Journal of advanced research · 2025
Integrated multi-omics unravels solanesol's multi-organ protection mechanisms against insulin resistance in type 2 diabetic mice.
СтатьяПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhang Wenji, Cheng Wenli, Fu Jiaqi, Zeng Ruidong, Wang Zhangying, Zhou Jingbo, Chen Yibo, Zhang Wenjuan
Аннотация
INTRODUCTION: Integrated multi-omics analysis has revolutionized the investigation of plant-derived compounds for type 2 diabetes mellitus (T2DM). Solanesol, a bioactive constituent from Solanaceae plants, exhibits high oral bioavailability and translational potential for multi-target therapeutics.
OBJECTIVES: This study aimed to elucidate the multi-target mechanisms and multi-organ protective effects of solanesol in T2DM management through integrated multi-omics approaches, to bridge the gap between phytochemical discovery and clinical translation.
METHODS: In Leprdb/db murine models (8-13 weeks), solanesol (1-15 mg/kg/day, i.g.) was compared with metformin (200 mg/kg/day). Serum biochemical parameters were quantified using ELISA/colorimetric assays. Quantitative pathology analysis was performed on H&E/PAS/Masson-stained sections for assessment of hepatic steatosis and glycogenesis. Mitochondrial respiratory chain complexes (I-V) expression and activities were validated by qRT-PCR and ELISA assay, respectively. Multi-omics profiling included gut microbiota sequencing (16S rRNA), fecal metabolomics/lipidomics (UHPLC-Q LC-MS/MS), and hepatic transcriptome/proteome analysis (RNA-seq, 4-Dimensional Label-Free Quantification (4D-LFQ)). Long-/medium-/short-chain fatty acids were detected by GC-MS.
RESULTS: Solanesol improved glucose tolerance, insulin sensitivity, and reduced serum lipids, hepatic gluconeogenesis, uric acid, white adipose mass, pancreatic/hepatic inflammation, and renal fibrosis. Mechanistically, solanesol: 1) enriched beneficial gut microbiota (Alistipes, Anaerotruncus, and Parasutterella) and increased levels of long-chain unsaturated fatty acids; 2) rebalanced the dysfunctional mitochondrial oxidative phosphorylation microenvironment by modulating the expression and the activities of respiratory chain Complexes I-V; 3) modulated hepatic lipid metabolism by inhibiting de novo lipogenesis via the Acly-Acaca-Fasn pathway, promoting cholesterol efflux and fatty acid oxidation through Abca1/Fabp5, and attenuating inflammation via Lpl-PPARδ downregulation.
CONCLUSION: Solanesol demonstrates multi-organ protective effects through gut microbiota-metabolite crosstalk and hepatic lipid/redox homeostasis regulation. Its multi-target efficacy and oral bioavailability position it as a novel, clinically translatable candidate for T2DM management.
OBJECTIVES: This study aimed to elucidate the multi-target mechanisms and multi-organ protective effects of solanesol in T2DM management through integrated multi-omics approaches, to bridge the gap between phytochemical discovery and clinical translation.
METHODS: In Leprdb/db murine models (8-13 weeks), solanesol (1-15 mg/kg/day, i.g.) was compared with metformin (200 mg/kg/day). Serum biochemical parameters were quantified using ELISA/colorimetric assays. Quantitative pathology analysis was performed on H&E/PAS/Masson-stained sections for assessment of hepatic steatosis and glycogenesis. Mitochondrial respiratory chain complexes (I-V) expression and activities were validated by qRT-PCR and ELISA assay, respectively. Multi-omics profiling included gut microbiota sequencing (16S rRNA), fecal metabolomics/lipidomics (UHPLC-Q LC-MS/MS), and hepatic transcriptome/proteome analysis (RNA-seq, 4-Dimensional Label-Free Quantification (4D-LFQ)). Long-/medium-/short-chain fatty acids were detected by GC-MS.
RESULTS: Solanesol improved glucose tolerance, insulin sensitivity, and reduced serum lipids, hepatic gluconeogenesis, uric acid, white adipose mass, pancreatic/hepatic inflammation, and renal fibrosis. Mechanistically, solanesol: 1) enriched beneficial gut microbiota (Alistipes, Anaerotruncus, and Parasutterella) and increased levels of long-chain unsaturated fatty acids; 2) rebalanced the dysfunctional mitochondrial oxidative phosphorylation microenvironment by modulating the expression and the activities of respiratory chain Complexes I-V; 3) modulated hepatic lipid metabolism by inhibiting de novo lipogenesis via the Acly-Acaca-Fasn pathway, promoting cholesterol efflux and fatty acid oxidation through Abca1/Fabp5, and attenuating inflammation via Lpl-PPARδ downregulation.
CONCLUSION: Solanesol demonstrates multi-organ protective effects through gut microbiota-metabolite crosstalk and hepatic lipid/redox homeostasis regulation. Its multi-target efficacy and oral bioavailability position it as a novel, clinically translatable candidate for T2DM management.