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Updated: Apr 10, 2026

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
Genetic risk modifies the effect of exogenous nucleotides on insulin resistance in older adults: insights from
Ruisheng Fu1, Shuyue Wang1, Yuxiao Wu1
1Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, China. xumeihong@bjmu.edu.cn.
Abstract:
Nucleotides-fundamental cellular building blocks-are an underappreciated dietary component, especially in aging when metabolic resilience wanes. Whether genetic background determines who benefits from NTs has been unknown. Insulin resistance (IR) underlies age-related metabolic disorders, yet responses to nutritional interventions are heterogeneous. In this secondary analysis of the TALENTs randomized controlled trial (121 adults aged 60-70 years; 19-week intervention; NCT05243108), we tested whether genetic background-quantified by a fasting-glucose polygenic risk score (FBG-PRS)-modifies the effect of exogenous nucleotides (NTs) on IR. A significant PRS × intervention interaction was observed with changes in HOMA-IR (p = 0.0115). Participants with high FBG-PRS exhibited improvements with NTs, including reduced HOMA-IR and visceral adiposity and increased limb muscle mass, whereas low FBG-PRS participants showed minimal benefit. Multi-omics supported a coherent mechanism: transcriptomics identified 39 differentially expressed genes with PPP4R2 most strongly downregulated (log 2FC = -2.00; padj = 2.81 × 10-13), and metabolomics revealed decreased cyclic AMP with enrichment of energy-metabolism pathways. These findings indicate that NTs improve insulin sensitivity primarily in genetically susceptible older adults and suggest NTs as a candidate precision-nutrition strategy for improving insulin sensitivity in aging.
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