Inulin ameliorates sarcopenic obesity: critical roles of gut microbiota and bile acid metabolism.

Abstract

The concurrent manifestation of muscle wasting and excessive adiposity, termed Sarcopenic Obesity (SO), represents a growing public health challenge. Inulin, a widely used prebiotic, has been shown to improve metabolic disorders, but its specific effects on SO and the mechanisms governing the gut-liver-muscle axis remain underexplored. This study evaluated the therapeutic potential of inulin in db/db mice exhibiting SO features. Our data indicate that inulin supplementation effectively curbed weight gain and fat deposition while preserving lean mass. Crucially, it ameliorated systemic hyperglycemia and dyslipidemia. In the liver, inulin attenuated steatosis by potentiating the AMPK/PPARα oxidative pathway; in skeletal muscle, it reversed atrophy by enhancing myogenic factors (MyoD and MyHC I) and suppressing atrophic ligases (Atrogin-1 and MuRF1). Mechanistically, inulin restored intestinal barrier integrity, thereby reducing serum lipopolysaccharide (LPS) and proinflammatory cytokine levels. Metagenomic sequencing and targeted metabolomics revealed that inulin restructured the gut microbiota composition, characterized by an enrichment of Ligilactobacillus, Prevotella and Bifidobacterium, and modulated the bile acid (BA) profile. Crucially, protein quantification confirmed that inulin significantly upregulated the expression of core bile acid receptors (FXR and TGR5) in both colonic and hepatic tissues. These findings demonstrate that inulin ameliorates SO through an integrated mechanism involving gut microbiota remodeling, BA-FXR/TGR5 receptor activation, and intestinal barrier reinforcement to harmonize the gut-liver-muscle axis, highlighting its potential as a functional food ingredient for managing SO.