Krill oil alleviates type 2 diabetes mellitus-induced sarcopenia in mice

Krill oil (KO), a source of EPA, DHA, phospholipids, and astaxanthin, has emerged as a promising functional ingredient to maintain skeletal muscle health. However, its protective role against type 2 diabetes mellitus (T2DM)-induced sarcopenia has remained poorly characterized. Hence, the present study aimed to investigate the protective effects and underlying mechanisms of KO against sarcopenia in both a T2DM mouse model induced by the combination of streptozotocin and high-fat, high-sucrose diet, and a C2C12 myotube atrophy model induced by high glucose (HG), advanced glycation end products (AGEs), and lipopolysaccharide (LPS). Incorporation of 1.5% KO (w/w) in the diet of mice with T2DM for 24 weeks significantly enhanced insulin sensitivity, lowered blood glucose levels, and decreased serum and muscle AGEs levels. Additionally, dietary KO markedly ameliorated intestinal barrier dysfunction in mice with T2DM, as evidenced by the improvement of intestinal pathological injuries, the decrease of serum and muscle LPS levels, and the restoration of the expression of tight junction proteins. Dietary KO also significantly mitigated skeletal muscle mass and strength loss in mice with T2DM, and alleviated HG/AGEs/LPS-induced C2C12 myotube atrophy. Moreover, dietary KO effectively reduced the overproduction of pro-inflammatory cytokines and ROS accumulation in the skeletal muscle of mice with T2DM and in HG/AGEs/LPS-stimulated C2C12 myotubes. Furthermore, dietary KO alleviated T2DM-induced skeletal muscle protein turnover impairment both in vivo and in vitro, as demonstrated by increased de novo protein synthesis via activating the PI3K/Akt/mTOR signaling pathway, and inhibited excessive protein degradation through inactivating the FoxO3a- and NF-κB-mediated up-regulation of MAFbx and MuRF1. Overall, our findings suggested that KO might have therapeutic potential against T2DM-induced sarcopenia.