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Cachexia is a life-threatening complication of cancer that occurs in up to 80% of patients with advanced cancer. Cachexia reflects the systemic consequences of cancer and prominently features unintended weight loss and skeletal muscle wasting. Cachexia impairs cancer treatment tolerance, lowers quality of life, and contributes to cancer-related mortality. Effective treatments for cancer cachexia are lacking despite decades of research. High-throughput omics technologies are increasingly implemented in many fields including cancer cachexia to stimulate discovery of disease biology and inform therapy choice. In this paper, we present selected applications of omics technologies as tools to study skeletal muscle alterations in cancer cachexia. We discuss how comprehensive, omics-derived molecular profiles were used to discern muscle loss in cancer cachexia compared with other muscle-wasting conditions, to distinguish cancer cachexia from treatment-related muscle alterations, and to reveal severity-specific mechanisms during the progression of cancer cachexia from early toward severe disease.

The biological mechanisms through which physical activity reduces metastatic disease recurrence and mortality in cancer patients are not known. This review offers the hypothesis that physical activity reduces the risk of recurrence and mortality in cancer patients through two synergistic processes: 1) indirect (systemic) effects related to the host tumor microenvironment; and 2) direct (physical) effects on cancer cells.

To examine if eating behaviors in mothers with low income relate to attitudes toward infant feeding and whether associations differed between breastfeeding and formula-feeding mothers.Cross-sectional study.Forty postpartum women (aged ≥ 18 years, body mass index ≥ 25 andamp;lt; 40 kg/mlt;supgt;2lt;/supgt;) in the Louisiana Women, Infants, and Children program participated in a telehealth postpartum intervention for health and weight loss.Maternal eating behaviors and infant feeding styles, assessed 6-8 weeks after birth (baseline) using validated questionnaires.Significance was detected using independent t tests, chi-square tests for independence, or linear models (Pamp;lt; 0.05).Most mothers formula-fed (n = 27, 68%). In formula-feeding mothers, maternal disinhibition and perceived hunger were positively associated with restrictive infant feeding (β = 0.41, Pamp;lt;0.001 and β = 0.41, P = 0.001, respectively). These relationships were significantly higher (Δ = -0.85, P = 0.006 and Δ = -0.59, P = 0.003, respectively) than among breastfeeding mothers. Comparatively, pressuring/overfeeding was lower in formula-feeding mothers than among breastfeeding mothers with dietary restraint (Δ slopes: 1.06, P = 0.02).In this cohort of mothers with low income, maternal eating behavior was associated with infant feeding styles only when feeding modality was considered. Mothers may benefit from education on how their eating behaviors can influence their infants and children.

151 Background: Cachexia, seen in more than a third of patients with non-small cell lung cancer (NSCLC), directly leads to functional and survival detriments. As screening and interventions for cachexia and NSCLC improve, deficits of healthcare access and quality among patients disadvantaged by race and socioeconomic factors must be addressed. Methods: Through retrospective and prospective data collection, we established a cohort of 957 patients diagnosed with stage IV NSCLC between 2014-2020 in Dallas, Texas. Presence of cachexia at diagnosis was determined using consensus criteria for substantial (5% for BMI≥20 and 2% for BMI < 20) unintentional weight loss in the 6 months leading to diagnosis. Analyses including multivariate logistic regression and log-rank testing evaluated for significant associations of variables with cachexia incidence and survival. Results: Black race and Hispanic ethnicity independently associated with more than a 70% increased risk of cachexia at NSCLC diagnosis (Table; P < 0.05). Inclusion of private insurance status as a covariate diminished this finding for Hispanic patients only. Black patients presented at younger ages than White patients (Kruskal-Wallis P =0.0012; T-test P = 0.0002), with an average difference of 3 years. Cachexia at diagnosis was a major predictor of survival, highlighting the importance of addressing differential cachexia risk across race/ethnicity. Conclusions: The elevated cachexia risk observed for Black patients independent of insurance status reveals broader causative factors of disparity. A lack of private insurance may be a primary contributor in Hispanic cachexia prevalence. Targeting these differences could mitigate survival detriments linked to cachexia in minority groups. Supported contributors in broader NSCLC outcome inequities include poor representation in trials substantiating USPSTF guidelines as well as preventable barriers to primary and preventative care. Our interpretation of NSCLC outcome disparity in the context of cachexia demonstrates further consequences of these deficits. Moreover, our findings suggest novel targets for health policy by highlighting the prevalence of undiagnosed unintentional weight loss in minority populations with late-stage NSCLC.[Table: see text]

Mitochondria are essential to the onset and progression of cancer through energy production, reactive oxygen species regulation, and macromolecule synthesis. Genetic and functional adaptations of mitochondria to the tumor environment drive proliferative and metastatic potential. The advent of DNA and RNA sequencing removed critical barriers to the evaluation of genetic mediators of tumorigenesis. However, to date, methodological approaches to evaluate tumor mitochondrial function remain elusive and require technical proficiency limiting the feasibility, ultimately diminishing diagnostic and prognostic value in both experimental and clinical settings. Here, we outline a simple and rapid method to quantify rates of oxidative phosphorylation (OXPHOS) and electron transfer (ET) capacity in freshly excised solid tumor homogenates using high-resolution respirometry. The protocol can be reproducibly applied across species and tumor types as well as adapted to evaluate a diversity of mitochondrial ET pathways. Using this protocol, we demonstrate that mice bearing a luminal B mammary cancer exhibit defective nicotinamide adenine dinucleotide-linked respiration and reliance on succinate to generate adenosine triphosphate via OXPHOS.

Obesity is a complex pandemic, and its effective management involves addressing many different factors. This complexity has given rise to novel analytic methods, integrating intensive computational, engineering, and statistical techniques. Mathematical models are currently applied to inform clinical practice. At the 2017 The Korean Nutrition Society 50th Anniversary International Conference, the development of such models and their application to improve data accuracy and patient care during the pregnancy and postpartum periods were discussed.

e24098 Background: While cancer cachexia is associated with increased morbidity/mortality, little is known about longitudinal weight changes and opportunities for intervention pre- and post-diagnosis in this patient population. We therefore aimed to characterize body weight trajectories pre- and post- non-small cell lung cancer (NSCLC) diagnosis in patients without and with cachexia. Methods: Data were retrospectively extracted for each patient pre- and post-diagnosis of NSCLC from inpatient and outpatient visits within the UT Southwestern Medical Center Healthcare System. 3830 participants were screened with a NSCLC diagnosis between May 2005 to December 2019. Of these, 661 patients had a body weight recorded at cancer diagnosis and at least one body weight pre-diagnosis. The primary outcome was weight change over time. Other measures included defining associations between weight change and tumor pathology, stage of disease, and other clinical characteristics. Results: NSCLC patients without cachexia at cancer diagnosis were weight stable up to 12-months pre-diagnosis (+1.0±0.3% body weight; p = 0.01). Weight loss post-diagnosis was driven by stage of disease (stage 1/2: 0.4±0.5% body weight vs. stage 3/4: 4.8±0.9% body weight p = 0.0008) and treatment with chemotherapy (p < 0.0001). NSCLC patients with cachexia at cancer diagnosis lost weight pre-diagnosis (8.8±0.5% body weight; p < 0.0001), with 25% of this weight loss occurring between 6- and 12-months pre-diagnosis. Assessing weight change over 12 months opposed to 6 months resulted in a 32% increase in NSCLC patients with cachexia at cancer diagnosis (p = 0.006). By 12-months post-diagnosis, 62% of surviving late-stage and 45% of early-stage NSCLC patients had met the criteria for cachexia. Patients on average remained free of weight loss for 150±6.4 days or had pre-cachexia for 146±7.2 days prior to transitioning to a more advanced stage of the syndrome. Conclusions: Significant weight loss in NSCLC patients initiated as far back as 12 months prior to a cancer diagnosis as opposed to a shorter 6-month interval currently used to define patients with cachexia. Therefore, detection of earlier weight loss should be prioritized in high-risk NSCLC screening candidates. Finally, advanced NSCLC patients develop cachexia post-diagnosis irrespective of previous weight history, highlighting the impact of treatment iatrogenicity and/or refractory disease on cachexia development.

Background/objective Interest in healthy properties of food and nutrients as co-adjuvant in type-2 diabetes therapy has increased in recent years. Zinc supplementation trials have shown improvements in glycemic control in these patients, although it seems dependent on zinc status of the individuals. The objective of this study was to evaluate the relationship between zinc nutritional status and glucose homeostasis in patients with type-2 diabetes. Subjects/methods Eighty patients with well controlled type-2 diabetes were recruited and clinical, anthropometric and dietary evaluations were performed. One week after, insulin sensitivity and beta cell function were assessed by a modified Frequently Sampled Intravenous Glucose Tolerance Test. Zinc status was assessed by plasma zinc and the size of rapidly Exchangeable Zinc Pool (EZP); zinc intake was also determined. Glucagon concentration was evaluated in a subsample of 36 patients. Results Patients presented a normal zinc status although zinc intake was lower than recommended. Overall, no associations were observed between zinc status and glycemic control markers. Nevertheless, positive correlations were observed between EZP and fasting insulin concentration (ρ = 0.393, p = 0.021) and HOMA-IR (ρ = 0.386, p = 0.024) in women, and between plasma zinc concentration and HbA1c (ρ = 0.342, p = 0.020) in men. Conclusions No significant associations were found between zinc status and glycemic control parameters in patients with well-controlled type 2 diabetes and normal zinc status, although low-degree gender-dependent associations were observed. Further research is required to assess the role of zinc status in zinc deficient patients.

Background Less than one-third of women gain an appropriate amount of weight during pregnancy, which can influence the long-term health of both the mother and the child. Economically disadvantaged women are the most vulnerable to maternal obesity, excessive weight gain during pregnancy, and poor birth outcomes. Effective and scalable health care strategies to promote healthy weight gain during pregnancy specifically tailored for these women are lacking. Objective This paper presents the design and protocol of a biphasic, community-based eHealth trial, SmartMoms in WIC, to increase the adherence to healthy gestational weight gain (GWG) recommendations in low-income mothers receiving women, infant, and children (WIC) benefits. Methods Phase 1 of the trial included using feedback from WIC mothers and staff and participants from 2 community peer advisory groups to adapt an existing eHealth gestational weight management intervention to meet the needs of women receiving WIC benefits. The health curriculum, the format of delivery, and incentive strategies were adapted to be culturally relevant and at an appropriate level of health literacy. Phase 2 included a pragmatic randomized controlled trial across the 9 health care regions in Louisiana with the goal of enrolling 432 women. The SmartMoms in WIC intervention is an intensive 24-week behavioral intervention, which includes nutrition education and exercise strategies, and provides the technology to assist with weight management, delivered through a professionally produced website application. Results Phase 1 of this trial was completed in July 2019, and recruitment for phase 2 began immediately thereafter. All data are anticipated to be collected by Spring 2023. Conclusions The SmartMoms in WIC curriculum was methodically developed using feedback from community-based peer advisory groups to create a culturally relevant, mobile behavioral intervention for mothers receiving WIC benefits. The randomized clinical trial is underway to test the effectiveness of a sustainable eHealth program on the incidence rates of appropriate GWG. SmartMoms in WIC may be able to offer an innovative, cost-effective, and scalable solution for GWG management in women served by WIC. Trial Registration ClinicalTrials.gov NCT04028843; https://clinicaltrials.gov/ct2/show/NCT04028843 International Registered Report Identifier (IRRID) DERR1-10.2196/18211

BACKGROUND Less than one-third of women gain an appropriate amount of weight during pregnancy, which can influence the long-term health of both the mother and the child. Economically disadvantaged women are the most vulnerable to maternal obesity, excessive weight gain during pregnancy, and poor birth outcomes. Effective and scalable health care strategies to promote healthy weight gain during pregnancy specifically tailored for these women are lacking. OBJECTIVE This paper presents the design and protocol of a biphasic, community-based eHealth trial, SmartMoms in WIC, to increase the adherence to healthy gestational weight gain (GWG) recommendations in low-income mothers receiving women, infant, and children (WIC) benefits. METHODS Phase 1 of the trial included using feedback from WIC mothers and staff and participants from 2 community peer advisory groups to adapt an existing eHealth gestational weight management intervention to meet the needs of women receiving WIC benefits. The health curriculum, the format of delivery, and incentive strategies were adapted to be culturally relevant and at an appropriate level of health literacy. Phase 2 included a pragmatic randomized controlled trial across the 9 health care regions in Louisiana with the goal of enrolling 432 women. The SmartMoms in WIC intervention is an intensive 24-week behavioral intervention, which includes nutrition education and exercise strategies, and provides the technology to assist with weight management, delivered through a professionally produced website application. RESULTS Phase 1 of this trial was completed in July 2019, and recruitment for phase 2 began immediately thereafter. All data are anticipated to be collected by Spring 2023. CONCLUSIONS The SmartMoms in WIC curriculum was methodically developed using feedback from community-based peer advisory groups to create a culturally relevant, mobile behavioral intervention for mothers receiving WIC benefits. The randomized clinical trial is underway to test the effectiveness of a sustainable eHealth program on the incidence rates of appropriate GWG. SmartMoms in WIC may be able to offer an innovative, cost-effective, and scalable solution for GWG management in women served by WIC. CLINICALTRIAL ClinicalTrials.gov NCT04028843; https://clinicaltrials.gov/ct2/show/NCT04028843 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/18211

OBJECTIVE This study aimed to identify factors that may predispose women to excess gestational weight gain (GWG). METHODS Seventy-two healthy women with obesity (30 class I, 24 class II, 18 class III) expecting a singleton pregnancy were studied at 13 to 16 weeks gestation. Energy expenditure (EE) was measured during sleep (SleepEE, average EE from 0200-0500 hours) in a whole-room calorimeter, and total daily EE (TDEE) over 7 days using doubly labeled water. Glucose, insulin, thyroid hormones, and catecholamines were measured. RESULTS Body composition explained 70% variability in SleepEE, and SleepEE accounted for 67% to 73% of TDEE. Though there was no evidence of consistent low metabolism, there was considerable variability. Low SleepEE was associated with insulin resistance and low triiodothyronine concentrations (both P = 0.01). Physical activity level was 1.47 ± 0.02. For women with SleepEE within 100 kcal/d of their predicted EE, TDEE was significantly less than the estimate (2,530 ± 91 vs. 2,939 kcal/d; P

Background: Targeting mitochondrial function has regained traction as a viable anti-cancer strategy. Here, we characterized the phenotypic and transcriptomic landscape of human triple negative breast cancer (TNBC) cells following exposure to the mitochondrial uncoupler BAM15. Methods: Cell viability and IC50 were determined by MTS assay after treatment (24-hours) with doxorubicin, cyclophosphamide, or BAM15 (0-100 µM). Mitochondrial membrane potential (ΔΨm) was measured by TMRM staining in live (Annexin V negative) cells using flow cytometry after acute (15-minutes) and chronic (16-hours) exposure to BAM15. Untargeted RNA sequencing was conducted after chronic (16-hours) exposure to BAM15 (1, 10, and 20 µM). Differentially expressed genes were determined by using DESeq2 package in R with the following cutoffs: false discovery rate 1.5. Pathway enrichment analysis was then used to identify canonical signaling networks and upstream regulators and specific gene targets were validated by real-time qPCR. Results: BAM15 reduced cell viability with an IC50 similar to doxorubicin and superior to cyclophosphamide. Acute exposure to BAM15 reduced ΔΨm by ~60% which saturated at 1 µM. After 16-hour exposure to BAM15, ΔΨm recovered at 1 µM, but was reduced by ~40% at 10 and 20 µM conditions. Through untargeted sequencing, we identified 2108 transcripts that were differentially regulated by BAM15 (20 µM vs. vehicle), 968 of which were upregulated and 1140 downregulated. To contextualize these findings, we performed pathway enrichment analysis on genes differentially expressed by BAM15. Canonical signaling pathways related cell survival, proliferation, energy production, and DNA damage were differentially regulated by BAM15. A number of known transcriptional factors required for cell division, replication, and survival, including CCNE2, E2F1, CDC6, CDC20, MCM3, MCM6, AURKA, UBEC2C, and S100A4, were inhibited by BAM15. Notably, genes and pathways essential to ATP production, including both glycolysis and oxidative phosphorylation, were dramatically reduced by BAM15, including LDHA and MT-CO1. Conclusions: Taken together, these findings reveal transcriptomic signatures and canonical signaling pathways that mediate the pro-apoptotic and anti-proliferative effects of sustained mitochondrial uncoupling. Citation Format: Elizabeth R. Zunica, Christopher L. Axelrod, Eunhan Cho, Guillaume Spielmann, Shengping Yang, L Anne Gilmore, John P. Kirwan. Untargeted sequencing of human breast cancer reveals induction of pro-apoptotic and anti-proliferative transcriptional signatures in response to mitochondrial uncoupling [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 2145.

Objective Gestational weight gain (GWG) is associated with infant birth weight and childhood obesity; however, the patterns of GWG on infant birth weight are poorly understood. Methods This analysis in 16,218 mother-child dyads from Tianjin, China, determined the risk of infant size at birth according to GWG occurring throughout the first and second trimester (early GWG) or during the third trimester (late GWG), according to maternal prepregnancy BMI and the 2009 Institute of Medicine recommendations. Results Excessive GWG in early and late pregnancy had an increased risk for large-for-gestational-age (LGA) infants (odds ratio [OR]: 2.4; 95% confidence interval [CI]: 1.5-4.0, P

Background: Prepregnancy maternal obesity and excessive weight gain during pregnancy lead to significant morbidities in mothers and their children. Mothers who never return to their prepregnancy weight begin subsequent pregnancies at a greater weight and have a larger propensity for excess gestational weight gain and postpartum weight retention. Methods: In this pilot study, 40 postpartum women credentialed to receive postpartum women, infants, and children (WIC) service were randomized to usual care (“WIC Moms”) or a personalized health intervention delivered via a SmartPhone (“E-Moms”). Assessments, including body weight, vital signs, circumferences, and body composition, were completed at week 0 (6–8 weeks postpartum), week 8, and week 16. Results: Results are presented as change from week 0 at 16. As per the completers analysis, body weight change was not different between the groups (WIC Moms vs. E-Moms; 1.8 ± 0.9 vs. −0.1 ± 0.9 kg; p = 0.10), neither was the change in percent body fat (1.7 ...

Context Weight loss is prescribed to offset the deleterious consequences of polycystic ovary syndrome (PCOS), but a successful intervention requires an accurate assessment of energy requirements. Objective Describe energy requirements in women with PCOS and evaluate common prediction equations compared with doubly labeled water (DLW). Design Cross-sectional study. Setting Academic research center. Participants Twenty-eight weight-stable women with PCOS completed a 14-day DLW study along with measures of body composition and resting metabolic rate and assessment of physical activity by accelerometry. Main Outcome Total daily energy expenditure (TDEE) determined by DLW. Results TDEE was 2661 ± 373 kcal/d. TDEE estimated from four commonly used equations was within 4% to 6% of the TDEE measured by DLW. Hyperinsulinemia (fasting insulin and homeostatic model assessment of insulin resistance) was associated with TDEE estimates from all prediction equations (both r = 0.45; P = 0.02) but was not a significant covariate in a model that predicts TDEE. Similarly, hyperandrogenemia (total testosterone, free androgen index, and dehydroepiandrosterone sulfate) was not associated with TDEE. In weight-stable women with PCOS, the following equation derived from DLW can be used to determine energy requirements: TDEE (kcal/d) = 438 - [1.6 * Fat Mass (kg)] + [35.1 * Fat-Free Mass (kg)] + [16.2 * Age (y)]; R2 = 0.41; P = 0.005. Conclusions Established equations using weight, height, and age performed well for predicting energy requirements in weight-stable women with PCOS, but more precise estimates require an accurate assessment of physical activity. Our equation derived from DLW data, which incorporates habitual physical activity, can also be used in women with PCOS; however, additional studies are needed for model validation.

OBJECTIVE To conduct a secondary analysis designed to test whether gestational weight gain is the result of increased energy intake or adaptive changes in energy expenditures. METHODS In this secondary analysis, energy intake and energy expenditure of 45 pregnant women (body mass index [BMI] 18.5-24.9 [n=33] and BMI 25 or greater [n=12]) were measured preconceptionally and at 22 and 36 weeks of gestation. Energy intake was calculated as the sum of total energy expenditure measured by doubly-labeled water and energy deposition determined by the four-compartment body composition model. Measurements of weight, body composition, and basal metabolic rate were completed preconceptionally and 9, 22, and 36 weeks of gestation. Basal metabolic rate was measured by indirect calorimetry in a room calorimeter and activity energy expenditure by doubly-labeled water. RESULTS Energy intake from 22 to 36 weeks of gestation was significantly higher in high gainers (n=19) (3,437±99 kcal per day) compared with low+ideal gainers (n=26) (2,687±110, P

OBJECTIVE: On December 8-9, 2014, the Pennington Biomedical Research Center convened a scientific symposium to review the state-of-the-science and future directions for the study of developmental programming of obesity and chronic disease. The objectives of the symposium were to discuss: (i) past and current scientific advances in animal models, population-based cohort studies, and human clinical trials, (ii) the state-of-the-science of epigenetic-based research, and (iii) considerations for future studies.RESULTS: This symposium provided a comprehensive assessment of the state of the scientific field and identified research gaps and opportunities for future research in order to understand the mechanisms contributing to the developmental programming of health and disease.CONCLUSIONS: Identifying the mechanisms which cause or contribute to developmental programming of future generations will be invaluable to the scientific and medical community. The ability to intervene during critical periods of prenatal and early postnatal life to promote lifelong health is the ultimate goal. Considerations for future research including the use of animal models, the study design in human cohorts with considerations about the timing of the intrauterine exposure, and the resulting tissue-specific epigenetic signature were extensively discussed and are presented in this meeting summary. (Less)

Rationale Intimate partners and other informal caregivers provide unpaid tangible, emotional, and decision-making support for patients with cancer, but relatively little research has investigated the cancer experiences of sexual minority women (SMW) with cancer and their partners/caregivers. Objective This review addressed 4 central questions: 1) What social support do SMW with cancer receive from partners/caregivers? 2) What effect does cancer have on intimate partnerships or caregiving relationships of SMW with cancer? 3) What effects does cancer have on partners/caregivers of SMW with cancer? 4) What interventions exist to support partners/caregivers of SMW or to strengthen the patient-caregiver relationship? Method This systematic review, conducted in 2018 and updated in 2020, was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two independent coders screened abstracts and articles. Results In total, 550 unique records were screened; 42 articles were assessed for eligibility, and 18 were included in a qualitative synthesis. Most studies were U.S.-based, involved breast cancer, included intimate partners, had primarily white/Caucasian samples, and were cross-sectional. Sexual minority female participants reported that partners/caregivers often provide important social support, including emotional support, decision-making support, and tangible support. Effects of cancer on relationships with partners/caregivers were mixed, with some studies finding relationships remained stable and others finding cancer either increased closeness or disrupted relationships. Participants reported partners/caregivers often experience distress and may experience discrimination, discomfort disclosing sexual orientation, and a lack of sexual minority-friendly services. No studies involved an intervention targeting partners/caregivers or the dyadic relationship. Conclusions More work is needed to understand SMW with cancers other than breast cancer, and future work should include more racially, ethnically, and economically diverse samples. Longitudinal research will allow an examination of patterns of mutual influence and change in relationships. These steps will enable the development of interventions to support SMW with cancer and people close to them.

Purpose: Obesity is an independent risk factor for the development, morbidity, and mortality of breast cancer. Calorie restriction (CR) is the first line therapy for obesity management, with growing evidence and application in the treatment of breast cancer. In non-tumor bearing patients, ~20% of weight loss is attributed to reductions in skeletal muscle mass. However, little is known of how CR in a tumorigenic environment may influence muscle function and content. Methods: Obese C57BL/6J female mice were used to develop an allograft breast cancer model by orthotopically injecting the mammary fat pad with basal-like breast cancer (E0771 cells). Mice were randomized (1:1) by tumor size and body weight to high fat diet (HFD; 60% kcal from fat) or calorie restriction diet (CRD; ~40% restriction of HFD via an incremental reduction in food intake) for 2.5 weeks. Daily food intake, body weight and temperature, as well as twice weekly tumor measurements were obtained during treatment. Organ weights and size were obtained at the time of necropsy. Whole blood was collected for immunophenotyping and assessed via flow cytometry. Mitochondrial function was determined in tumor homogenates and permeabilized gastrocnemius fibers by high resolution respirometry (O2k). Results: CRD reduced body weight (HFD: 27.8±0.8 vs CRD: 22.9±0.5 g, P=0.0003) and tumor growth (HFD: 3.6±0.2 g vs. CRD: 2.7±0.3 g, P=0.03). There was no difference in the proportions of total NK cells, helper and cytotoxic T-cells between HFD and CRD (P>0.05). Respirometry studies of tumor mitochondria revealed diminished complex I uncoupled rate following CRD (HFD: 3.2±0.4 vs. CRD: 1.6±0.3 pmol/sec/mg, P= 0.02). Additionally, skeletal muscle mitochondria of CRD animals contained a defect in complex I oxidation (HFD: 49.2±6.5 vs. CRD: 28.6±4.0 pmol/sec/mg, P=0.03). Furthermore, soleus muscle mass was reduced (HFD: 7.7±0.8 mg vs. CRD: 4.5±1.1 mg, P=0.04). Conclusions: This study demonstrates that CRD induces complex I (CI) defects in tumor and skeletal muscle mitochondria. Suppression of CI was associated with a favorable reduction in tumor growth and unfavorable loss of skeletal muscle mass. Future studies formally evaluating skeletal muscle function and cachexia as well as muscle preserving therapies in combination with CR are warranted. Funding: Research was supported by NIGMS (GM104940 - JPK) and the Pennington Biomedical Research Foundation (LAG) Citation Format: Elizabeth R. Zunica, Christopher L. Axelrod, Gangarao Davuluri, Wagner S. Dantas, Guillaume Spielmann, Eunhan Cho, Brian A. Irving, John P. Kirwan, L. Anne Gilmore. Calorie restriction induces skeletal muscle wasting and a complex I defect while reducing mammary tumor growth in a mouse model of diet induced obesity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4796.

Calorie restriction (CR) triggers benefits for healthspan including decreased risk of cardiometabolic disease (CVD). In an ancillary study to CALERIE 2, a 24-mo 25% CR study, we assessed the cardiometabolic effects of CR in 53 healthy, nonobese (BMI: 22–28 kg/m2) men ( n = 17) and women ( n = 36). The aim of this study was to investigate whether CR can reduce risk factors for CVD and insulin resistance in nonobese humans and, moreover, to assess whether improvements are exclusive to a period of weight loss or continue during weight maintenance. According to the energy balance method, the 25% CR intervention ( n = 34) produced 16.5 ± 1.5% (mean ± SE) and 14.8 ± 1.5% CR after 12 and 24 mo (M12, M24), resulting in significant weight loss (M12 −9 ± 0.5 kg, M24 −9 ± 0.5 kg, P < 0.001). Weight was maintained in the group that continued their habitual diet ad libitum (AL, n = 19). In comparison to AL, 24 mo of CR decreased visceral (−0.5 ± 0.01 kg, P < 0.0001) and subcutaneous abdominal adipose tissue (−1.9 ± 0.2kg, P < 0.001) as well as intramyocellular lipid content (−0.11 ± 0.05%, P = 0.031). Furthermore, CR decreased blood pressure (SBP −8 ± 3 mmHg, P = 0.005; DBP −6 ± 2 mmHg, P < 0.001), total cholesterol (−13.6 ± 5.3 mg/dl, P = 0.001), and LDL-cholesterol (−12.9 ± 4.4 mg/dl, P = 0.005), and the 10-yr risk of CVD-disease was reduced by 30%. Homeostasis model assessment of insulin resistance (HOMA-IR) decreased during weight loss in the CR group (−0.46 ± 0.15, P = 0.003), but this decrease was not maintained during weight maintenance (−0.11 ± 0.15, P = 0.458). In conclusion, sustained CR in healthy, nonobese individuals is beneficial in improving risk factors for cardiovascular and metabolic disease such as visceral adipose tissue mass, ectopic lipid accumulation, blood pressure, and lipid profile, whereas improvements in insulin sensitivity were only transient.

Background African-American (AA) women have poorer pregnancy outcomes, and studies in nonpregnant women suggest a different etiology of weight gain in AA compared with white women. We hypothesized that physiologic factors such as low energy expenditure and physical activity would be present in AA compared with white women in pregnancy. Objective We aimed to identify physiologic risk factors for disordered energy balance in AA and white women early in pregnancy. Design This was a cross-sectional study in 66 pregnant women with obesity, between 14 and 16 wk of gestation. Energy intake was calculated using the intake-balance method. Energy expenditure was measured in free-living conditions [total daily energy expenditure (TDEE)] over 7 d with the use of doubly labelled water and during sleep [sleeping EE (SleepEE)] in a room calorimeter. Body composition was measured by air displacement plethysmography and physical activity by accelerometers. Markers of metabolic health were obtained from fasting blood and urine. Results AA (n = 34) and white (n = 32) women were comparable in age (mean ± SEM: 27.7 ± 0.6 y), enrollment body mass index [mean ± SEM (in kg/m2): 36.9 ± 0.7], and body fat (mean ± SEM: 45.0% ± 0.6%). AA women had more fat-free mass (P = 0.01) and tended to be more insulin-resistant (homeostasis model assessment of insulin resistance, P = 0.06). Energy intake was significantly lower in AA than in white women (2499 ± 76 compared with 2769 ± 58 kcal/d, P = 0.001), although absolute TDEE was comparable (AA: 2590 ± 77 kcal/d; white: 2711 ± 56 kcal/d; P = 0.21). After adjusting for body composition, TDEE was significantly lower in AA women (-231 ± 74 kcal/d, P = 0.003), as was SleepEE (-81 ± 37 kcal/d, P = 0.03). Physical activity, substrate oxidation, and metabolic biomarkers (triiodothyronine and thyroxine concentrations, catecholamine excretion) were not significantly different between groups. Conclusions Body mass-adjusted energy expenditure is significantly lower in AA than in white pregnant women. Energy intake recommendations for pregnancy do not consider this difference and may therefore overestimate energy requirements in AA women. This may lead to unintentional overeating and contribute to the disparity of excess gestational weight gain and postpartum weight retention that is more prevalent in AA women. This trial was registered at clinicaltrials.gov as NCT01954342.

Metabolic and behavioral changes that occur during pregnancy have well-known effects on maternal and fetal health during the immediate pregnancy and now are thought to be a catalyst for future health throughout later life. Recommendations for appropriate gestational weight gain (GWG) and lifestyle modifications during pregnancy have changed throughout history as more is known about this crucial time. Herein we discuss the current GWG recommendations and the impact of pregnancy and excess GWG gain on the current and future health of women and children including risk of obesity, gestational diabetes, type II diabetes, cardiovascular disease, and metabolic syndrome.

Objective There is an urgent need to adopt standardized nomenclature as it relates to gestational weight gain (GWG), a more uniform approach to calculate it, and hence quantifying adherence to the 2009 Institute of Medicine (IOM) guidelines. Methods This perspective highlights the varying methods used to estimate GWG and discuss the advantages and limitations of each. Results While these calculations could be argued to have a minimal impact on data at the population level, on the patient level, incorrectly estimating weight at conception can result in misclassification of preconception body mass index (BMI) and assignment of the IOM guidelines which inherently affect the prospective management of weight gain (and potential outcomes) during the current pregnancy. Conclusions This study recommends that preconception BMI and total GWG be determined objectively and total GWG be adjusted for length of gestation before assessing adherence to the IOM GWG guidelines.

Background: Estimates of energy intake (EI) in humans have limited validity. Objective: The objective was to test the accuracy and precision of the intake-balance method to estimate EI during weight gain induced by overfeeding. Design: In 2 studies of controlled overfeeding (1 inpatient study and 1 outpatient study), baseline energy requirements were determined by a doubly labeled water study and caloric titration to weight maintenance. Overfeeding was prescribed as 140% of baseline energy requirements for 56 d. Changes in weight, fat mass (FM), and fat-free mass (FFM) were used to estimate change in energy stores (ΔES). Overfeeding EI was estimated as the sum of baseline energy requirements, thermic effect of food, and ΔES. The estimated overfeeding EI was then compared with the actual EI consumed in the metabolic chamber during the last week of overfeeding. Results: In inpatient individuals, calculated EI during overfeeding determined from ΔES in FM and FFM was (mean ± SD) 3461 ± 848 kcal/d, which was not significantly (−29 ± 273 kcal/d or 0.8%; limits of agreement: −564, 505 kcal/d; P = 0.78) different from the actual EI provided (3490 ± 729 kcal/d). Estimated EI determined from ΔES in weight closely estimated actual intake (−7 ± 193 kcal/d or 0.2%; limits of agreement: −386, 370 kcal/d; P = 0.9). In free-living individuals, estimated EI during overfeeding determined from ΔES in FM and FFM was 4123 ± 500 kcal/d and underestimated actual EI (4286 ± 488 kcal/d; −162 ± 301 kcal or 3.8%; limits of agreement: −751, 427 kcal/d; P = 0.003). Estimated EI determined from ΔES in weight also underestimated actual intake (−159 ± 270 kcal/d or 3.7%; limits of agreement: −688, 370 kcal/d; P = 0.001). Conclusion: The intake-balance method can be used to estimate EI during a period of weight gain as a result of 40% overfeeding in individuals who are inpatients or free-living with only a slight underestimate of actual EI by 0.2–3.8%. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT00565149","term_id":"NCT00565149"}}NCT00565149 and {"type":"clinical-trial","attrs":{"text":"NCT01672632","term_id":"NCT01672632"}}NCT01672632.

As technology continues to develop rapidly, the incidence of obesity also continues to climb at an alarming rate. The increase in available technology is thought to be a contributor in the obesogenic environment, yet at the same time technology can also be used to intervene and improve health and health behaviors. This article reviews the components of effective weight management programs and the novel role that technology, such as SMS, websites, and smartphone apps, is playing to improve the success of such programs. Use of these modern technologies can now allow for individualized treatment recommendations to be delivered to individuals remotely, increased self-monitoring/tracking of health-related data, broader and more rapid dissemination of health information/recommendations, and increased patient–dietician/physician contact. The use of technology in weight management programs results in improved long-term weight management, and in most cases improved cost-effectiveness. Rather than blaming increased food intake and sedentary lifestyle on technology, rapidly developing and innovative technologies should be used to our advantage and deployed to combat the obesity epidemic.

Based on previous research with bovine peadipocytes, we hypothesized that infusion of arginine into the abomasum of Angus steers stimulates stearoyl-CoA desaturase (SCD) gene expression in bovine subcutaneous (s.c.) adipose tissue, and that this would be attenuated by conjugated linoleic acid (CLA). Growing Angus steers were infused abomasally with L-arginine 50 g/day; n = 13; provided as L-arginine HCl) or L-alanine (isonitrogenous control, 100 g/day; n = 11) for 14 days. For the subsequent 14 days, half of the steers in each amino acid group were infused with CLA (100 g/day). Body weight gain and average daily gain were unaffected (P0.15) by infusion of arginine or CLA into the abomasum. The plasma concentrations of cis-9, trans-11 and trans-10, cis-12 CLA were increased CLA infusion (P = 0.001) and infusion of arginine increased plasma arginine (P = 0.01). Compared with day 0, fatty acid synthase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase enzyme activities in s.c. adipose tissue increased by day 14 in steers infused with either alanine or arginine (all P0.01). NADP-MDH activity was higher (P = 0.01) in steers infused with arginine than in steers infused with arginine plus CLA by day 28, but lipid synthesis in vitro from glucose and acetate was unaffected by infusion of either arginine or CLA (P0.40). By day 28, C/EBPβ and SCD gene expression was higher, and CPT1β gene expression was lower, in s.c. adipose tissue of steers infused with arginine than in steers infused with alanine (±CLA) (P = 0.05). CLA decreased adipose tissue oleic acid (18:1n-9) in alanine- or arginine-infused steers (P = 0.05), although CLA had no effect on SCD gene expression. The data indicate that supplemental arginine promotes adipogenic gene expression and may promote lipid accumulation in bovine adipose tissue. L-Arginine may beneficially improve beef quality for human consumption.

Calorie restriction, without malnutrition, has been shown to increase longevity and delay the onset of chronic disease in various species. In this chapter, we review the different modalities which scientists and individuals have followed to achieve a sustained caloric deficit. These include traditional dietary restriction regimens of varying degrees, physical activity, alternate day fasting, and alternate day modified fasting. To evaluate the impact of these interventions on chronic disease risk and longevity, we critically evaluate the existing evidence concerning the physiological as well as the behavioral alterations induced by these interventions.

Background Accurate methods of assessing food intake in infants are needed to assess the relationship between infant feeding practices and risk of childhood obesity. Current methods are either subjective or have limited ability for use beyond clinical research settings. Objective To assess the accuracy of the RFPM to evaluate simulated milk intake including energy, macronutrient, and micronutrient intake compared to direct weighing within a controlled study. Methods Individuals were recruited to prepare three 2 fl oz, 4 fl oz, 6 fl oz, and 8 fl oz servings of infant formula and to capture photographs at different stages of preparation (dry powdered formula, prepared formula, and liquid waste) using the SmartIntake® application. Gram weights of the bottles were obtained by the RFPM and direct weighing. Using the United States Department of Agriculture National Nutrient Database for Standard Reference, energy, macronutrient, and micronutrient values were generated from gram weights. Results Intake of formula prepared from powder measured by the RFPM was equivalent to weighed intake within 7.5% equivalence bounds among all servings and each serving size. The mean difference between methods varied among servings sizes with the RFPM underestimating intake by 1.6 ± 0.4 kcals in 2 fl oz servings, 4.8 ± 0.6 kcals in 4 fl oz servings, and 6.2 ± 1.0 kcals in 6 fl oz servings, and overestimating intake by 0.1 ± 1.2 kcals in 8 fl oz servings. Bland-Altman analysis showed that the RFPM overestimated intake at lower levels food intake and underestimated intake at higher levels. Considering photographs of only the prepared formula bottle and the bottle with formula waste to simulate ready-to-feed formula and human breast milk, intake estimated by the RFPM was equivalent to the directly weighed intake within 7.5% for all servings. Conclusions The RFPM has higher accuracy than subjective methods and similar accuracy as compared to the objective methods in estimating simulated intake of milk and formula with lower burden to caregivers. The RFPM is a viable method for measuring intake in exclusively milk fed infants by caregivers in a controlled environment with potential for widespread use in research and clinical practice.

On December 8-9, 2014, the Pennington Biomedical Research Center convened a scientific symposium to review the state-of-the-science and future directions for the study of developmental programming of obesity and chronic disease. The objectives of the symposium were to discuss: (i) past and current scientific advances in animal models, population-based cohort studies, and human clinical trials, (ii) the state-of-the-science of epigenetic-based research, and (iii) considerations for future studies.This symposium provided a comprehensive assessment of the state of the scientific field and identified research gaps and opportunities for future research in order to understand the mechanisms contributing to the developmental programming of health and disease.Identifying the mechanisms which cause or contribute to developmental programming of future generations will be invaluable to the scientific and medical community. The ability to intervene during critical periods of prenatal and early postnatal life to promote lifelong health is the ultimate goal. Considerations for future research including the use of animal models, the study design in human cohorts with considerations about the timing of the intrauterine exposure, and the resulting tissue-specific epigenetic signature were extensively discussed and are presented in this meeting summary.

Background Synonymous with increased use of mobile phones has been the development of mobile health (mHealth) technology for improving health, including weight management. Behavior change theory (eg, the theory of planned behavior) can be effectively encapsulated into mobile phone-based health improvement programs, which is fostered by the ability of mobile phones and related devices to collect and transmit objective data in near real time and for health care or research professionals and clients to communicate easily. Objective To describe SmartLoss, a semiautomated mHealth platform for weight loss. Methods We developed and validated a dynamic energy balance model that determines the amount of weight an individual will lose over time if they are adherent to an energy intake prescription. This model was incorporated into computer code that enables adherence to a prescribed caloric prescription determined from the change in body weight of the individual. Data from the individual are then used to guide personalized recommendations regarding weight loss and behavior change via a semiautomated mHealth platform called SmartLoss, which consists of 2 elements: (1) a clinician dashboard and (2) a mobile phone app. SmartLoss includes and interfaces with a network-connected bathroom scale and a Bluetooth-connected accelerometer, which enables automated collection of client information (eg, body weight change and physical activity patterns), as well as the systematic delivery of preplanned health materials and automated feedback that is based on client data and is designed to foster prolonged adherence with body weight, diet, and exercise goals. The clinician dashboard allows for efficient remote monitoring of all clients simultaneously, which may further increase adherence, personalization of treatment, treatment fidelity, and efficacy. Results Evidence of the efficacy of the SmartLoss approach has been reported previously. The present report provides a thorough description of the SmartLoss Virtual Weight Management Suite, a professionally programmed platform that facilitates treatment fidelity and the ability to customize interventions and disseminate them widely. Conclusions SmartLoss functions as a virtual weight management clinic that relies upon empirical weight loss research and behavioral theory to promote behavior change and weight loss.

Background Infant formula is a major source of nutrition for infants, with more than half of all infants in the United States consuming infant formula exclusively or in combination with breast milk. The energy in infant powdered formula is derived from the powder and not the water, making it necessary to develop methods that can accurately estimate the amount of powder used before reconstitution. Objective Our aim was to assess the use of the Remote Food Photography Method to accurately estimate the weight of infant powdered formula before reconstitution among the standard serving sizes. Methods For each serving size (1 scoop, 2 scoops, 3 scoops, and 4 scoops), a set of seven test bottles and photographs were prepared as follow: recommended gram weight of powdered formula of the respective serving size by the manufacturer; three bottles and photographs containing 15%, 10%, and 5% less powdered formula than recommended; and three bottles and photographs containing 5%, 10%, and 15% more powdered formula than recommended (n=28). Ratio estimates of the test photographs as compared to standard photographs were obtained using standard Remote Food Photography Method analysis procedures. The ratio estimates and the US Department of Agriculture data tables were used to generate food and nutrient information to provide the Remote Food Photography Method estimates. Statistical analyses performed Equivalence testing using the two one-sided t tests approach was used to determine equivalence between the actual gram weights and the Remote Food Photography Method estimated weights for all samples, within each serving size, and within underprepared and overprepared bottles. Results For all bottles, the gram weights estimated by the Remote Food Photography Method were within 5% equivalence bounds with a slight underestimation of 0.05 g (90% CI −0.49 to 0.40; P Conclusions The maximum observed mean error was an overestimation of 1.58% of powdered formula by the Remote Food Photography Method under controlled laboratory conditions, indicating that the Remote Food Photography Method accurately estimated infant powdered formula.

To evaluate the feasibility of a brief, intensive weight loss intervention (IWL) to improve reproductive outcomes in obese subfertile women.Pilot study of IWL versus standard-of-care nutrition counseling (SCN).Single-site, academic institution.Obese women (body mass index, 35-45 kg/mWomen were rigorously prescreened to rule out secondary causes of subfertility. Eligible women were randomized to IWL or SCN. IWL consisted of 12 weeks of very-low-energy diet (800 kcal/day) + 4 weeks of a low-calorie conventional food-based diet (CFD) to promote 15% weight loss. SCN consisted of 16 weeks of CFD to promote ≥5% weight loss. Women were transitioned to weight maintenance diets and referred back to reproductive endocrinology for ovulation induction.Feasibility of recruitment, randomization, intervention implementation, and retention.Thirty-nine women were screened; 25 (64%) were eligible to participate, and 14 of those eligible (56%) agreed to be randomized, seven in each group. One withdrew from the IWL group and two from the SCN group. Percent weight loss was greater in the IWL group than in the SCN group (13% ± 5% vs. 4% ± 4%). Three of six women in the IWL group conceived and delivered term pregnancies. No pregnancies occurred in the SCN group.After rigorous screening, 44% of eligible women completed the study. IWL was associated with greater percentage weight loss and improvements in insulin sensitivity.NCT01894074.

BackgroundTwo-thirds of pregnant women exceed gestational weight gain (GWG) recommendations. Because excess GWG is associated with adverse outcomes for mother and child, development of scalable and cost-effective approaches to deliver intensive lifestyle programs during pregnancy is urgent. ObjectiveThe aim of this study was to decrease the proportion of women who exceed the Institute of Medicine (IOM) 2009 GWG guidelines. MethodsIn a parallel-arm randomized controlled trial, 54 pregnant women (age 18-40 years) who were overweight (n=25) or obese (n=29) were enrolled to test whether an intensive lifestyle intervention (called SmartMoms) decreased the proportion of women with excess GWG, defined as exceeding the 2009 IOM guidelines, compared to no intervention (usual care group). The SmartMoms intervention was delivered through mobile phone (remote group) or in a traditional in-person, clinic-based setting (in-person group), and included a personalized dietary intake prescription, self-monitoring weight against a personalized weight graph, activity tracking with a pedometer, receipt of health information, and continuous personalized feedback from counselors. ResultsA significantly smaller proportion of women exceeded the IOM 2009 GWG guidelines in the SmartMoms intervention groups (in-person: 56%, 10/18; remote: 58%, 11/19) compared to usual care (85%, 11/13; P=.02). The remote intervention was a lower cost to participants (mean US $97, SD $6 vs mean US $347, SD $40 per participant; P

We hypothesized that dietary monounsaturated fatty acids (MUFA) and exercise increase high-density lipoprotein cholesterol (HDL-C) by independent mechanisms, so there would be additive effects between a single, intensive session of exercise and high-MUFA ground beef on HDL-C and blood risk factors for cardiovascular disease. Seventeen postmenopausal women completed a 2-way crossover design in which they consumed five 114-g ground beef patties per week for two 6-week periods separated by a 4-week washout (habitual diet) period. The ground beef patties contained 21% total fat with either 9.97 (low-MUFA) or 12.72 (high-MUFA) g total MUFA. Blood was taken at entry, at the end of each 6-week diet period, after the 4-week washout period, and 24 hours after aerobic exercise sessions (75% VO₂peak, 2.07 MJ). After the ground beef intervention, the high-MUFA ground beef increased plasma palmitoleic acid and oleic acid, low-density lipoprotein (LDL) particle density, HDL-C, and HDL2b-C (all P < .05), whereas the low-MUFA ground beef increased LDL density. After the washout (habitual diet) period, the single exercise session increased serum LDL cholesterol, HDL-C, and HDL2a and decreased TAG and oleic acid. After the low-MUFA ground beef diet, exercise increased LDL size and HDL density and decreased LDL density and very low-density lipoprotein cholesterol, but had no effect on HDL-C fractions. After the high-MUFA ground beef intervention, exercise decreased palmitioleic acid, oleic acid, HDL-C, and HDL2a-C, but not HDL2b-C. Contrary to our hypothesis, the effects of exercise and a high-MUFA diet were not additive; instead, exercise attenuated the effects of the high-MUFA ground beef on HDL-C and plasma MUFAs. The differential effects of high-MUFA ground beef and exercise on HDL2a-C and HDL2b-C indicate that diet and exercise affect HDL-C by different mechanisms.

On the basis of previous results from this laboratory, this study tested the hypothesis that ground beef high in MUFA and low in SFA would increase the HDL-cholesterol (HDL-C) concentration and LDL particle diameter. In a crossover dietary intervention, 27 free-living normocholesterolemic men completed treatments in which five 114-g ground beef patties/wk were consumed for 5 wk with an intervening 4-wk washout period. Patties contained 24% total fat with a MUFA:SFA ratio of either 0.71 (low MUFA, from pasture-fed cattle) or 1.10 (high MUFA, from grain-fed cattle). High-MUFA ground beef provided 3.21 g more 18:1(n-9), 1.26 g less 18:0, 0.89 g less 16:0, and 0.36 g less 18:1(trans) fatty acids per patty than did the low-MUFA ground beef. Both ground beef interventions decreased plasma insulin and HDL(2) and HDL(3) particle diameters and increased plasma 18:0 and 20:4(n-6) (all P ≤ 0.05) relative to baseline values. Only the high-MUFA ground beef intervention increased the HDL-C concentration from baseline (P = 0.02). The plasma TG concentration was positively correlated with the plasma insulin concentration (r = 0.40; P0.001) and negatively correlated with HDL-C (r = -0.47; P0.001) and plasma 18:0 (r = -0.24; P0.01). Plasma insulin and HDL diameters were not correlated (r = 0.01; P0.50), indicating that reductions in these measures were not coordinately regulated. The data indicate that dietary beef interventions have effects on risk factors for cardiovascular disease that are independent (insulin, HDL diameters) and dependent (HDL-C) on beef fatty acid composition.