Modulating endogenous PYY expression offers a theoretical basis for individualized obesity management strategies

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Frontiers in Medicine Published June 4, 2026 Medically reviewed June 4, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider modulating endogenous PYY expression as a theoretical basis for individualized obesity management strategies.

This narrative review explores the potential of modulating endogenous PYY expression as a strategy for managing overweight and obesity. The authors synthesize information regarding dietary interventions, bariatric surgery, exercise therapy, and physical therapy as methods to achieve this modulation. The scope of the review is conceptual rather than empirical, as it does not report specific outcomes or safety data. No specific population, sample size, or setting is defined within the source text. The authors do not report primary or secondary outcomes, adverse events, or tolerability profiles. Consequently, the review serves primarily to establish a theoretical basis and conceptual framework. This framework aims to guide the development of individualized obesity management strategies. The lack of reported data limits the ability to draw definitive clinical conclusions regarding efficacy or safety. Practitioners should interpret these findings as a conceptual guide rather than evidence of proven benefit.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

Endogenous peptide YY (PYY) plays a pivotal role in the regulation of appetite and body weight, and the upregulation of its expression provides a novel strategy for obesity intervention. This review systematically elaborates on the physiological functions of PYY, its secretory mechanisms, and the potential for promoting endogenous expression through multiple approaches. PYY is primarily secreted by intestinal L-cell. By activating NPY2R in the hypothalamic arcuate nucleus, it modulates the POMC/CART-NPY/AgRP neuronal circuitry and delays gastrointestinal motility, thereby reducing appetite. The synthesis and secretion of PYY are precisely regulated by multiple mechanisms, including nutrient sensors and nutrient transporters on L-cell. Dietary interventions, bariatric surgery, exercise therapy, and physical therapy can all upregulate Endogenous PYY levels by acting on L-cell or related signaling pathways, ultimately yielding benefits of appetite suppression and metabolic improvement. These intervention strategies mimic physiological pathways more closely, carry a lower risk of side effects, and may produce synergistic effects with conventional pharmacological agents. This article aims to synthesize current evidence, providing a theoretical basis and conceptual framework for developing individualized obesity management strategies based on Endogenous PYY modulation.