Lactobacillus paragasseri SBT2055 suppressed insulin resistance and fatty liver by inhibiting oxidative stress and inflammation in high-fat diet-induced obese mice

Abstract Obesity-induced metabolic disorders, including insulin resistance and type 2 diabetes mellitus (T2DM), are significant global health issues exacerbated by high-fat diets (HFD). These conditions often lead to non-alcoholic fatty liver disease (NAFLD), characterised by hepatic lipid accumulation, inflammation, and oxidative stress, which further impair insulin signalling. Probiotics, particularly those in the Lactobacillus genus, have been shown to ameliorate metabolic disorders. This study evaluated the antidiabetic and hepatoprotective effects of Lactobacillus paragasseri SBT2055 (LG2055), a sister taxon of L. gasseri , in HFD-induced obese mice. Mice supplemented with LG2055 (1 × 10 8 or 1 × 10 10 CFU/mouse/day) exhibited significant reductions in body weight, fasting blood glucose, and homeostatic model assessment for insulin resistance (HOMA-IR) values, alongside improved glucose tolerance and hepatic glycogen storage. LG2055 supplementation modulated the expression of genes involved in hepatic gluconeogenesis and intestinal glucose uptake, effectively suppressing insulin resistance. Hepatic lipid accumulation and liver weight were significantly reduced, accompanied by downregulation of lipogenic genes and proteins, while antioxidant enzyme activities {superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), and glutathione reductase (GR)} were enhanced, reducing oxidative stress markers. LG2055 also alleviated liver inflammation by decreasing plasma lipopolysaccharide (LPS) levels and suppressing Toll-like receptor signalling, as well as reducing the expression of pro-inflammatory cytokines and fibrosis-related markers. These findings suggest that LG2055 mitigates HFD-induced metabolic disturbances by improving insulin sensitivity, reducing hepatic lipid synthesis, enhancing antioxidant defences, and attenuating inflammation. LG2055 demonstrates potential as a therapeutic probiotic for the prevention and treatment of T2DM and associated metabolic disorders.