Depressive symptoms attenuate the association between FGF21 response and sucrose intake in older adults

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BACKGROUND: Depressive symptoms in late life are often accompanied by altered appetite and dietary behavior, yet the biological mechanisms linking metabolic signals to eating behavior remain poorly understood. Fibroblast growth factor 21 (FGF21) is a carbohydrate responsive hepatokine that suppresses sweet preference via central pathways. We examined whether depressive symptoms modify the association between FGF21 and sucrose intake in Japanese older adults, focusing on post-glucose FGF21 response. METHODS: This cross-sectional study from the Bunkyo Health Study in Tokyo, Japan, included 1433 adults aged 65-84 years. Serum FGF21 levels were measured during a 75-g oral glucose tolerance test, and post-glucose responsiveness was assessed using the incremental area under the curve (iAUC). Geriatric depressive symptoms (GDS) were defined as a Geriatric Depression Scale (GDS-15) score ≥ 5. Sucrose intake was compared using two-way Analysis of Covariance (ANCOVA) across groups stratified by GDS and FGF21 responsiveness. RESULTS: GDS were present in 303 participants (21.1%). The association between FGF21 response and sucrose intake differed significantly by GDS status (interaction p = 0.045): among those without GDS, higher FGF21 response was associated with lower sucrose intake (2.80% vs. 3.17%; p < 0.001), whereas no association was observed in participants with GDS (3.08% vs. 3.00%; p = 0.780). CONCLUSIONS: Post-glucose FGF21 response is associated with lower habitual sucrose intake in older adults, but this association is attenuated among individuals with GDS. These observations may inform integrated endocrine and psychological approaches to mitigating nutritional imbalance in late-life depression.

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