Molecular weight-dependent effects of Undaria pinnatifida fucoidan isolates on palmitate-induced inflammation and muscle atrophy in C2C12 myotubes

Abstract

Obesity is consistently linked to skeletal muscle atrophy. It is characterized by a chronic inflammatory state that produces various pro-inflammatory substances that may have negative effects on muscles, such as muscle atrophy, impaired muscle regeneration, and a reduction in muscle protein synthesis. Fucoidan, isolated from the brown alga Undaria pinnatifida, is composed of fucose, galactose, and sulfate groups, and is known to have anti-obesity, anti-tumor, and immunomodulatory properties. Recent studies have indicated that the bioactivity of fucoidans depends on their molecular weight; however, this correlation remains unclear and requires further investigation. This study aimed to evaluate and compare the effects of three different fucoidans, based on their molecular weight, on palmitate (PA)-induced muscle atrophy using C2C12 myotubes. The fucoidan types were low molecular weight fucoidan (LMWF, >= 30 kDa), medium molecular weight fucoidan (MMWF, >= 110 kDa), and high molecular weight fucoidan (HMWF, >= 200 kDa). Our results demonstrate that all fucoidans reduced lipid accumulation. Additionally, all three fucoidans reduced tumor necrosis factor-alpha (TNF-alpha) mRNA expression level in PA-induced inflammation, whereas interleukin-1beta (IL-1 beta) and IL-6 mRNA expression levels were reduced only in the HMWF-treated group. Moreover, MMWF and HMWF significantly reduced the mRNA expression levels of the muscle atrophy genes muscle RING-finger protein-1 (MuRF1) and Atrogin-1, while LMWF showed no significant effects. In conclusion, HMWF showed more promising outcomes than LMWF and MMWF, suggesting its potential as a therapeutic agent for the treatment of obesity-induced inflammation and muscle atrophy.