Near-Perfect Synaptic Integration by Nav1.7 in Hypothalamic Neurons Regulates Body Weight.

Neurons are well suited for computations on millisecond timescales, but some neuronal circuits set behavioral states over long time periods, such as those involved in energy homeostasis. We found that multiple types of hypothalamic neurons, including those that oppositely regulate body weight, are specialized as near-perfect synaptic integrators that summate inputs over extended timescales. Excitatory postsynaptic potentials (EPSPs) are greatly prolonged, outlasting the neuronal membrane time-constant up to 10-fold. This is due to the voltage-gated sodium channel Nav1.7 (Scn9a), previously associated with pain-sensation but not synaptic integration. Scn9a deletion in AGRP, POMC, or paraventricular hypothalamic neurons reduced EPSP duration, synaptic integration, and altered body weight in mice. In vivo whole-cell recordings in the hypothalamus confirmed near-perfect synaptic integration. These experiments show that integration of synaptic inputs over time by Nav1.7 is critical for body weight regulation and reveal a mechanism for synaptic control of circuits regulating long term homeostatic functions.

Reverse-translational identification of a cerebellar satiation network.

The brain is the seat of body weight homeostasis. However, our inability to control the increasing prevalence of obesity highlights a need to look beyond canonical feeding pathways to broaden our understanding of body weight control1-3. Here we used a reverse-translational approach to identify and anatomically, molecularly and functionally characterize a neural ensemble that promotes satiation. Unbiased, task-based functional magnetic resonance imaging revealed marked differences in cerebellar responses to food in people with a genetic disorder characterized by insatiable appetite. Transcriptomic analyses in mice revealed molecularly and topographically -distinct neurons in the anterior deep cerebellar nuclei (aDCN) that are activated by feeding or nutrient infusion in the gut. Selective activation of aDCN neurons substantially decreased food intake by reducing meal size without compensatory changes to metabolic rate. We found that aDCN activity terminates food intake by increasing striatal dopamine levels and attenuating the phasic dopamine response to subsequent food consumption. Our study defines a conserved satiation centre that may represent a novel therapeutic target for the management of excessive eating, and underscores the utility of a 'bedside-to-bench' approach for the identification of neural circuits that influence behaviour.

Biliopancreatic diversion for severe obesity: long-term weight maintenance and occurrence of nutritional complications are two facets of the same coin.

BACKGROUND: Despite the widespread clinical use of hypoabsorptive metabolic bariatric surgery, very long-term outcomes are still lacking. The aim of the study was to assess the long-term safety and efficacy of biliopancreatic diversion at 30 years in patients with class 3 obesity (BMI over 40 kg/m2). METHODS: This retrospective single-centre study used data from a prospectively collected database on a sample of consecutive patients submitted to biliopancreatic diversion with a minimum follow-up of 30 years. Outcomes assessed included overall survival, long-term weight loss and weight maintenance, remission of obesity-related co-morbidities, and short- and long-term surgical and/or nutritional or metabolic complications. RESULTS: Among 199 consecutive patients (136 female, 63 male) who had surgery between November 1992 and April 1994, the mean age at operation was 38 (range 14-69) years and mean preoperative BMI was 48.7 (32.0-74.3) kg/m2. At baseline, 91 of 199 patients (45.7%) had type 2 diabetes. At 20 and 30 years, 122 (61%) and 38 (19%) of the 199 patients respectively were available for follow-up. At 30 years, the overall mortality rate was 12% (23 of 199). Surgical complications were concentrated in the short-term follow-up, whereas nutritional or metabolic complications increased progressively over time. A nutritional complication was diagnosed in 73 of 122 patients (60%) at 20 years and 28 of 38 (74%) at 30 years. Weight loss and glycaemic control were maintained throughout the follow-up; mean % total weight loss was 32.8 (range 14.1-50.0) at 1 year and 37.7 (range 16.7-64.8) at 30 years. One patient presented with recurrence of type 2 diabetes at 20 and 30 years; there were no patients with new-onset type 2 diabetes. CONCLUSION: Biliopancreatic diversion leads to good and sustained weight maintenance up to 30 years with low perioperative risk, but at the cost of a high long-term prevalence of nutritional complications.

Discontinuing semaglutide after weight loss: strategy for weight maintenance and a possible new side effect.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) facilitate weight loss. Weight regain off therapy is concerning. We reported the case of a 35-year-old male prescribed oral semaglutide with 22.7 kg weight loss over 120 days. Herein, we describe the clinical course when discontinuing GLP-1 RA therapy, one approach to maintaining weight loss after discontinuation, and a possible new side effect. At day 120, we continued oral semaglutide 7 mg daily, down from 14 mg, for weight maintenance with subsequent weight regain. We re-increased semaglutide to 14 mg/day with weight re-loss within 1 month and weight maintance for a year. We then discontinued semaglutide; weight loss was maintained for 6 months. The patient reported lactose intolerance ∼13 months before starting semaglutide. During semaglutide therapy, the patient reported worsened lactose intolerance and new gluten intolerance. Food allergy/celiac testing were negative. Intolerances did not improve with semaglutide discontinuation. Six months after semaglutide discontinuation, the patient was diagnosed with small intestinal bacterial overgrowth, possibly worsened by semaglutide. Factors potentially supporting weight maintenance were early drug treatment for new-onset obesity, non-geriatric age, strength training, and diet modification. The case highlights tailoring approaches to maintain weight loss without GLP-1 RAs. Trials are needed to optimize weight maintenance strategies.

The relationship between psychological distress and weight maintenance in weight cycling: mediating role of eating behavior.

BACKGROUND: Obesity is a global public health concern. The goal of this study was to see if eating habits could mediate the relationship between psychological distress and weight maintenance in a population with a history of weight cycling. METHODS: A 3-month outpatient intervention consisting of a diet and exercise program was provided to 153 participants. Psychological distress, appetite, and behavior were assessed at the beginning and end of the study. Anthropometric measurements were taken at baseline and six months. RESULTS: After the structural equation model was developed, it was discovered that the psychological status of people with obesity and weight cycling histories correlated with the weight loss outcome effect (three and six months). This effect was mediated by factors related to eating behavior. Associative psychological factors had a direct effect on eating behavior (three months: ß = 0.181, 95% CI: 0.055-0.310; six months: ß = 0.182, 95% CI: 0.039-0.332) and appetite had a direct effect on eating behavior (three months: ß = 0.600, 95% CI: 0.514-0.717; six months: ß = 0.581, 95% CI: 0.457-0.713), both of which were significant (p < 0.01). At three months, psychological distress has a more substantial positive impact on weight change, with eating behavior acting as a partial mediator. At six months, there was no support for appetite's moderating role in eating behavior. CONCLUSIONS: The findings suggest that psychological interventions should be strengthened to improve weight loss effectiveness, particularly in participants with a history of weight cycling, making weight loss more complicated and prone to rebound. CLINICAL TRIAL REGISTRATION: The study has been registered in Clinical Trials (NCT05311462).

Factors predicting long-term weight maintenance in anorexia nervosa: a systematic review.

PURPOSE: Eating disorder recovery is a poorly defined concept, with large variations among researchers' definitions. Weight maintenance is a key aspect of recovery that remains relatively underexplored in the literature. Understanding the role of weight maintenance may help guide the development of treatments. This paper aims to address this by (1) investigating the factors predicting long-term weight maintenance in anorexia nervosa (AN) patients; (2) exploring differences in predictive factors between adolescent and adult populations; and (3) exploring how weight maintenance is conceptualised in the literature. METHODS: We conducted a systematic review following PRISMA guidelines to address our research questions. Five databases were searched and filtered according to our exclusion criteria. RESULTS: From the search, 1059 studies were yielded, and 13 studies were included for review. A range of weight, biological and psychological factors were found to predict weight maintenance among these papers. BMI at admission and discharge from inpatient treatment was the most common predictor among the papers. Few studies investigated biological factors and mixed evidence was found for psychological factors. We found no observable differences between adult and adolescent populations. Finally, weight maintenance was defined and measured differently across studies. CONCLUSION: This review's findings can help contribute to a well-rounded understanding of weight maintenance, and ultimately, of recovery. This can help support clinicians in tailoring interventions to improve long-term outcomes in AN. Future research should aim to replicate studies to better understand the relationship between the factors identified and weight maintenance. LEVEL I: Systematic review.

Clinician perspectives on patient-centered conversations about weight management with patients with early breast cancer.

BACKGROUND: The aim of this study is to gather detailed insights from breast cancer (BC) clinicians on how to have patient-centered conversations about weight and weight management with women diagnosed with early BC. A high body mass index (BMI) is a risk factor for female BC, and many women diagnosed with BC experience unhealthy weight gain after their primary treatment. The oncology team has the opportunity to discuss the importance of healthy weight for BC prognosis and survival. METHODS: The sample of community-based BC clinicians included the following: three Black clinicians, three White clinicians, and two clinicians who were neither Black nor White; six females and two males; and six MDs and two physician assistants or nurse practitioners. Semistructured telephone interviews were conducted with these clinicians regarding their experience with and insights into having healthy weight conversations during routine clinic visits. RESULTS: Clinicians noted that weight-related conversations should focus less on BMI and weight loss and more on "healthy behavior." Clinicians looked for cues from their patients as to when they were ready for "healthy weight" counseling, receptive to diet/nutrition counseling and referrals, and ready to attempt behavioral change. Clinicians noted that encouraging physical activity could be especially challenging with patients accustomed to a sedentary lifestyle. CONCLUSIONS: Clinic-based conversations about healthy weight are likely to be most productive for both patients and their treating oncologists during the post-primary treatment phase when patients are most receptive to behavioral change that enhances their prognosis and survival.

Exploratory analysis of reflective, reactive, and homeostatic eating behaviour traits on weight change during the 18-month NoHoW weight maintenance trial.

Behaviour change interventions for weight management have found varied effect sizes and frequent weight re-gain after weight loss. There is interest in exploring whether differences in eating behaviour can be used to develop tailored weight management programs. This secondary analysis of an 18-month weight maintenance randomised controlled trial (RCT) aimed to investigate the association between individual variability in weight maintenance success and change in eating behaviour traits (EBT). Data was analysed from the NoHoW trial (Scott et al., 2019), which was designed to measure processes of change after weight loss of ≥5% body weight in the previous year. The sample included 1627 participants (mean age = 44.0 years, SD = 11.9, mean body mass index (BMI) = 29.7 kg/m2, SD = 5.4, gender = 68.7% women/31.3% men). Measurements of weight (kg) and 7 EBTs belonging to domains of reflective, reactive, or homeostatic eating were taken at 4 time points up to 18-months. Increases in measures of 'reactive eating' (binge eating, p < .001), decreases in 'reflective eating' (restraint, p < .001) and changes in 'homeostatic eating' (unlimited permission to eat, p < .001 and reliance on hunger and satiety cues, p < .05) were significantly and independently associated with concomitant weight change. Differences in EBT change were observed between participants who lost, maintained, or re-gained weight for all EBTs (p < .001) except for one subscale of intuitive eating (eating for physical reasons, p = .715). Participants who lost weight (n = 322) exhibited lower levels of reactive eating and higher levels of reflective eating than participants who re-gained weight (n = 668). EBT domains can identify individuals who need greater support to progress in weight management interventions. Increasing reflective eating and reducing reactive eating may enhance weight management success.

Weight Management Treatment Representations: A Novel Use of the Common Sense Model.

We used the Common Sense Model to understand weight management treatment representations of diverse patients, conducting semistructured interviews with 24 veterans with obesity, recruited from multiple U.S. Veterans Health Administration facilities. We performed a directed content analysis to summarize representations and assess differences across demographic groups. Patients' representations were impacted by gender, socioeconomic status, and disability status, creating group differences in available treatment (e.g., disability-related limitations), negative consequences (e.g., expense), treatment timeline (e.g., men emphasized long-term lifestyle changes), and treatment models (e.g., women described medically driven models). Patients identified conventional representations aligning with medical recommendations and relating to positive consequences, long-term treatment timelines, and medically driven models. Finally, patients discussed risky representations, including undesirable attitudes related to short-term positive and negative consequences and long-term negative consequences. Applying the Common Sense Model emphasized diverse representations, influenced by patients' identities. Understanding representations may improve treatment to meet the needs of diverse preferences.

Informal Caregivers' Perceptions of Facilitators of Successful Weight Management for People With Spinal Cord Injury.

IMPORTANCE: Informal caregivers have valuable insights that occupational therapists can use to prevent and manage problems that may arise in people with spinal cord injury (SCI) because of a lack of physical activity and poor nutrition. OBJECTIVE: To assess caregiver-identified facilitators of weight management in people with SCI. DESIGN: Descriptive qualitative design using semistructured interviews and thematic analysis. SETTING: Regional SCI Care Model System and Veterans Health Administration. PARTICIPANTS: Informal caregivers (n = 24) of people with SCI. OUTCOMES AND MEASURES: Facilitators of successful weight management in care recipients with SCI. RESULTS: Four themes were identified as weight management facilitators: healthy eating (subthemes: food content, self-control, self-management, and healthy preinjury lifestyle), exercise and therapy (subthemes: occupational and physical therapy, receiving assistance, and resources for exercise), accessibility, and leisure activity or activities of daily living, the latter described as a source of activity (because of required energy expenditure) to facilitate weight management for people with more severe injuries. CONCLUSIONS AND RELEVANCE: These findings can inform the development of successful weight management plans by occupational therapists by incorporating feedback from informal caregivers. Because caregivers are involved in many of the facilitators identified, occupational therapists should communicate with the dyad about sourcing accessible places to increase physical activity and assessing in-person assistance and assistive technology needs to promote healthy eating and physical activity. Occupational therapists can use informal caregiver-identified facilitators of weight management to help prevent and manage problems for people with SCI secondary to limited activity and poor nutrition. What This Article Adds: Occupational therapy practitioners provide therapeutic intervention to people with SCI; this includes attention to weight management from the time of initial injury throughout their lives. This article is novel in the presentation of informal caregivers' perceptions about successful facilitators of weight management among people with SCI, which is important because caregivers are intimately involved in the daily activities of people with SCI and can be a liaison for occupational therapists and other health care providers about ways to facilitate healthy eating and physical activity.

Weight loss-induced improvement of body weight and insulin sensitivity is not amplified by a subsequent 12-month weight maintenance intervention but is predicted by adaption of adipose atrial natriuretic peptide system: 48-month results of a randomized controlled trial.

BACKGROUND: Behavioral weight loss interventions are frequently hampered by long-term inefficacy. As metabolic improvements and health-related quality of life (HRQoL) are diminished by weight regain, effective long-term strategies are highly desirable. We aimed to analyze whether an additional weight maintenance intervention could delay body weight regain and can induce a long-term improvement of metabolism and HRQoL for up to 48 months in humans. Given the short-term metabolic effects of natriuretic peptides (NP), we also investigated the role of the adipose atrial NP (ANP) system in this long-term context. METHODS: After a successful 12-week weight reduction program 143 subjects (age>18; BMI≥27 kg/m2) were randomized (1:1) to a control group or a 12-month multimodal weight maintenance intervention focusing on nutritional counseling and physical exercises. Secondary trial outcomes including course of BMI, HOMA-IR, glucose response after oGTT (glucoseAUC), and HRQoL (SF-36) were analyzed yearly for 48 months. Adipose ANP receptor mRNA expression was analyzed during weight loss. RESULTS: Initial weight loss (- 4.7±1.5 kg/m2) improved glucoseAUC, HOMA-IR, and HRQoL. Although BMI was still reduced after 48 months (-1.98 [95% CI -2.61, -1.35] kg/m2), benefits on HOMA-IR, glucoseAUC, and mental health disappeared after 36 (-0.49 [-1.00, 0.02]), 18 (0.61 [-9.57, 10.79] mg dl-1 min-1), and 18 months (2.06 [-0.08, 4.20]), respectively, while improved physical health persisted up to months 48 (2.95 [0.49, 5.40]). Weight maintenance intervention inhibited weight regain and delayed impairment of HOMA-IR and glucoseAUC (but not HRQoL) for up to 12 months. However, no metabolic long-term effect was seen beyond the intervention period. Lower adipose NPR-C and higher NPR-A mRNA expression after weight loss predicted smaller regain of weight (r=0.398; p<0.05)/fat mass (FM) (r=0.391; p<0.05) and longer improvement of HOMA-IR (r=-0.422; p<0.05), respectively. CONCLUSIONS: Additional benefits of a behavioral 12-month weight maintenance intervention after weight loss regarding body weight regain and metabolic improvement does not persist beyond the intervention period. However, weight loss-induced modulation of the adipose ANP system is probably involved in the long-term control of body weight regain and insulin sensitivity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00850629 . Registered on February 25, 2009.

The effects of a clinic-based weight loss program on health-related quality of life and weight maintenance in cancer survivors: A randomized controlled trial.

OBJECTIVE: The Healthy Living and Eating After Cancer Trial demonstrated that a clinic-based weight loss program reduced body weight, as compared with a waitlist control group, over 15 weeks. Here we report the impact of the weight loss intervention on health-related quality-of-life outcomes at week 15, and maintenance of weight loss to week 30. METHODS: This trial randomized cancer survivors of solid tumors and hematologic malignancies (breast cancer: 76.7%) to a 15-week group-based weight loss program (n = 30) or a waitlist control group (n = 30). Participants were not blinded to group assignment. Participants completed a variety of health-related quality-of-life outcome measures at baseline and week 15. From week 15 to week 30, participants initially randomized to the weight loss program were followed with no additional intervention, and participants initially randomized to the waitlist control group commenced the weight loss program. RESULTS: Over the 15 weeks, the weight loss program improved physical functioning (6.2 ± 2.9; p = 0.02; d = 0.31) and reduced insomnia symptoms (-17.1 ± 7.4; p = 0.03; d = -0.30) as measured by the EORTC QLQ-C30, and sleep disturbance (-4.9 ± 1.6; p = 0.005; d = -0.40) as measured by PROMIS, compared to waitlist control. After a weight loss of 4.6 ± 3.9 kg, from week 15 to week 30, participants who were initially randomized to the weight loss program maintained their prior weight loss (+0.6 ± 3.5 kg) and participants who were initially randomized to the waitlist control group lost weight (-3.4 ± 2.9 kg; p < 0.001). CONCLUSIONS: In cancer survivors with overweight or obesity, a 15-week clinic-based weight loss program improved health-related quality-of-life outcomes and produced sustained weight loss to week 30.

The impact of early body-weight variability on long-term weight maintenance: exploratory results from the NoHoW weight-loss maintenance intervention.

BACKGROUND: Weight-loss programmes often achieve short-term success though subsequent weight regain is common. The ability to identify predictive factors of regain early in the weight maintenance phase is crucial. OBJECTIVE: To investigate the associations between short-term weight variability and long-term weight outcomes in individuals engaged in a weight-loss maintenance intervention. METHODS: The study was a secondary analysis from The NoHoW trial, an 18-month weight maintenance intervention in individuals who recently lost ≥5% body weight. Eligible participants (n = 715, 64% women, BMI = 29.2 (SD 5.0) kg/m2, age = 45.8 (SD 11.5) years) provided body-weight data by smart scale (Fitbit Aria 2) over 18 months. Variability in body weight was calculated by linear and non-linear methods over the first 6, 9 and 12 weeks. These estimates were used to predict percentage weight change at 6, 12, and 18 months using both crude and adjusted multiple linear regression models. RESULTS: Greater non-linear weight variability over the first 6, 9 and 12 weeks was associated with increased subsequent weight in all comparisons; as was greater linear weight variability measured over 12 weeks (up to AdjR2 = 4.7%). Following adjustment, 6-week weight variability did not predict weight change in any model, though greater 9-week weight variability by non-linear methods was associated with increased body-weight change at 12 (∆AdjR2 = 1.2%) and 18 months (∆AdjR2 = 1.3%) and by linear methods at 18 months (∆AdjR2 = 1.1%). Greater non-linear weight variability measured over 12 weeks was associated with increased weight at 12 (∆AdjR2 = 1.4%) and 18 (∆AdjR2 = 2.2%) months; and 12-week linear variability was associated with increased weight at 12 (∆AdjR2 = 2.1%) and 18 (∆AdjR2 = 3.6%) months. CONCLUSION: Body-weight variability over the first 9 and 12 weeks of a weight-loss maintenance intervention weakly predicted increased weight at 12 and 18 months. These results suggest a potentially important role in continuously measuring body weight and estimating weight variability.

Cost-effectiveness of bariatric surgery and non-surgical weight management programmes for adults with severe obesity: a decision analysis model.

OBJECTIVES: To determine the most cost-effective weight management programmes (WMPs) for adults, in England with severe obesity (BMI ≥ 35 kg/m2), who are more at risk of obesity related diseases. METHODS: An economic evaluation of five different WMPs: 1) low intensity (WMP1); 2) very low calorie diets (VLCD) added to WMP1; 3) moderate intensity (WMP2); 4) high intensity (Look AHEAD); and 5) Roux-en-Y gastric bypass (RYGB) surgery, all compared to a baseline scenario representing no WMP. We also compare a VLCD added to WMP1 vs. WMP1 alone. A microsimulation decision analysis model was used to extrapolate the impact of changes in BMI, obtained from a systematic review and meta-analysis of randomised controlled trials (RCTs) of WMPs and bariatric surgery, on long-term risks of obesity related disease, costs, quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) measured as incremental cost per QALY gained over a 30-year time horizon from a UK National Health Service (NHS) perspective. Sensitivity analyses explored the impact of long-term weight regain assumptions on results. RESULTS: RYGB was the most costly intervention but also generated the lowest incidence of obesity related disease and hence the highest QALY gains. Base case ICERs for WMP1, a VLCD added to WMP1, WMP2, Look AHEAD, and RYGB compared to no WMP were £557, £6628, £1540, £23,725 and £10,126 per QALY gained respectively. Adding a VLCD to WMP1 generated an ICER of over £121,000 per QALY compared to WMP1 alone. Sensitivity analysis found that all ICERs were sensitive to the modelled base case, five year post intervention cessation, weight regain assumption. CONCLUSIONS: RYGB surgery was the most effective and cost-effective use of scarce NHS funding resources. However, where fixed healthcare budgets or patient preferences exclude surgery as an option, a standard 12 week behavioural WMP (WMP1) was the next most cost-effective intervention.

Teaching Medical Students to Help Patients Manage Their Weight: Outcomes of an Eight-School Randomized Controlled Trial.

BACKGROUND: Given the rising rates of obesity there is a pressing need for medical schools to better prepare students for intervening with patients who have overweight or obesity and for prevention efforts. OBJECTIVE: To assess the effect of a multi-modal weight management curriculum on counseling skills for health behavior change. DESIGN: A pair-matched, group-randomized controlled trial (2015-2020) included students enrolled in eight U.S. medical schools randomized to receive either multi-modal weight management education (MME) or traditional weight management education (TE). SETTING/PARTICIPANTS: Students from the class of 2020 (N=1305) were asked to participate in an objective structured clinical examination (OSCE) focused on weight management counseling and complete pre and post surveys. A total of 70.1% of eligible students (N=915) completed the OSCE and 69.3% (N=904) completed both surveys. INTERVENTIONS: The MME implemented over three years included a web-based course, a role-play classroom exercise, a web-patient encounter with feedback, and an enhanced clerkship experience with preceptors trained in weight management counseling (WMC). Counseling focused on the 5As (Ask, Advise, Assess, Assist, Arrange) and patient-centeredness. MEASUREMENTS: The outcome was student 5As WMC skills assessed using an objective measure, an OSCE, scored using a behavior checklist, and a subjective measure, student self-reported skills for performing the 5As. RESULTS: Among MME students who completed two of three WMC components compared to those who completed none, exposure was significantly associated with higher OSCE scores and self-reported 5A skills. LIMITATIONS: Variability in medical schools requiring participation in the WMC curriculum. CONCLUSIONS: This trial revealed that medical students struggle with delivering weight management counseling to their patients who have overweight or obesity. Medical schools, though restrained in adding curricula, should incorporate should incorporate multiple WMC curricula components early in medical student education to provide knowledge and build confidence for supporting patients in developing individualized plans for weight management. NIH TRIAL REGISTRY NUMBER: R01-194787.

Dietary Restraint Related to Body Weight Maintenance and Neural Processing in Value-Coding Areas in Adolescents.

BACKGROUND: There is an alarming increase in the obesity prevalence among children in an environment of increasing availability of preprocessed high-calorie foods. However, some people maintain a healthy weight even in such obesogenic environments. This difference in body weight management could be attributed to individual differences in dietary restraint; however, its underlying neurocognitive mechanisms in adolescents remain unclear. OBJECTIVES: This study aimed to elucidate these neurocognitive mechanisms in adolescents by examining the relationships between dietary restraint and the food-related value-coding region located in the ventromedial prefrontal cortex (vmPFC). METHODS: The association between dietary restraint and BMI was tested using a multilinear regression analysis in a large early adolescent cohort (n = 2554; age, 12.2 ± 0.3 years; BMI, 17.9 ± 2.5 kg/m2; 1354 boys). Further, an fMRI experiment was designed to assess the association between the vmPFC response to food images and dietary restraint in 30 adolescents (age, 17.6 ± 1.9 years; BMI, 20.7 ± 2.2 kg/m2; 13 boys). Additionally, using 54 individuals from the cohort (age, 14.5 ± 0.6 years; BMI, 18.8 ± 2.6 kg/m2; 31 boys), we assessed the association between dietary restraint and intrinsic vmPFC-related functional connectivity. RESULTS: In the cohort, adolescents with increased dietary restraint showed a lower BMI (ß = -0.38; P < 0.001; B = -0.06; SE = 0.003). The fMRI results showed a decreased vmPFC response to high-calorie food were correlated with greater dietary restraint. Moreover, there was an association of attenuated intrinsic vmPFC-related functional connectivity in the superior and middle frontal gyrus and the middle temporal gyrus with greater dietary restraint. CONCLUSIONS: Our findings suggest that dietary restraint in adolescents could be a preventive factor for weight gain; its effect involves modulating the vmPFC, which is associated with food value coding.

Weight and waist-to-hip ratio change pattern during the first five years of survival: data from a longitudinal observational Chinese breast cancer cohort.

BACKGROUND: Body weight management was an important component in breast cancer survivorship care. The present study described the change patterns of body weight and waist-to-hip ratio (WHR) during the first 5 years of survival, and investigated potential factors associated with very substantial changes. PATIENTS AND METHODS: Based on a longitudinal cohort with 1462 Chinese women with breast cancer, anthropometric measurements including body weight, height, waist and hip circumferences were measured by trained interviewers following standard protocol at four time-points: baseline at study entry, 18-, 36- and 60-months follow up assessments (termed as T0, T1, T2 and T3, respectively). Body height was measured at baseline and body weight at cancer diagnosis were retrieved from medical record. RESULTS: Compared to weight at breast cancer diagnosis, the median weight change was - 0.5 kg, 0 kg, + 0.5 kg, and + 1 kg at T0, T1, T2 and T3, respectively. During the first 5 years of survival, the proportion of women who were obese have slightly increased. At 60-months after diagnosis, only 14.3% of women had weight gain by > 5 kg; and the percentage of women who had weight gain by > 10% was 10.7%. Nearly half of patients had abdominal obesity at study entry, and this proportion were gradually increased to nearly 70% at 60-months follow-up. Multivariate analysis indicated that older age, and frequent sports participation during the first 5 years of survival were related to lower risk of very substantial weight gain (> 10%) at 60-month follow-up; patients aged 40-49 years, having ≥2 comorbidities and ER negative were associated with less likelihood of very substantial WHR substantial increase (> 10%) at 60-month follow-up. CONCLUSION: Weight gain was modest in Chinese breast cancer survivors during the first 5 years of survival, while central adiposity has become a contemporary public health issue. The incorporation of healthy weight and abdominal circumference patient education and management has a potential to improve cancer survivorship.

General and Eating Disorder Psychopathology in Relation to Short- and Long-Term Weight Change in Treatment-Seeking Children: A Latent Profile Analysis.

BACKGROUND: Concurrent general psychopathology (GP) and eating disorder psychopathology (EDP) are commonly reported among youth with overweight/obesity and may impact weight change. PURPOSE: We identified patterns of GP and EDP in children with overweight/obesity and examined the impact on weight change following family-based behavioral obesity treatment (FBT) and maintenance interventions. METHODS: Children (N = 172) participated in 4 month FBT and subsequent 8 month weight maintenance interventions. GP and EDP were assessed prior to FBT (baseline). Child percentage overweight was assessed at baseline, post-FBT (4 months), and post-maintenance (12 months). Latent profile analysis identified patterns of baseline GP and EDP. Linear mixed-effects models examined if profiles predicted 4- and 12-month change in percentage overweight and if there were two-way and three-way interactions among these variables, adjusting for relevant covariates. RESULTS: Results indicated a three-profile structure: lower GP and EDP (LOWER); subclinically elevated GP and EDP without loss of control (LOC; HIGHER); and subclinically elevated GP and EDP with LOC (HIGHER + LOC). Across profiles, children on average achieved clinically meaningful weight loss (i.e., ≥9 unit change in percentage overweight) from baseline to 4 month FBT and sustained these improvements at 12 month maintenance. There was no evidence that latent profiles were related to percentage overweight change from baseline to FBT (p > .05) or baseline to maintenance (p > .05). There was no evidence for two-way or three-way interactions (p > .05). CONCLUSION: Concurrent GP and EDP do not portend differential short- or long-term weight change following FBT and maintenance. Future research is warranted on the durability of weight change among youth with GP and EDP. TRIAL REGISTRATION: NCT00759746.

Post-weight loss changes in fasting appetite- and energy balance-related hormone concentrations and the effect of the macronutrient content of a weight maintenance diet: a randomised controlled trial.

PURPOSE: We investigated the effects of the macronutrient composition of diets with differing satiety values on fasting appetite-related hormone concentrations after weight loss and examined whether the hormone secretion adapted to changes in body fat mass (FM) and fat-free mass (FFM) during the weight maintenance period (WM). METHODS: Eighty-two men and women with obesity underwent a 7-week very-low-energy diet (VLED) and were then randomised to a higher-satiety food (HSF) group or a lower-satiety food (LSF) group during 24-weeks of the WM. The groups consumed isoenergetic foods with different satiety ratings and macronutrient compositions. RESULTS: During the WM, the HSF group consumed more protein and dietary fibre and less fat than the LSF group, but the groups showed similar changes in body weight and fasting appetite-related hormones. In the whole study sample, VLED induced 12 kg (p < 0.001) weight loss. At the end of the WM, weight regain was 1.3 kg (p = 0.004), ghrelin concentration increased, whereas leptin, insulin, and glucose concentrations decreased compared to pre-VLED levels (p < 0.001 for all). Peptide YY did not differ from pre-VLED levels. Changes in ghrelin levels were inversely associated with changes in FFM during weeks 0-12 of the WM (p = 0.002), while changes in leptin and insulin levels were positively associated with changes in FM during weeks 0-12 (p = 0.015 and p = 0.038, respectively) and weeks 12-24 (p < 0.001 and p = 0.022) of the WM. CONCLUSIONS: The macronutrient composition of an isoenergetic WM diet did not affect fasting appetite-related hormone concentrations. Leptin and insulin adjusted to the reduced FM, whereas ghrelin reflected FFM during the first months of the WM. TRIAL REGISTRATION: isrctn.com, ID 67529475.

An observational study on nutrition status in gastric cancer patients receiving ramucirumab plus taxane: BALAST study.

Limited data are available regarding the efficacy of nutrition support in advanced gastric cancer (AGC) patients receiving a standard second-line combination chemotherapy. The BALAST study is conducted as a prospective, multicenter observational study to evaluate the efficacy of nutrition support for patients with AGC treated with ramucirumab plus taxane as second-line treatment. As part of the routine care, patients who are malnourished or at risk of malnutrition will receive nutrition support from dietitians. We will enroll a total of 26 patients to estimate weight control rate at 12 weeks as primary end point. This study will generate valuable data reinforcing the role of nutrition support therapy for AGC patients receiving second-line chemotherapy.

Lay abstract Various guidelines recommend that nutrition support therapy should be considered if cancer patients are malnourished or at risk of malnutrition. Several studies have revealed that body weight loss, which is an important factor in determining the nutrition status, may predict survival during second-line standard chemotherapy with ramucirumab and a taxane for advanced gastric cancer (AGC) patients. However, limited data are available regarding the efficacy of nutrition support in AGC patients receiving ramucirumab and a taxane. This study is conducted as a prospective, multicenter observational study to evaluate the efficacy of nutrition support for Japanese patients with AGC treated with ramucirumab and a taxane. This study will generate valuable data reinforcing the role of nutrition support therapy for AGC patients in second-line treatment. Clinical trial registration: UMIN000037867.