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Sedentary behaviors (SB) after cancer diagnosis are associated with poor prognosis for certain cancers, and cancer patients and survivors report high levels of SB. Reducing SB may be a feasible and effective intervention strategy to improve outcomes. This systematic review aims to identify and evaluate the literature on interventions to reduce SB in cancer patients and survivors.Studies were identified via database searches in December 2020. Two authors evaluated study eligibility. Data were extracted and checked, and risk of bias was assessed by the study team. Of 1401 records identified, nine studies involving 394 cancer patients or survivors were included in this review. Six were randomized trials, three were non-randomized intervention studies, and almost all (n = 8) focused on feasibility with small sample sizes. All studies were conducted within the previous 5 years in Canada, Australia, USA, and South Korea. Cancer types studied were breast (n = 3), prostate (n = 2), colorectal or peritoneal (n = 1), and mixed types (n = 3). Intervention duration of 12 weeks was most common (n = 7). Five studies had multiple intervention components, and six studies included wearable devices to measure and/or prompt behavior change. There was an overall trend where intervention groups reduced SB vs. control groups, often coupled with an increase in moderate-to-vigorous physical activity. This review suggests that there is some promise for intervention strategies to reduce SB in cancer patients and survivors. There is a need for more high-quality randomized controlled trials to understand how to best decrease SB in cancer patients and survivors.

This study examined associations between BMI and dietary sugar intake with sucrose-induced fibroblast growth factor 21 (FGF21) and whether circulating FGF21 is associated with brain signaling following sucrose ingestion in humans.A total of 68 adults (29 male; mean [SD), age 23.2 [3.8] years; BMI 27.1 [4.9] kg/mHigher circulating FGF21 levels were associated with reduced blood flow in the striatum in response to sucrose (β = -7.63, p = 0.03). This association was greatest among persons with healthy weight (β = -15.70, p = 0.007) and was attenuated in people with overweight (β = -4.00, p = 0.63) and obesity (β = -12.45, p = 0.13). BMI was positively associated with FGF21 levels in response to sucrose (β = 0.53, p = 0.02). High versus low dietary sugar intake was associated with greater FGF21 responses to acute sucrose ingestion in individuals with healthy weight (β = 8.51, p = 0.04) but not in individuals with overweight or obesity (p0.05).These correlative findings support evidence in animals showing that FGF21 acts on the brain to regulate sugar consumption through a negative feedback loop.

OBJECTIVE This study investigated whether brain regions involved in the regulation of food intake respond differently to glucose ingestion in children and adults and the relationship between brain responses and weight status. METHODS Data included 87 children (ages 7-11 years) and 94 adults (ages 18-35 years) from two cohorts. Healthy weight, overweight, and obesity were defined by Centers for Disease Control and Prevention criteria. Brain responses to glucose were determined by measuring cerebral blood flow using arterial spin labeling magnetic resonance imaging in brain regions involved in the regulation of eating behavior. RESULTS Children showed significantly larger increases in brain responses to glucose than adults in the dorsal striatum (p < 0.01), insula (p < 0.01), hippocampus (p < 0.01), and dorsal-lateral prefrontal cortex (p < 0.01). Responses to glucose in the dorsal striatum (odds ratio [OR] = 1.52, 95% CI 1.05-2.20; p = 0.03), hippocampus (OR = 1.51, 95% CI: 1.02-2.22; p = 0.04), insula (OR = 1.64, 95% CI: 1.11-2.42; p = 0.01), and orbitofrontal cortex (OR = 1.63 95% CI: 1.12-2.39; p = 0.01) were positively associated with overweight or obesity, independent of age group. CONCLUSIONS Children have greater brain responses to glucose ingestion than adults in regions involved in eating behavior, and these responses are associated with weight status.

Anthracycline chemotherapy is a frequent treatment for breast cancer, whereas it can increase risk of physiologic side-effects, such as metabolic syndrome (MetS). Exercise has been used as a non-pharmacological strategy to decrease MetS. Specifically, high-intensity interval training (HIIT) has been shown to improve MetS in patients with diabetes or cardiac rehabilitation patients; however, the effects of HIIT on MetS and associated biomarkers in patients with breast cancer receiving anthracycline chemotherapy have not been previously explored. Therefore, we purposed to determine the effects of HIIT on MetS in breast cancer patients undergoing anthracycline chemotherapy.In total, 30 patients with breast cancer were recruited prior to initiating treatment and randomized into HIIT (n = 15) or control (n = 15). The HIIT group attended supervised cycling sessions 3 days/week for 8 weeks. MetS was assessed by waist circumference, blood pressure, fasting levels of high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose. Circulating levels of MetS-related biomarkers were also measured (total cholesterol, insulin, HbA1c, leptin, adiponectin, and c-reactive protein).After 8 weeks, MetS z-score was significantly improved in the HIIT group compared with controls (-7.60, 95% CI: -9.08 to -6.13, p 0.001). MetS variables (HDL-C, glucose, and triglycerides) and circulating levels of MetS-related biomarkers were significantly improved in the HIIT group compared with controls (p 0.001). Non-significant differences were found in body composition outcomes at the end of the study.HIIT may be an effective strategy to improve MetS in breast cancer patients undergoing anthracycline chemotherapy. Furthermore, changes in MetS were independent of changes in body composition.

Evidence suggests that insulin resistance (IR) affects feeding behavior by modulating neural responses to post-ingestive signals, including nutrients and taste. We examined associations between IR and activation of the hypothalamus and insula, brain regions involved in homeostasis and taste processing, to ingestion of sugars and the non-nutritive sweetener (NNS) , sucralose. Seventy-four participants (23.4±4 years; 42%male; BMI 27.2±5; HOMA-IR 5.3±5) completed 4 MRI visits with ingestion of drinks containing 75g sucrose, 75g glucose, sucralose, or water in a randomized cross-over design. Arterial spin labeling MRI was performed before, 15min and 30min after drink ingestion to measure cerebral blood flow (CBF) . Primary outcomes were associations between HOMA-IR and hypothalamic and insular CBF responses to glucose vs. sucrose, sucralose vs. water, and sucrose vs. sucralose. Mixed effects models included the following factors: drink contrasts, sex, time point, and BMI and HOMA-IR as continuous variables. Bonferroni-Holm was used to adjust for multiple comparisons. In the hypothalamus, HOMA-IR, independent of BMI, was associated with a greater hypothalamic CBF response to sucralose vs. water (p Disclosure S. Kullmann: Other Relationship; Novo Nordisk. R. Veit: None. K. Jann: None. S.H. Luo: None. B.C. Angelo: None. J.M. Alves: None. J.R. Monterosso: None. K.A. Page: None. Funding NIDDK R01DK102794

Key Points Question Are adiposity and sex associated with neural, metabolic, and behavioral responses to consumption of nonnutritive sweeteners (NNSs) vs nutritive sugar? Findings In this randomized crossover trial, both obesity and female sex were associated with differential neural food cue responsivity in reward processing areas following ingestion of sucralose (an NNS) compared with sucrose (nutritive sugar). Meaning These findings suggest that female individuals and those with obesity have greater neural reward responses to NNS vs nutritive sugar consumption, highlighting the need to consider individual biological factors that might influence the efficacy of NNS., This randomized crossover trial examines neural reactivity to different types of high-calorie food cues, metabolic responses, and eating behavior following sucralose vs sucrose consumption among healthy young adults., Importance Nonnutritive sweeteners (NNSs) are used as an alternative to nutritive sweeteners to quench desire for sweets while reducing caloric intake. However, studies have shown mixed results concerning the effects of NNSs on appetite, and the associations between sex and obesity with reward and appetitive responses to NNS compared with nutritive sugar are unknown. Objective To examine neural reactivity to different types of high-calorie food cues (ie, sweet and savory), metabolic responses, and eating behavior following consumption of sucralose (NNS) vs sucrose (nutritive sugar) among healthy young adults. Design, Setting, and Participants In a randomized, within-participant, crossover trial including 3 separate visits, participants underwent a functional magnetic resonance imaging task measuring blood oxygen level–dependent signal in response to visual cues. For each study visit, participants arrived at the Dornsife Cognitive Neuroimaging Center of University of Southern California at approximately 8:00 am after a 12-hour overnight fast. Blood was sampled at baseline and 10, 35, and 120 minutes after participants received a drink containing sucrose, sucralose, or water to measure plasma glucose, insulin, glucagon-like peptide(7-36), acyl-ghrelin, total peptide YY, and leptin. Participants were then presented with an ad libitum meal. Participants were right-handed, nonsmokers, weight-stable for at least 3 months before the study visits, nondieters, not taking medication, and with no history of eating disorders, illicit drug use, or medical diagnoses. Data analysis was performed from March 2020 to March 2021. Interventions Participants ingested 300-mL drinks containing either sucrose (75 g), sucralose (individually sweetness matched), or water (as a control). Main Outcomes and Measures Primary outcomes of interest were the effects of body mass index (BMI) status and sex on blood oxygen level–dependent signal to high-calorie food cues, endocrine, and feeding responses following sucralose vs sucrose consumption. Secondary outcomes included neural, endocrine, and feeding responses following sucrose vs water and sucralose vs water (control) consumption, and cue-induced appetite ratings following sucralose vs sucrose (and vs water). Results A total of 76 participants were randomized, but 2 dropped out, leaving 74 adults (43 women [58%]; mean [SD] age, 23.40 [3.96] years; BMI range, 19.18-40.27) who completed the study. In this crossover design, 73 participants each received water (drink 1) and sucrose (drink 2), and 72 participants received water (drink 1), sucrose (drink 2), and sucralose (drink 3). Sucrose vs sucralose was associated with greater production of circulating glucose, insulin, and glucagon-like peptide–1 and suppression of acyl-ghrelin, but no differences were found for peptide YY or leptin. BMI status by drink interactions were observed in the medial frontal cortex (MFC; P for interaction < .001) and orbitofrontal cortex (OFC; P for interaction = .002). Individuals with obesity (MFC, β, 0.60; 95% CI, 0.38 to 0.83; P

Fibroblast growth factor 21 (FGF21) is a liver-derived hormone that regulates energy homeostasis. In humans, few studies have investigated whether FGF21 may act to suppress sugar intake and influence eating behavior, and the effects of adiposity on post-ingestive FGF21 regulation of appetite are unknown. Here, we demonstrate among two cohorts of healthy, young adults that acute oral fructose and sucrose compared to glucose lead to greater circulating FGF21. Moreover, high compared to low dietary added sugar intake is associated with greater sucrose-stimulated FGF21 among participants with healthy weight but attenuated in people with overweight and obesity. In addition, our study is the first to demonstrate associations between circulating FGF21 and neural signaling following an acute sucrose load among humans with healthy weight. Collectively, our results suggest that these potential compensatory relationships between sucrose-stimulated circulating FGF21, habitual sugar intake, and post-ingestive brain responses may be altered among adults with overweight and obesity.Significance StatementAnimal models have established FGF21 as an autoregulator of sweet consumption, but few studies have examined post-ingestive FGF21 effects in humans. In this report, we demonstrate a compensatory relationship between sucrose-stimulated FGF21 and high dietary added sugar intake through a potential liver-to-brain negative-feedback cycle among healthy, young adults. Notably, our findings also suggest that humans with overweight and obesity may have altered FGF21 neuroendocrine signaling.

We investigated how emotional responses (positive and negative affect), physical activity (PA), and sedentary behaviors related to anxiety among US children during the COVID-19 pandemic. Sixty-four typically-developing children (63% girls) age 9-15 years old completed two virtual visits during height of "stay-at-home" measures between April 22 - July 29, 2020. Children completed 24-hour PA recalls, state portion of State-Trait Anxiety Inventory for Children (STAIC), and the shortened 10-item Positive and Negative Affect Schedule for Children (PANAS-C). Children reported state anxiety scores that were more than 5 standard deviations greater than values from healthy pediatric populations prior to the pandemic. Children with higher positive affect and who reported more time in PA reported less state anxiety. Sedentary and leisure screen time were positively correlated with negative affect. Our findings suggest that maintaining positive affect, engaging in PA, and limiting leisure screen time may be important for child mental health during stressful periods.There is increasing concern regarding how the COVID-19 pandemic may impact the psychological and physical health of children. To date, studies on mental health during the pandemic in children are limited. We investigated links between activity levels and psychological outcomes in children during the height of the "stay-at-home" measures. We found that children had anxiety scores that were more than 5 standard deviations greater than normative values from healthy pediatric populations prior to the pandemic, and 94% of children exceeded the American Academy of Pediatrics recommendations on leisure screen time. Positive affect and physical activity were associated with reduced anxiety levels in children during the pandemic. These findings highlight the important mental health benefits of maintaining positive affect, engaging in physical activity, and limiting leisure screen time for children, especially during stressful periods.

Background The coronavirus disease 2019 (COVID-19) is associated with adverse child mental health outcomes and reduced physical activity. Moreover, prenatal exposure to gestational diabetes (GDM) is associated with increased risk for adverse psychological outcomes in children. Objectives Assess prenatal exposure to GDM on anxiety levels and physical activity in children during the COVID-19 pandemic. Methods Sixty-five children age 9 to 15 reported their physical activity and anxiety levels using the 24-hours physical activity recall and the State-Trait Anxiety Inventory for Children via phone or video meetings. Prenatal exposure to GDM was obtained from maternal electronic medical records. Results The 38 GDM-exposed children reported significantly higher anxiety levels and were less likely to engage in any vigorous physical activity (VPA) (5% vs 30%) compared to the 27 GDM-unexposed children. Lower levels of physical activity were significantly associated with higher levels of anxiety. Less engagement in VPA explained 75% of the association between GDM exposure and anxiety levels. Conclusions Engaging in physical activity during the COVID-19 pandemic may be beneficial for reducing anxiety, particularly amongst GDM-exposed children.

We investigated how emotional responses (positive and negative affect), physical activity (PA), and sedentary behaviors related to anxiety among US children during the COVID-19 pandemic. Sixty-four typically-developing children (63% girls) age 9-15 years old completed two virtual visits during height of “stay-at-home” measures between April 22 – July 29, 2020. Children completed 24-hour PA recalls, state portion of State-Trait Anxiety Inventory for Children (STAIC), and the shortened 10-item Positive and Negative Affect Schedule for Children (PANAS-C). Children reported state anxiety scores that were more than 5 standard deviations greater than values from healthy pediatric populations prior to the pandemic. Children with higher positive affect and who reported more time in PA reported less state anxiety. Sedentary and leisure screen time were positively correlated with negative affect. Our findings suggest that maintaining positive affect, engaging in PA, and limiting leisure screen time may be important for child mental health during stressful periods.Statement of RelevanceThere is increasing concern regarding how the COVID-19 pandemic may impact the psychological and physical health of children. To date, studies on mental health during the pandemic in children are limited. We investigated links between activity levels and psychological outcomes in children during the height of the “stay-at-home” measures. We found that children had anxiety scores that were more than 5 standard deviations greater than normative values from healthy pediatric populations prior to the pandemic, and 94% of children exceeded the American Academy of Pediatrics recommendations on leisure screen time. Positive affect and physical activity were associated with reduced anxiety levels in children during the pandemic. These findings highlight the important mental health benefits of maintaining positive affect, engaging in physical activity, and limiting leisure screen time for children, especially during stressful periods.

Background/Objectives: With rising obesity rates among pregnant women, more children are exposed in utero to maternal obesity. In prior epidemiological studies, exposure to maternal obesity was associated with lower intelligence quotient (IQ) scores and worse cognitive abilities in offspring. Further studies have shown that offspring exposed to maternal obesity, exhibit differences in the white matter microstructure properties, fractional anisotropy (FA) and mean diffusivity (MD). In contrast, physical activity was shown to improve cognition and white matter microstructure during childhood. We examined if child physical activity levels modify the relationship between prenatal exposure to maternal obesity with IQ and white matter microstructure in offspring. Subjects/Methods: One hundred children (59% girls) age 7–11 years underwent brain magnetic resonance imaging and IQ testing. Maternal pre-pregnancy BMI was abstracted from electronic medical records. White matter was assessed using diffusion tensor imaging with the measures, global FA, MD. The 3-day physical activity recall was used to measure moderate-to-vigorous physical activity and vigorous physical activity (VPA). Linear regression was used to test for interactions between prenatal exposure to maternal overweight/obesity and child PA levels on child IQ and global FA/MD. Results: The relationship between prenatal exposure to maternal overweight/obesity and child IQ and global FA varied by child VPA levels. Children exposed to mothers with overweight/obesity who engaged in more VPA had higher IQ scores and global FA compared to exposed children who engaged in less VPA. Associations were independent of child age, sex, BMI Z-score and socioeconomic status. Children born to normal-weight mothers did not differ in either IQ or global FA by time in VPA. Conclusions: Our findings support findings in rodent models and suggest that VPA during childhood modifies the relationship between prenatal exposure to maternal obesity and child IQ and white matter microstructure.

Research goalAssess the relationships between anxiety levels, physical activity and in utero exposure to Gestational Diabetes mellitus (GDM) in children age 9 to 15, during the coronavirus disease 2019 (COVID-19) pandemic.MethodsDuring the COVID-19 pandemic, participants completed phone call or video calls with study personnel where they were asked to report on their physical activity and anxiety levels using the 24-hour physical activity recall and the State-Trait Anxiety Inventory for Children. GDM-exposure was assessed using electronic medical records.ResultsChildren who reported higher levels of moderate to vigorous physical activity or vigorous physical activity, reported lower anxiety symptoms. Children exposed to GDM in utero reported higher anxiety scores and lower engagement in vigorous physical activity compared to unexposed children. Moreover, the pathway through which children exposed to GDM in utero, reported higher anxiety was partially explained by reduced engagement in vigorous physical activity (75%, p=0.05).ConclusionsEngaging in physical activity during the COVID-19 pandemic may be beneficial for reducing anxiety, particularly among children exposed to GDM in utero, who are at increased risk for adverse psychological outcomes.

Prenatal exposure to maternal obesity is linked to neurocognitive deficits in offspring. In contrast, engaging in physical activity (PA) is beneficial for cognition and brain development. We aimed to determine if greater PA is associated with higher intelligence quotient (IQ) scores and greater brain white matter integrity in children born to mothers with a range of pre-pregnancy BMI. Ninety-nine children (59 girls) ages 7-13 years completed the study. Maternal pre-pregnancy BMI was obtained from electronic medical records. Wechsler Abbreviated Scale of Intelligence was used to measure IQ. Diffusion tensor imaging was used to measure mean global fractional anisotropy (FA), a marker of white matter integrity. Time spent in moderate-to-vigorous PA (MVPA) and vigorous PA (VPA) was assessed using 3-day PA recalls. Linear regressions were used to assess whether maternal pre-pregnancy BMI or child MVPA and VPA were associated with child IQ scores and global FA. Maternal pre-pregnancy BMI ranged from 19.0-54.0 kg/m2 (43% obese). Mean±SD child IQ was 106.4±14.0, MVPA was 132.8±95.4 min/day, and VPA was 19.0±27.1 min/day. Maternal pre-pregnancy BMI was negatively associated with child IQ scores (β=-0.31; p=0.10); this marginal association remained after adjusting for child age, sex, puberty, BMI z-score, and socioeconomic status (β=-0.42; p=0.095). MVPA was not associated with child IQ (β=2.63; p=0.16). However, children who spent more time in VPA had higher IQ scores before (β=7.05; p=0.003) and after adjusting for the same co-variates (β=5.65; p=0.024) and further adjusting for maternal pre-pregnancy BMI (β=5.01; p=0.049). Children who spent more time in VPA also had greater mean global FA (unadjusted: β=0.01; p=0.017; adjusted: β=0.01; p=0.005). These findings suggest that engaging in VPA is beneficial for cognition and white matter microstructure in children, independent of maternal pre-pregnancy BMI. Disclosure J. Alves: None. B.C. Angelo: None. S.H. Luo: None. T. Chow: None. A.G. Yunker: None. A. Xiang: None. K.A. Page: None. J. Zink: None. B.R. Belcher: None. K. Clark: None. Funding American Diabetes Association (1-14-ACE-36 to K.A.P.); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116858); National Institute of Mental Health (F31MH115640)

The hypothalamus has an abundant expression of sweet taste receptors that play a role in glucose sensing and energy homeostasis. Evidence suggests that liking “sweets” can be associated with weight gain, but the influence of sweet taste preference (STP) on hypothalamic regulation of appetite is unknown. We tested the hypothesis that STP is associated with increased hypothalamic activation in response to glucose (a potential marker of obesity risk), and that greater STP and glucose-linked hypothalamic activation would predict greater weight gain. Forty-six (24 female) adults age 18-35 years completed the study. Height and weight were measured at baseline and 6-12 months later in a subset of 38. STP was assessed via the Monell 2-series, forced-choice tracking procedure. Arterial spin labeling magnetic resonance imaging was performed before and ∼35 min after 75g glucose ingestion, and hypothalamic response to glucose was measured by calculating hypothalamic blood flow (BF) after minus before glucose ingestion. Linear regression was used to examine relationships between STP and the hypothalamic response to glucose and changes in BMI before and after adjusting for age, sex, BMI, mean cerebral BF, and baseline BMI. Baseline BMI was 27.61±5.13 kg/m2. STP scores ranged from 3% to 29.39% w/v. The hypothalamic response to glucose ranged from -14.64 to 15.63 ml/100g/min. Change in BMI ranged from -2.93 to 6.00 kg/m2. STP was positively associated with hypothalamic response to glucose (unadjusted: β=0.65, p Disclosure A.G. Yunker: None. J. Alves: None. B.C. Angelo: None. A.W. DeFendis: None. S.H. Luo: None. K.A. Page: None. Funding National Institutes of Health (R01DK102794)

In rodent literature, there is evidence that excessive fructose consumption during development has a detrimental impact on hippocampal structure and function. In this study of 103 children ages 7&ndash, 11 years old, we investigated whether dietary fructose intake was related to alterations in hippocampal volume and connectivity in humans. To examine if these associations were specific to fructose or were related to dietary sugars intake in general, we explored relationships between dietary intake of added sugars and the monosaccharide, glucose, on the same brain measures. We found that increased dietary intake of fructose, measured as a percentage of total calories, was associated with both an increase in the volume of the CA2/3 subfield of the right hippocampus and increased axial, radial, and mean diffusivity in the prefrontal connections of the right cingulum. These findings are consistent with the idea that increased fructose consumption during childhood may be associated with an inflammatory process, and/or decreases or delays in myelination and/or pruning. Increased habitual consumption of glucose or added sugar in general were associated with an increased volume of right CA2/3, but not with any changes in the connectivity of the hippocampus. These findings support animal data suggesting that higher dietary intake of added sugars, particularly fructose, are associated with alterations in hippocampal structure and connectivity during childhood.