Circadian dysregulation of leptin and its role in skin inflammation and obesity: an integrative perspective

Abstract Purpose Leptin is an adipokine that regulates energy balance and is commonly linked to obesity. It exhibits a circadian rhythm that can be disrupted by variations in eating times and sleep disorders. This brief review explored how leptin can modulate appetite and tissue repair; and assessed whether dysregulated serum levels may activate pro-inflammatory pathways contributing to inflammatory dermatoses, particularly in the context of obesity. Methods Current evidence on the interconnection between leptin rhythmicity, obesity, sleep disruption, meal timing, oxidative stress, and inflammatory dermatoses was reviewed and synthesized, with an emphasis on studies relevant to the proposed circadian, metabolic and cutaneous axis. Results Available evidence indicated that irregular or late meal timing can alter leptin rhythmicity, while sleep disruption is associated with changes in leptin secretion and inflammatory mediators. In obesity, persistent hyperleptinemia may coexist with central leptin resistance and preserved peripheral pro-inflammatory signaling. Experimental and clinical findings support associations among leptin dysregulation, oxidative stress, reduced antioxidant capacity, and inflammatory pathways relevant to dermatoses related to obesity, particularly psoriasis. However, direct evidence establishing a causal relationship between circadian leptin dysregulation and skin inflammation remains limited. Conclusions Circadian leptin misalignment may represent a plausible upstream pathway linking altered meal timing, sleep disruption, leptin resistance, oxidative stress, and immune activation to obesity-associated inflammatory dermatoses. Chronobiological interventions, particularly time-restricted feeding combined with adequate sleep, warrant further investigation for their potential to improve leptin regulation and attenuate skin inflammation. Much of the current evidence remains associative, and further mechanistic and interventional studies are needed to test this hypothesis.