Wheat insoluble dietary fiber attenuates high-fat diet-induced lipid metabolic disorders in a gut microbiota-dependent manner: correlative evidence for microbiota-associated branched-chain amino acids and a putative AMPK-centered signaling hypothesis

Dietary fiber mediated modulation of gut microbiota represents a promising strategy for managing metabolic disorders. Wheat bran, a major by-product of global wheat production, is rich in insoluble dietary fiber. However, the host-microbe interactions through which wheat insoluble dietary fiber (WIDF) influences metabolism remain incompletely characterized. In this study, concurrent WIDF supplementation attenuated high fat diet (HFD) induced metabolic dysfunction, reducing body weight by 14% ( P  < 0.05) at week 12 and ameliorating liver steatosis and obesity. It also significantly improved blood and liver lipid profiles (serum and liver TC reduced by 29.4% and 29.9%, respectively; serum and liver TG reduced by 23.7% and 45.7%, respectively; P  < 0.05), alleviated oxidative stress by reducing MDA content and raising GSH levels, and enhanced glucose tolerance ( P  < 0.05). Multiple bacterial genera including norank_f_ Muribaculaceae, Romboutsia , and Candidatus_Saccharimonas , were correlatived with these metabolic improvements. Correlative metabolomic profiling identified microbiota-associated L-leucine and L-valine, two branched-chain amino acids (BCAAs), as candidate metabolites. In vitro HepG2 experiments suggested that L-leucine and L-valine were associated with changes in AMPK related signaling at supraphysiological concentrations and with reduced oleic acid induced lipid accumulation. Antibiotic depletion and fecal microbiota transplantation experiments supported the involvement of gut microbiota in the metabolic effects of WIDF. The observed association among WIDF related gut microbiota changes, BCAA availability, and AMPK related signaling provides a hypothesis that requires further in vivo validation. Download: Download high-res image (397KB) Download: Download full-size image