Hyperphagia in Syndromic and Hypothalamic Obesity: Mechanisms, Consequences, and Interventions

Hyperphagia, defined as an intense and insatiable hunger drive, contributes significantly to excessive weight gain and cardiometabolic complications in affected individuals. It is a

characteristic of certain rare syndromes, including Prader-Willi syndrome and Bardet-Biedl syndrome, and is also associated with hypothalamic obesity, which arises from damage to the hypothalamus.

The hypothalamus plays a central role in regulating both energy intake and expenditure. Disruptions in hypothalamic function can lead not only to increased hunger but also to altered energy expenditure, including the thermic effect of food. In syndromes like Bardet-Biedl syndrome, melanocortin-4 receptor (MC4R) pathway defects are thought to drive hyperphagia, alongside possible contributions from other pathways.

Assessing hyperphagia poses unique challenges, as it is often measured through self-report questionnaires completed by caregivers or, in some cases, the affected individuals. This

subjective approach can be influenced by factors unrelated to true hunger drive, such as communication ability, self-regulation of hunger response, and cultural perceptions of “normal” hunger.

This Research Topic will explore three main areas:


1. Assessment of Hyperphagia: This includes evaluating current self-report measures and exploring biomarkers as complementary tools. Reliable hyperphagia assessments are essential for understanding its role in obesity progression and for evaluating intervention effectiveness in reducing hyperphagia’s impact on daily functioning and weight gain.

2. Metabolic Consequences of Hyperphagia in Obesity: This includes exploring physiologic outcomes such as glucose metabolism and energy expenditure related to hyperphagia.

3. Treatments for Hyperphagia: Therapeutic approaches include MC4R-targeting medications, glucagon-like peptide-1 receptor agonists, and intensive behavioral interventions aimed at modulating emotional and behavioral responses to hunger, even when they do not directly reduce hyperphagia itself.

We welcome submissions on topics including, but not limited to:

• Novel Hyperphagia Assessment Methods: From clinical to preclinical studies, including self-report, biomarkers, or integrated assessment approaches.

• Associations Between Hyperphagia and Metabolic Health: Especially how physiological factors like MC4R pathway defects influence glucose and energy metabolism.

• Exploring New Pharmaceutical and Nutraceutical Treatments: Potential interventions for hyperphagia and appetite regulation.

• Hormones and Biomarkers in Appetite Regulation: Those affecting central/hypothalamic pathways that control hunger and appetite control

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Hyperphagia, Syndromic Obesity, Hypothalamic Obesity, Prader-Willi Syndrome, Bardet-Biedl Syndrome, Melanocortin-4 Receptor (MC4R) Pathway, Energy Expenditure, Glucose Metabolism, Appetite Regulation, Therapeutic Interventions

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.