (WBC &amp;gt;20 K/μL), anemia (Hb &amp;lt;11 g/dL), and thrombocytopenia (PLT &amp;lt;600 K/μL). At necropsy, leukemic mice were noted to have marked splenomegaly (0.73±0.40 g) compared to controls (0.30±0.19 g). However, splenomegaly was not affected by diet in WT mice, as spleen size was consistent in both HF and LF diet-fed animals. mCG+/PR male mice fed HF diets showed greater weight gain and were significantly (P&amp;lt;0.001) heavier than mCG+/PR male mice fed LF diets (45.1±6.6 g versus 31.3±2.9 g at 150 days on diet). Female mCG+/PR mice fed HF diets showed greater weight gain than female mCG+/PR mice fed LF diets (31.8±5.5 g versus 23.2±1.9 g at 150 days on diet). In addition, mCG+/PR male mice fed HF diets were significantly heavier than female mCG+/PR mice fed HF diets (45.1±6.6 g versus 31.8±5.5 g at 150 days on diet). This sexual dimorphism in weight accumulation has been previously noted and attributed in part to ovarian function. The longest latency for the appearance of APL was shown in female mCG+/PR mice fed LF diets, where a median leukemia-free survival (MLFS) of &amp;gt;425 days was observed. In contrast, male mCG+/PR mice fed LF diets showed a reduced MLFS of 360 days of age, indicating a difference in latency of 65 days, thereby demonstrating sexual dimorphism in the appearance of APL. HF diet accelerated the appearance of APL in both female (MLFS = 277 days of age) and male mCG+/PR mice (MLFS = 277 days of age), which also displayed a difference in latency of 65 days. Thus, HF diet accelerated appearance of APL by 148 days in male and 148 days in female mCG+/PR mice. There were no signs of leukemia development in WT mice on either HF or LF diets. There was no splenomegaly observed in WT mice on either HF or LF diets. Thus, although HF diet and obesity accelerate the onset of APL in B6.mCG-PML-RARα mice, sexual dimorphism remains, with females showing extended latency compared to males under conditions of both HF and LF diets. Overall, our studies provide a robust mouse model to study the mechanisms by which sex impacts leukemia latency, as well as demonstrate that obesity accelerates leukemia development without affecting sexual dimorphism. Citation Format: John W. Kincaid, Annie E. Hill-Baskin, Nathan A. Berger. Leukemia latency in the mCG-PML-RARα mouse model is impacted by sex and obesity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2584.

Effects of Ovariectomy-Induced Estrogen Deficit on Rat Behaviour, Lipid Metabolism, Inflammation, Bone Mineral Density, and Turnover

The objective of the present study was to make a complex evaluation of behaviour, lipid metabolism, inflammation, and bone turnover in an ovariectomized rat model used to simulate postmenopausal clinical findings. Female Wistar rats were divided into 2 groups of 16 animals each: sham operated (SO) animals and ovariectomized (OVX) animals. Three months after the operation, a battery of behavioural tests was performed including an open field test (OFT), elevated pus-maze test (EPM), the social interaction test (SIT), the forced swim test (FST), and a hot plate test (HPT). At termination of experiment, weight gain and fat deposits (total and retroperitoneal) were measured. Serum concentrations of blood lipids were determined. Tumor necrosis factor alpha (TNF-alpha) and alkaline phosphatase (ALP) serum concentrations were used for evaluation of the inflammation and bone turnover, respectively. Femur bone mineral density (BMD) was evaluated using dual energy X-ray absorptiometry. OVX rats did not demonstrate any significant behavioural changes in OFT and EPM tests but showed a decreased interaction time in SIT and an increased immobility time in FST test which indicated anxiety and depression. The OVX rats had a significantly lower pain sensitivity threshold. They had greater weight gain, increased total and retroperitoneal fat deposits, as well as elevated total fat/body weight and retroperitoneal fat/body weight ratios. Blood cholesterol, ALP and TNF-alpha of the OVX group were also significantly higher. Femur BMD of OVX rats was slightly but not significantly reduced. Estrogen deficiency in OVX rats caused depression, anxiety, hyperalgesia, obesity, dyslipidemia, and inflammation before the reduction in bone mineral density was prominent.

Weight Change and Predictors of Weight Change Among Patients Initiated on Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide or Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Real-World Retrospective Study

Background: Recent evidence suggests that integrase strand transfer inhibitors are associated with greater weight gain than protease inhibitors in patients with human immunodeficiency virus (HIV-1). Objectives: To describe demographic and clinical characteristics of insured patients with HIV-1 in the United States initiating darunavir/​cobicistat/​emtricitabine/​tenofovir alafenamide (DRV/c/FTC/TAF) or bictegravir/FTC/TAF (BIC/FTC/TAF), assess the differences in weight and body mass index (BMI) change between cohorts up to one year after treatment initiation, and identify the predictors of weight gain associated with each treatment. Methods: The Symphony Health, IDV® database (July 17, 2017 – September 30, 2019) was used to identify treatment naïve or virologically suppressed stable switchers who initiated DRV/c/FTC/TAF or BIC/FTC/TAF (index date) on or after July 17, 2018, were ≥18 years of age on the index date, and had ≥12 months of continuous clinical activity pre-index (baseline period). To account for differences in baseline characteristics, inverse-probability of treatment weighting (IPTW) was used. Mean weight and BMI change from pre- to post-index measurements were compared between weighted cohorts at 3, 6, 9, and 12 months post-index using mean differences. Predictors of weight or BMI gain ≥5% were evaluated at last measurement, for each treatment cohort separately. Results: After IPTW, 452 and 497 patients were included in the DRV/c/FTC/TAF and BIC/FTC/TAF cohorts, respectively. Baseline characteristics were generally well-balanced (mean age=~50 years, female: ~30%), except for the type of antiretroviral therapy from which patients switched. Patients initiated on BIC/FTC/TAF experienced greater weight and BMI increases between the pre-index period and each measurement of the post-index period than patients initiated on DRV/c/FTC/TAF, although results were only statistically significant at 9 months post-index (weight: mean difference=2.50 kg, P=0.005; BMI: mean difference=0.66 kg/m2, P=0.027). A common predictor of weight or BMI gain ≥5% among patients in both cohorts was female gender (DRV/c/FTC/TAF: odds ratio [OR]=5.92, P=0.014; BIC/FTC/TAF: OR=2.00, P&lt;0.001). Conclusion: Patients in the BIC/FTC/TAF cohort experienced greater weight and BMI increases than patients in the DRV/c/FTC/TAF cohort, with differences reaching statistical significance at 9 months post-index. Weight gain is an important factor to consider when selecting antiretroviral regimens, since it is associated with long-term health consequences. Future studies with larger sample size and longer follow-up time are warranted.

Weight Change and Predictors of Weight Change Among Patients Initiated on Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide or Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Real-World Retrospective Study

Background: Recent evidence suggests that integrase strand transfer inhibitors are associated with greater weight gain than protease inhibitors in patients with human immunodeficiency virus (HIV-1). Objectives: To describe demographic and clinical characteristics of insured patients with HIV-1 in the United States initiating darunavir/​cobicistat/​emtricitabine/​tenofovir alafenamide (DRV/c/FTC/TAF) or bictegravir/FTC/TAF (BIC/FTC/TAF), assess the differences in weight and body mass index (BMI) change between cohorts up to one year after treatment initiation, and identify the predictors of weight gain associated with each treatment. Methods: The Symphony Health, IDV® database (July 17, 2017 – September 30, 2019) was used to identify treatment naïve or virologically suppressed stable switchers who initiated DRV/c/FTC/TAF or BIC/FTC/TAF (index date) on or after July 17, 2018, were ≥18 years of age on the index date, and had ≥12 months of continuous clinical activity pre-index (baseline period). To account for differences in baseline characteristics, inverse-probability of treatment weighting (IPTW) was used. Mean weight and BMI change from pre- to post-index measurements were compared between weighted cohorts at 3, 6, 9, and 12 months post-index using mean differences. Predictors of weight or BMI gain ≥5% were evaluated at last measurement, for each treatment cohort separately. Results: After IPTW, 452 and 497 patients were included in the DRV/c/FTC/TAF and BIC/FTC/TAF cohorts, respectively. Baseline characteristics were generally well-balanced (mean age=~50 years, female: ~30%), except for the type of antiretroviral therapy from which patients switched. Patients initiated on BIC/FTC/TAF experienced greater weight and BMI increases between the pre-index period and each measurement of the post-index period than patients initiated on DRV/c/FTC/TAF, although results were only statistically significant at 9 months post-index (weight: mean difference=2.50 kg, P=0.005; BMI: mean difference=0.66 kg/m2, P=0.027). A common predictor of weight or BMI gain ≥5% among patients in both cohorts was female gender (DRV/c/FTC/TAF: odds ratio [OR]=5.92, P=0.014; BIC/FTC/TAF: OR=2.00, P&lt;0.001). Conclusion: Patients in the BIC/FTC/TAF cohort experienced greater weight and BMI increases than patients in the DRV/c/FTC/TAF cohort, with differences reaching statistical significance at 9 months post-index. Weight gain is an important factor to consider when selecting antiretroviral regimens, since it is associated with long-term health consequences. Future studies with larger sample size and longer follow-up time are warranted.

Weight Change and Predictors of Weight Change Among Patients Initiated on Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide or Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Real-World Retrospective Study.

Background: Recent evidence suggests that integrase strand transfer inhibitors are associated with greater weight gain than protease inhibitors in patients with human immunodeficiency virus (HIV-1).Objectives: To describe demographic and clinical characteristics of insured patients with HIV-1 in the United States initiating darunavir/​cobicistat/​emtricitabine/​tenofovir alafenamide (DRV/c/FTC/TAF) or bictegravir/FTC/TAF (BIC/FTC/TAF), assess the differences in weight and body mass index (BMI) change between cohorts up to one year after treatment initiation, and identify the predictors of weight gain associated with each treatment.Methods: The Symphony Health, IDV® database (July 17, 2017 – September 30, 2019) was used to identify treatment naïve or virologically suppressed stable switchers who initiated DRV/c/FTC/TAF or BIC/FTC/TAF (index date) on or after July 17, 2018, were ≥18 years of age on the index date, and had ≥12 months of continuous clinical activity pre-index (baseline period). To account for differences in baseline characteristics, inverse-probability of treatment weighting (IPTW) was used. Mean weight and BMI change from pre- to post-index measurements were compared between weighted cohorts at 3, 6, 9, and 12 months post-index using mean differences. Predictors of weight or BMI gain ≥5% were evaluated at last measurement, for each treatment cohort separately.Results: After IPTW, 452 and 497 patients were included in the DRV/c/FTC/TAF and BIC/FTC/TAF cohorts, respectively. Baseline characteristics were generally well-balanced (mean age=~50 years, female: ~30%), except for the type of antiretroviral therapy from which patients switched. Patients initiated on BIC/FTC/TAF experienced greater weight and BMI increases between the pre-index period and each measurement of the post-index period than patients initiated on DRV/c/FTC/TAF, although results were only statistically significant at 9 months post-index (weight: mean difference=2.50 kg, P=0.005; BMI: mean difference=0.66 kg/m2, P=0.027). A common predictor of weight or BMI gain ≥5% among patients in both cohorts was female gender (DRV/c/FTC/TAF: odds ratio [OR]=5.92, P=0.014; BIC/FTC/TAF: OR=2.00, P<0.001).Conclusion: Patients in the BIC/FTC/TAF cohort experienced greater weight and BMI increases than patients in the DRV/c/FTC/TAF cohort, with differences reaching statistical significance at 9 months post-index. Weight gain is an important factor to consider when selecting antiretroviral regimens, since it is associated with long-term health consequences. Future studies with larger sample size and longer follow-up time are warranted.

Comparative effectiveness of liquid human milk fortifiers: A systematic review and meta-analysis.

To determine the effectiveness of liquid human milk fortifiers (HMFs) derived from exclusive HM or hydrolyzed protein on growth, necrotizing enterocolitis (NEC), or late-onset sepsis in North American very low-birth-weight (VLBW) infants compared with powder HMFs (control). Prospective trials published between 2009 and 2020 were systematically reviewed, and meta-analysis was conducted by using a random-effects model. Five studies were identified for up to 591 participants across 39 centers. Study treatments included whey or casein hydrolysate HMF and exclusive HM HMF. Infants fed whey or casein hydrolysate HMF had growth differences compared with the control. No differences were found across treatments in regard to NEC or sepsis. Very low-quality evidence suggests greater linear growth in VLBW infants fed whey hydrolysate liquid HMF, as well as greater weight gain in those fed casein hydrolysate HMF, compared with the control. Additional prospective, multicenter randomized controlled trials are needed to confirm these estimates because of sparsity of evidence. There is insufficient evidence to support HMF decisions regarding NEC or late-onset sepsis prophylaxis.

The set point: weight destiny established before adulthood?

Although the set point is one of the best understood weight defense mechanisms, how and when a set point is established and what causes its disruption are not well understood. The purpose of this review is to address these gaps in the literature by exploring studies on the establishment of the set point theory and the underlying metabolic processes that support its existence. Research suggests that weight loss achieved through restricted energy intake and increased energy expenditure is difficult to maintain and is often followed by greater weight gain over time. It is hypothesized that such weight gain is driven by an individual's set point, a weight range in which the body seeks to remain by adjusting metabolism (e.g. by moderating energy expenditure based on energy intake in times of diet or energy fluctuation). Similar to adults, weight loss in adolescence results in decreased resting metabolic rate (RMR), and that the RMR remains suppressed even with weight restoration. Recommending weight loss in youth results in metabolic adaptations to restore weight and weight inclusive approaches may be more appropriate to protect their health and wellbeing.

271-OR: ADA Presidents’ Select Abstract: MyD88 Signaling in Trophoblasts Is Necessary for Maternal High-Fat Diet-Associated Developmental Programming of Obesity

Maternal obesity (OB) contributes to programming of offspring obesity. A causal role for placental inflammatory mechanisms in developmental programming remains to be established. We examined the role of the toll-like receptor (TLR) pathway in mediating maternal obesity associated programming by trophoblast deletion of the TLR adapter protein MyD88. We generated MyD88fl/fl:Cyp19 Cre+ (conditional-KO, MyD88-CKO) and MyD88fl/fl:Cyp19 Cre- (flox-control, f/f) mice. Beginning at 5 wk of age, female MyD88-CKO mice were fed ad libitum control (17% fat calories, TD95092) or high-fat diets (HFD, 45% fat calories, TD08811) for 12 wk and then bred with lean MyD88fl/fl:Cyp19 Cre-(flox-control) males (fed control diet). This breeding strategy generated 50% of placenta/offspring with the Myd88-CKO genotype and genetically matched f/f littermate controls. At weaning, offspring (n = 10-12 from distinct litters) were randomized to control or HFD for 16 wk. All offspring have normal TLR signaling, since Cyp19 activity is only present in the placenta. Deletion of placental MyD88 had no effect on offspring growth on control diet. Male f/f offspring from HFD-dams fed HFD showed greater weight gain relative to f/f offspring from control-fed dams fed HFD, indicating an effect of maternal HFD. However, this effect of maternal HFD was not present in MyD88-CKO offspring from HFD-dams fed HFD, revealing a pivotal role for placental TLR signaling in the maternal HFD programming of obesity. Transcriptomic analyses of sex-identified placenta at dpc 17.5 showed that HFD altered more genes in male placenta (864 vs. 580, ±1.5 fold, p&amp;lt;0.05) in a MyD88-dependent manner. Gene ontology analyses showed that alterations in genes related to inflammation, extracellular matrix, and mitochondrial function were absent in placenta lacking MyD88. These findings provide the first unequivocal evidence that placental changes due to maternal HFD are causally related to offspring obesity risk. Disclosure M. L. Ruebel: None. K. M. Thakali: None. S. V. Chintapalli: None. K. Shankar: None. Funding U.S. Department of Agriculture (ARS-CRIS 6026-51000-012-00-D)

Abstract P116: Higher Body Mass Index Trajectories Are Associated With Lower Levels Of Physical Activity Measured By A Smartwatch

Introduction: The prevalence of obesity is rising. Most previous studies that examined the relationship between body mass index (BMI) and physical activity measured BMI at a single time-point, ignoring the time-varying nature of BMI. The relationship between BMI trajectories and habitual physical activity in community settings remains unclear. Objective: To assess the relationship between BMI trajectories and habitual physical activity measured by daily steps from a smartwatch, among participants enrolled in the electronic Framingham Heart Study (eFHS). We hypothesized that participants whose BMI trajectories increased over a 14-year period prior to the step assessment take fewer daily steps, compared to participants who maintained stable BMI trajectories during the same time period. Methods: We used a semiparametric group-based modelling method to identify BMI trajectory patterns. Participants who attended exams 1, 2, and 3 were included in building the trajectories. Daily steps were recorded from the smartwatch provided at exam 3 with “active days” defined as days with ≥ 5watch wear-hours. We excluded participants with &lt;30 active days. The median follow-up period for step count was 357 days (IQR: 467 days). We used generalized linear models that accounted for correlation between daily steps in the same individuals to examine the longitudinal relationship between BMI trajectory groups and daily step counts, adjusting for relevant covariates. Results: We identified three trajectory groups for the 837 eFHS participants. Group 1 included 292 participants (mean age 54 years, 57% women) whose BMI was stable (slope: 0.005, p=0.75); Group 2 included 468 participants (mean age 53 years, 56% women) whose BMI increased slightly (slope: 0.123, p&lt;9.2e-17); and Group 3 included 77 participants (mean age 50 years, 70% women) who had the largest increase of BMI (slope: 0.318, p=2.8e-22).Adjusting for age, sex, wear time and race/ethnicity, participants in group 3 (Δ1437 steps P&lt; 0.0001) and Group 2 (Δ422 steps, P=0.04) took significantly fewer steps, compared to participants in Group 1 (Model 1). The effect sizes were slightly attenuated but remained significant after additionally adjusting for hypertension, type 2 diabetes, current smoking, and cardiovascular disease: Group 3 took 1258 fewer steps, P=0.0001; Group 2 took 406 fewer steps, P=0.04 (Model 2). We further adjusted for sleep apnea, education, and marital status in Model 3 and observed that on average Group 3 took 1120 fewer steps (P= 0.0007) and Group 2 took 382 fewer steps (P= 0.06), compared to Group 1. Conclusion: Participants whose BMI trajectory increased over time took significantly fewer steps compared to participants with more stable BMI trajectories. Our findings suggest that levels of physical activity may correlate with greater weight gain during adulthood.

Multiplying effects of COVID-19 lockdown on metabolic risk and fatty liver.

BackgroundSocial containment measures imposed in Europe during the lockdown to face COVID‐19 pandemic can generate long‐term potential threats for metabolic health.MethodsA cohort of 494 non‐COVID‐19 subjects living in 21 EU countries were interviewed by an anonymous questionnaire exploring anthropometric and lifestyle changes during 1‐month lockdown. A subgroup of 41 overweight/obese Italian subjects with previously diagnosed nonalcoholic fatty liver (NAFLD) joined the study following a 12‐month follow‐up period promoting weight loss by healthy lifestyle.ResultsDuring the lockdown, body weight increased in 55% of subjects (average 2.4 ± 0.9 kg). Weight change increased with age, but not baseline body mass index. Subjects living in Italy had greater weight gain than those living in other European Countries. Weight gain during the lockdown was highest in subjects reporting no physical activity, and low adherence to Mediterranean diet. In the NAFLD group, weight gain occurred in 70% of cases. Subjects reporting weight loss during lockdown had decreased fatty liver score at 3 months before the lockdown, as compared with 1 year before.ConclusionsStrict measures of social containment—even short‐term—pave the way to the increased risk of metabolic abnormalities in the medium‐long term. In this context, adherence to Mediterranean diet and regular physical activity play a protective role both in terms of weight gain and fatty liver development/progression, with implication for primary and secondary prevention. When adopting measures imposing social containment, intensive educational campaigns must increase public awareness about beneficial effects of healthy lifestyles.

Visual dysfunction in a mouse model of chemotherapy-related neurotoxicity.

e24059 Background: Chemotherapy-related neurotoxicity (CRNT) poses challenges to long-term outcomes of cancer survivors. Visual function remains relatively unexplored in CRNT. Preliminary clinical work from our group suggests contrast sensitivity may be impaired in patients receiving chemotherapy. Here, we sought to isolate effects of chemotherapy on visual dysfunction in a mouse model. Methods: 10-week old C57BL/6J mice received either 4, 7, or 10 weekly intraperitoneal injections of chemotherapy (CTX group; n=15) or physiologic saline (SAL group; n=12). CTX mice received cyclophosphamide (50 mg/kg) and doxorubicin (2 mg/kg). Contrast sensitivity was assessed using an optomotor response (OMR) chamber. Psychometric functions were fitted to OMR contrast response functions to derive measures of contrast sensitivity (K), stimulus responsivity (Rmax), and stimulus selectivity (n). Electroretinography (ERG) waveforms, which measure light-evoked retinal neural activity, were recorded under scotopic (rod-driven) conditions and decomposed to isolate photoreceptor (a-wave), bipolar cell (b-wave), and interneuron amacrine cell (oscillatory potentials [OP]) activity. OMR and ERG were measured prior to and following treatment. Dependent- and independent-sample t-tests assessed within- and between-group changes, respectively, in outcome measures. Results: Outcome measures are reported in Table 1. SAL relative to CTX mice showed greater weight gain (p=0.004). OMR revealed increases in Rmax (pCTX=0.002; pSAL=0.11) and K (pCTX=0.80; pSAL=0.06) parameters in SAL but not CTX mice. ERG results revealed significant declines in OP peak frequency in CTX relative to SAL mice (p=0.006). Other OMR and ERG measures showed no within- or between-group differences (p&gt;0.10). Decreases in weight were associated with decreases in Rmax (R2=0.25, p=.008) and OP peak frequency (R2=0.20, p=.02). Conclusions: Our animal model showed chemotherapy-related visual dysfunction. Mice receiving chemotherapy showed relative declines in contrast sensitivity, stimulus responsivity, and oscillatory neural activity, suggestive of disrupted neuronal circuits within the visual pathway. Future studies will focus on understanding neuronal mechanisms of visual pathway dysfunction and translating findings to clinical studies. [Table: see text]

Weight Change Following Antiretroviral Therapy Switch in People With Viral Suppression: Pooled Data from Randomized Clinical Trials.

We sought to identify factors associated with weight gain in randomized clinical trials of antiretroviral therapy (ART) switch. We explored the effects of demographic factors, clinical characteristics, and ART on weight gain in a pooled analysis of 12 prospective clinical trials, wherein virologically suppressed people living with human immunodeficiency virus (PWH) were randomized to switch or remain on a stable baseline regimen (SBR). Both PWH randomized to switch ART (n = 4166) and those remaining on SBR (n = 3150) gained weight. Median weight gain was greater in those who switched (1.6 kg, interquartile range [IQR], -.05 to 4.0 vs 0.4 kg, [IQR], -1.8 to 2.4 at 48 weeks, P < .0001), with most weight gain occurring in the first 24 weeks after switch. Among baseline demographic and clinical characteristics, only younger age and lower baseline body mass index were associated with any or ≥10% weight gain. By week 48, 4.6% gained ≥10% weight (6.4% of switch and 2.2% of SBR), the greatest risk was with switch from efavirenz (EFV) to rilpivirine (RPV) or elvitegravir/cobicistat and switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). Switch from abacavir to TAF was associated with less weight gain than switch from TDF to TAF and was not associated with increased risk for ≥10% weight gain. Moderate weight gain after ART switch was common and usually plateaued by 48 weeks. Baseline ART was a predictor of post-switch weight gain; participants who switched off of EFV and TDF had the greatest weight gain. The biological mechanisms that underlie the differential effects of switching ART agents on weight and associated clinical implications require further study.