Fucoidan Improves Early Stage Diabetic Nephropathy via the Gut Microbiota–Mitochondria Axis in High-Fat Diet-Induced Diabetic Mice

Abstract

Diabetic nephropathy (DN) is a common microvascular complication of diabetes. Fucoidan, a polysaccharide containing fucose and sulfate group, ameliorates DN. However, the underlying mechanism has not been fully understood. This study aimed to explore the effects and mechanism of fucoidan on DN in high-fat diet-induced diabetic mice. A total of 90 C57BL/6J mice were randomly assigned to six groups (n = 15) as follows: normal control (NC), diabetes mellitus (DM), metformin (MTF), lowdose fucoidan (LFC), medium-dose fucoidan (MFC), and high-dose fucoidan (HFC). A technique based on fluorescein isothiocyanate (FITC-sinistin) elimination kinetics measured percutaneously was applied to determine the glomerular filtration rate (GFR). After 24 weeks, the mice were sacrificed and an early stage DN model was confirmed by GFR hyperfiltration, elevated urinary creatinine, normal urinary albumin, tubulointerstitial fibrosis, and glomerular hypertrophy. Fucoidan significantly improved the GFR hyperfiltration and renal fibrosis. An enriched SCFAs-producing bacteria and increased acetic concentration in cecum contents were found in fucoidan groups, as well as increased renal ATP levels and improved mitochondrial dysfunction. The renal inflammation and fibrosis were ameliorated through inhibiting the MAPKs pathway. In conclusion, fucoidan improved early stage DN targeting the microbiota−mitochondria axis by ameliorating mitochondrial oxidative stress and inhibiting the MAPKs pathway.