New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics.

Nearly half of Americans are projected to have obesity by 2030, underscoring the pressing need for effective treatments. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) represent the first agents in a rapidly evolving, highly promising landscape of nascent hormone-based obesity therapeutics. With the understanding of the neurobiology of obesity rapidly expanding, these emerging entero-endocrine and endo-pancreatic agents combined or coformulated with GLP-1 RAs herald a new era of targeted, mechanism-based treatment of obesity. This article reviews GLP-1 RAs in the treatment of obesity and previews the imminent future of nutrient-stimulated hormone-based anti-obesity therapeutics.

Addressing psychosocial health in the treatment and care of adolescents with obesity.

Obesity affects 158 million youth worldwide and is associated with psychosocial comorbidity. This review describes weight management options utilized by adolescents, including both self-directed weight loss and medically supervised obesity treatment interventions, and associated psychosocial impacts. A majority of adolescents with obesity attempt to manage weight on their own, primarily through attempting weight loss, sometimes with supplement use. Approaches such as these are associated with a degree of risk, disordered eating behaviors, and further weight gain. In contrast, medically supervised multicomponent interventions are associated with improved psychosocial health, including quality of life, self-esteem, and body image, and reduced symptoms of depression, anxiety, and eating disorders. Few studies utilizing antiobesity pharmacotherapy have reported psychosocial outcomes, and trials of bariatric surgery show some early improvements with a need for sustained psychological support following surgery. Greater access to medically supervised treatment services is required to facilitate obesity care for adolescents. Early data on psychosocial health and obesity treatment offer promising outcomes; however, larger randomized controlled trials and longer-term data are needed. Future research should include both physiological and psychosocial outcomes to assess impact of interventions on the holistic health of adolescents with obesity.

Dietary supplements and alternative therapies for obesity: A Perspective from The Obesity Society's Clinical Committee.

In this Perspective Statement from The Obesity Society, the Clinical Committee discusses the use of weight loss supplements in the United States and the lack of regulatory oversight and rigorous testing of their efficacy and safety. A number of products and services claiming to promote weight loss are directly marketed to individuals with obesity and those wanting to lose weight. These products are not regulated as "drugs" by the Federal Drug Administration but, rather, are treated as dietary supplements if ingredients are "generally regarded as safe," requiring little or no testing to show efficacy or safety. Health care providers should be aware of the lack of evidence and deficiencies in regulatory oversight of dietary supplements marketed for weight loss. Regulatory authorities should protect consumers by ensuring accurate and safe marketing claims and preventing promotion of unproven and potentially unsafe products and claims.

Mindfulnes-Based Stress Reduction for Older Couples with Metabolic Syndrome: a Pilot Randomized Controlled Trial.

OBJECTIVE: We examined the feasibility and explored the physical, psychological, relational, and biological effects of Mindfulness-Based Stress Reduction (MBSR), an 8-week standardized mindfulness program, involving older married couples (60 years or older) with metabolic syndrome (one or both partners had metabolic syndrome). We also explored gender differences. METHODS: A pilot randomized controlled trial (RCT) compared MBSR to a Wait List Control (WLC) arm at baseline, post-intervention, and 3-month follow-up clinic visits. Twenty-two spouses (11 couples) self-reported stress, physical and mental functioning, mindfulness, and relationship satisfaction at each time point. Fasting glucose, cholesterol, triglycerides, blood pressure, weight, and waist circumference were measured. MBSR couples answered questions about partner influences on participation, adherence, and practice at the post-intervention visit. RESULTS: In terms of adherence to MBSR sessions, four of the six couples attended all 10 sessions; one couple attended 7; and one wife attended 6 and her husband attended 5 sessions. In terms of efficacy, there were no significant intervention effects; however, there were significant gender by intervention effects. Pre- to post-intervention, MBSR wives displayed greater increases in physical functioning (ß = 1.18, t(36) = 3.17, p = .003) and relationship satisfaction (ß = .72, t(36) = 2.81, p = .007) than WLC wives. Effects for husbands were not significant. Qualitatively, participants reported encouragement and increased relationship closeness. CONCLUSIONS: Engaging in MBSR as a couple to address symptoms of metabolic syndrome was well-received and feasible. Preliminary effects suggest more benefits for wives than husbands in terms of physical functioning and relational well-being.

Preventing Childhood Obesity Through a Mindfulness-Based Parent Stress Intervention: A Randomized Pilot Study.

OBJECTIVE: To assess the feasibility of engaging stressed, low-income parents with obesity in a novel mindfulness-based parent stress intervention aimed at decreasing the risk of early childhood obesity. STUDY DESIGN: An 8-week mindfulness-based parent stress group intervention (parenting mindfully for health) plus nutrition and physical activity counseling (PMH+N) was developed for parents with obesity aimed at preventing obesity in their at-risk 2- to 5-year-old children. PMH+N was compared with a control group intervention (C+N), and improvement in parenting was assessed before and after the intervention using the laboratory-based toy wait task (TWT). In addition, nutrition, physical activity, and stress were assessed using a multimethod approach. RESULTS: After establishing feasibility in 20 parent-child dyads (phase 1), 42 dyads were randomized to PMH+N vs C+N (phase 2). Compared with the C+N group, the PMH+N group demonstrated significantly better group attendance (P < .015), greater improvement in parental involvement (P < .05), and decreased parental emotional eating rating (P < .011). Furthermore, C+N, but not PMH+N, was associated with significant increases in child body mass index percentile during treatment (P < .03) when accounting for the TWT before and after changes in parenting scores. CONCLUSIONS: These findings suggest that a mindfulness-based parent stress intervention to decrease childhood obesity risk is feasible, requires further testing of therapeutic mechanisms in larger samples, and may be a potential way to attenuate the risk of childhood obesity. TRIAL REGISTRATION: ClinicalTrials.govNCT01974102.

Functional Connectivity During Exposure to Favorite-Food, Stress, and Neutral-Relaxing Imagery Differs Between Smokers and Nonsmokers.

INTRODUCTION: Tobacco-use disorder is a complex condition involving multiple brain networks and presenting with multiple behavioral correlates including changes in diet and stress. In a previous functional magnetic resonance imaging (fMRI) study of neural responses to favorite-food, stress, and neutral-relaxing imagery, smokers versus nonsmokers demonstrated blunted corticostriatal-limbic responses to favorite-food cues. Based on other recent reports of alterations in functional brain networks in smokers, the current study examined functional connectivity during exposure to favorite-food, stress, and neutral-relaxing imagery in smokers and nonsmokers, using the same dataset. METHODS: The intrinsic connectivity distribution was measured to identify brain regions that differed in degree of functional connectivity between groups during each imagery condition. Resulting clusters were evaluated for seed-to-voxel connectivity to identify the specific connections that differed between groups during each imagery condition. RESULTS: During exposure to favorite-food imagery, smokers versus nonsmokers showed lower connectivity in the supramarginal gyrus, and differences in connectivity between the supramarginal gyrus and the corticostriatal-limbic system. During exposure to neutral-relaxing imagery, smokers versus nonsmokers showed greater connectivity in the precuneus, and greater connectivity between the precuneus and the posterior insula and rolandic operculum. During exposure to stress imagery, smokers versus nonsmokers showed lower connectivity in the cerebellum. CONCLUSIONS: These findings provide data-driven insights into smoking-related alterations in brain functional connectivity patterns related to appetitive, relaxing, and stressful states. IMPLICATIONS: This study uses a data-driven approach to demonstrate that smokers and nonsmokers show differential patterns of functional connectivity during guided imagery related to personalized favorite-food, stress, and neutral-relaxing cues, in brain regions implicated in attention, reward-related, emotional, and motivational processes. For smokers, these differences in connectivity may impact appetite, stress, and relaxation, and may interfere with smoking cessation.

Blunted striatal responses to favorite-food cues in smokers.

BACKGROUND: Although tobacco-smoking is associated with relatively leaner body mass and smoking cessation with weight gain, the brain mechanisms underlying these relationships are not well understood. Smokers compared to non-smokers have shown diminished neural responses to non-tobacco rewarding stimuli (e.g., monetary rewards), but brain responses to favorite-food cues have not been investigated relative to smoking status. We hypothesized that smokers would exhibit diminished neural responses compared to non-smokers in response to favorite-food cues in motivation-reward and emotion-regulating regions of the brain. METHODS: Twenty-three smokers and 23 non-smokers matched based on body mass index (BMI), age, and gender listened to personalized favorite-food cue, stress, and neutral-relaxing audiotapes during fMRI. RESULTS: During favorite-food cue exposure, smokers versus non-smokers exhibited diminished activations in the caudate, putamen, insula, and thalamus. Neural responses during stress and neutral-relaxing conditions were similar across groups. Subjective food-craving ratings were similar across groups. CONCLUSIONS: The relatively diminished neural responses to favorite-food cues in smokers may contribute to lower BMI.

Body mass index, metabolic factors, and striatal activation during stressful and neutral-relaxing states: an FMRI study.

Stress is associated with alterations in neural motivational-reward pathways in the ventral striatum (VS), hormonal/metabolic changes, and weight increases. The relationship between these different factors is not well understood. We hypothesized that body mass index (BMI) status and hormonal/metabolic factors would be associated with VS activation. We used functional magnetic resonance imaging (fMRI) to compare brain responses of overweight and obese (OW/OB: BMI ≥ 25 kg/m(2): N=27) individuals with normal weight (NW: BMI<18.5-24.9 kg/m(2): N=21) individuals during exposure to personalized stress, alcohol cue, and neutral-relaxing situations using a validated, autobiographical, script-driven, guided-imagery paradigm. Metabolic factors, including fasting plasma glucose (FPG), insulin, and leptin, were examined for their association with VS activation. Consistent with previous studies, stress and alcohol cue exposure each increased activity in cortico-limbic regions. Compared with NW individuals, OW/OB individuals showed greater VS activation in the neutral-relaxing and stress conditions. FPG was correlated with VS activation. Significant associations between VS activation and metabolic factors during stress and relaxation suggest the involvement of metabolic factors in striatal dysfunction in OW/OB individuals. This relationship may contribute to non-homeostatic feeding in obesity.