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Obesity-programmed mice are rescued by early genetic intervention.

ABSTRACT: Obesity is a chronic metabolic disorder affecting half a billion people worldwide. Major difficulties in managing obesity are the cessation of continued weight loss in patients after an initial period of responsiveness and rebound to pretreatment weight. It is conceivable that chronic weight gain unrelated to physiological needs induces an allostatic regulatory state that defends a supranormal adipose mass despite its maladaptive consequences. To challenge this hypothesis, we generated a reversible genetic mouse model of early-onset hyperphagia and severe obesity by selectively blocking the expression of the proopiomelanocortin gene (Pomc) in hypothalamic neurons. Eutopic reactivation of central POMC transmission at different stages of overweight progression normalized or greatly reduced food intake in these obesity-programmed mice. Hypothalamic Pomc rescue also attenuated comorbidities such as hyperglycemia, hyperinsulinemia, and hepatic steatosis and normalized locomotor activity. However, effectiveness of treatment to normalize body weight and adiposity declined progressively as the level of obesity at the time of Pomc induction increased. Thus, our study using a novel reversible monogenic obesity model reveals the critical importance of early intervention for the prevention of subsequent allostatic overload that auto-perpetuates obesity.

SUBMITTER: Bumaschny VF

PROVIDER: S-EPMC3484438 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Obesity-programmed mice are rescued by early genetic intervention.

Bumaschny Viviana F VF Yamashita Miho M Casas-Cordero Rodrigo R Otero-Corchón Verónica V de Souza Flávio S J FS Rubinstein Marcelo M Low Malcolm J MJ

The Journal of clinical investigation 20121024 11

Obesity is a chronic metabolic disorder affecting half a billion people worldwide. Major difficulties in managing obesity are the cessation of continued weight loss in patients after an initial period of responsiveness and rebound to pretreatment weight. It is conceivable that chronic weight gain unrelated to physiological needs induces an allostatic regulatory state that defends a supranormal adipose mass despite its maladaptive consequences. To challenge this hypothesis, we generated a reversi ...[more]

PMID: 23093774

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Project description:BackgroundEffective, resource-efficient treatment is urgently needed to address the high rates of pediatric and adolescent obesity. This need has been accelerated by the COVID-19 pandemic. The use of a mobile health tool as an early intervention before a clinic-based multidisciplinary weight management program could be an effective treatment strategy that is appropriate during a pandemic.ObjectiveThis study aims to assess the effectiveness of and adolescent engagement with a mobile app-based lifestyle intervention program as an early intervention before enrollment in a clinic-based multidisciplinary weight management program.MethodsThis prospective single-cohort study involved adolescents, aged 10-16 years, who were overweight and obese (defined as BMI percentile above the 85th percentile). Participants used the mobile Kurbo app as an early intervention before enrolling in a clinic-based multidisciplinary weight management program. Kurbo's health coaches provided weekly individual coaching informed by a model of supportive accountability via video chat, and participants self-monitored their health behavior. The implementation of Kurbo as an early intervention was evaluated using the reach, effectiveness, adoption, implementation, and maintenance framework by reach (number who consented to participate out of all patients approached), implementation (Kurbo engagement and evaluation), and effectiveness as measured by the primary outcome of the BMI z-score at 3 months. Secondary outcome measures included changes in body fat percentage, nutrition and physical activity levels, and quality of life at 3 months. Maintenance was defined as the outcome measures at 6-month follow-up.ResultsOf the 73 adolescents who were approached for enrollment, 40 (55%) of adolescents were recruited. The mean age was 13.8 (SD 1.7) years, and the mean BMI z-score was 2.07 (SD 0.30). In the multiethnic Asian sample, 83% (33/40) of the participants had household incomes below the national median. Kurbo engagement was high, with 83% (33/40) of participants completing at least 7 coaching sessions. In total, 78% (18/23) of participants rated the app as good to excellent and 70% (16/23) stated that they would recommend it to others. There were no statistically significant changes in BMI z-scores at 3 months (P=.19) or 6 months (P=.27). Participants showed statistically significant improvements in measured body fat percentage, self-reported quality of life, and self-reported caloric intake from the 3-day food diaries at 3 and 6 months.ConclusionsThe use of Kurbo before enrollment in an outpatient multidisciplinary clinical care intervention is a feasible strategy to expand the reach of adolescent obesity management services to a low-income and racially diverse population. Although there was no significant change in BMI z-scores, the use of Kurbo as an early intervention could help to improve quality of life and reduce body fat percentage and total caloric intake.

Project description:BackgroundAlthough paternal involvement in the perinatal period is associated with benefits for maternal-child health and reduced obesity risk, fathers are seldom included in perinatal or obesity prevention efforts. Engaging community leaders and fathers as stakeholders in intervention development is a critical step in designing a father-inclusive intervention that is efficacious and responsive to their needs.MethodsWe conducted a structured engagement study, including community stakeholder engagement and qualitative interviews with new fathers, to inform the development of a prospective randomized controlled trial that includes mothers and fathers as equal partners in infant obesity prevention. We interpreted stakeholder feedback through the Consolidated Framework for Implementation Research (CFIR) framework.ResultsBetween September 2019 and April 2020, we held a Community Engagement meeting, formed a Community Advisory Board, and conducted 16 qualitative interviews with new fathers. Stakeholder engagement revealed insights across CFIR domains including intervention characteristics (relative advantage, complexity, design quality & packaging), outer setting factors (cosmopolitanism and culture), individual characteristics (including self-efficacy, state of change, identification with the organization) and process (engagement and adaptation). Stakeholders discussed the diverse challenges and rewards of fatherhood, as well as the intrinsic paternal motivation to be a loving, supportive father and partner. Both community leaders and fathers emphasized the importance of tailoring program delivery and content to meet specific parental needs, including a focus on the social-emotional needs of new parents.ConclusionsA structured process of multidimensional stakeholder engagement was successful in improving the design of a father-inclusive perinatal obesity prevention interventions. Father engagement was instrumental in both reinforcing community ties and increasing our understanding of fathers' needs, resulting in improvements to program values, delivery strategies, personnel, and content. This study provides a practical approach for investigators looking to involve key stakeholders in the pre-implementation phase of intervention development.Trial registrationClinicalTrials.gov, NCT04477577 . Registered 20 July 2020.

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Obesity-programmed mice are rescued by early genetic intervention.

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Obesity-programmed mice are rescued by early genetic intervention.

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