Reprogramming energy homeostasis in children with overweight through cognitive training and social interaction. A study protocol to estimate leptin sensitivity

Valentina Russo¹Deny Menghini^1*Marco Mainardi^2,3Danilo Fintini⁴Alessia Aureli⁴Nicoletta Gianni⁵Lucilla Ravà⁶Maria Alessia Rea⁵Gabriele Scozia¹Chiara Spiezia⁷Gaia Scabia³Giulia Furini³Stefano Vicari^1,8Stefano Cianfarani^4,9Margherita Maffei³Melania Manco^5*

• ¹Child and Adolescent Neuropsychiatry Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
• ²Department of Biomedical Sciences, University of Padua, Padua, Italy
• ³Institute of Clinical Physiology, National Research Council, Pisa, Italy
• ⁴Endocrinology and Diabetes Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
• ⁵Research Unit for Preventive and Predictive Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
• ⁶Clinical Epidemiology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
• ⁷Research Unit of Food Science and Human Nutrition, Department of Science and Technology for Sustainable Development and One Health, Campus Bio-Medico University, Rome, Italy
• ⁸Department of Life Science and Public Health, Catholic University of the Sacred Heart, Rome, Italy
• ⁹Department of Women's and Children's Health, Karolinska Institute and University Hospital, Stockholm, Sweden

Leptin is a hormone secreted by adipocytes in proportion to the size of adipose tissue. By acting on its receptor, LepRb, primarily expressed in the hypothalamus, leptin promotes a negative energy balance by strongly suppressing appetite and stimulating energy expenditure. The majority of patients with obesity exhibit elevated leptin production, indicating that leptin becomes ineffective in regulating energy balance in this context. In the growing child, leptin modulates synaptic plasticity and thus leptin resistance may exert a key role in neurodevelopment. So far, studies in humans have investigated leptin secretion but not leptin resistance. We designed a research protocol (RESILIENT project) to study leptin sensitivity in vivo and ex vivo in growing children (6 to 11 years of age), and its association with neurodevelopmental features. The project will investigate the additive effects of Cognitive Training (CT) and Social Training (ST) on leptin sensitivity, compared to stand-alone Intensive Health Behaviour Treatment (IHBT) in children with obesity or overweight. In vivo investigation of leptin sensitivity may be particularly important for providing evidence of the metabolic and cognitive effects necessary for developing novel anti-obesity treatments.