A galactoglucomannan from Termitomyces intermedius: Structural characterization, anti-obesity and anti-inflammatory activities

Termitomyces mushrooms exhibit a wide range of beneficial properties, yet detailed structural characterization and exploration of their structure-activity relationships, particularly in the anti-obesity contexts, remain limited. A novel galactoglucomannan (TIP-1-1) was isolated from Termitomyces intermedius. Structural analysis showed TIP-1-1 is a 2.7 kDa polysaccharide mainly composed of glucose, galactose and mannose (mass ratio: 75.7: 10.7: 13.6). The backbone contained linear 1,6-linked β-Glcp, 1,3-linked β-Glcp, 1,6-linked α-Galp, and 1,3,6-linked α-Manp contained a branched structure that substituted primarily with 1,3,6-linked α-Manp and 1,3-linked β-Glcp residues. Functionally, TIP-1-1 mitigated HFD-induced obesity in mice by reducing body weight, fat mass, and improving glucose homeostasis and lipid profiles, with effects comparable to GLP-1. It suppressed pro-inflammatory cytokines such as NO, TNF-α, IL-6, IL-1β, leptin and restored adiponectin and IL-10 levels both in vivo and in vitro, suggesting anti-inflammatory mechanisms underlying its anti-obesity effects. In lipid metabolism studies, TIP-1-1 inhibited adipocyte lipogenesis by activating AMPK, suppressing the expression of ACC and FASN, and reducing triglyceride accumulation. Mechanistically, AMPK siRNA knockdown abolished these effects, confirming its central role in TIP-1-1-mediated suppression of de novo fatty acid synthesis. These findings established TIP-1-1 as a dual-acting anti-obesity agent with therapeutic potential via anti-inflammatory and AMPK/ACC/FASN lipogenic inhibition.