A yeast fiber (β-glucan) lowered blood sugar and reduced liver fat in diabetic mice by blocking gut absorption and resetting liver metabolism.

Objective
To test whether orally administered, purified Baker’s yeast β-(1→3)-glucan (BYG) improves glucose and lipid homeostasis in the liver of ob/ob (obese/diabetic) mice, and to delineate intestinal and hepatic mechanisms using protein, gene-expression, and functional readouts. 

Methods

• Male ob/ob mice (11–12 weeks) were randomized (n=7/group) to BYG 25 mg/kg/day orally for 4–5 weeks vs water. 
• Outcomes included: 
  • Fasting glucose, glucose tolerance test (OGTT) on day 15 (Area under curve, AUC, calculated), pyruvate tolerance test (gluconeogenesis)
  • Liver histology (H&E, Oil Red O) and Western blots (p-AKT, p-AMPK, p-ACC, FASN
  • Liver gene expression (qRT-PCR of lipogenic/gluconeogenic genes) and RNA-seq
  • Intestinal glucose transporters & lipid-handling proteins (WB and mRNA on SGLT1, GLUT2) 
• Male Sprague−Dawley (SD) rats (7 weeks old) on normal diet. After starvation for 6 hours, the rats were given BYG solution (50 mg/kg, BYG group, n = 5) or water (control group, n = 5) orally. 30 minutes later, 1.5 mL of lard was given via gavage. 
  • Blood samples were collected before the gavage (0 h) and at 1 and 3 h after the gavage of lard, and serum triglycerides (TG) were measured
• In vitro bile acid binding (cholic acid) and emulsification tests assessed intestinal mechanisms.

Results

• Glycemia: BYG lowered fasting glucose and OGTT AUC vs control, gluconeogenesis was blunted on the pyruvate test. 
• Hepatic signaling proteins and histology: increased p-AKT and p-AMPK levels, decreased p-ACC, and reduced hepatic lipid droplets on Oil Red O. 
• Hepatic transcriptional program: RNA-seq/qPCR showed down-regulation of genes for gluconeogenesis (G6pc, Got1), fatty-acid synthesis/elongation (Acly, Acaca/Acc, Fasn, Elovl6, Acot3), glycerolipid synthesis (Gpam, Lpin1/2), and cholesterol/bile-acid pathways (Hmgcr, Fdps, Msmo1, Sc5d, Cyp7a1, Cyp8b1, Aqp8). 
• Intestinal mechanisms: Jejunal SGLT1 and GLUT2 protein levels fell with BYG; intestinal p-AMPK, p-ACC, FASN and lipogenic gene mRNAs decreased. 
• BYG reduced post-prandial TG in the rat fat-tolerance test, consistent with lower lipid absorption. 
• In vitro, BYG bound cholic acid and weakened emulsification effect of cholic acid (supporting reduced fat emulsification/absorption).

Interpretation
Oral BYG improved hyperglycemia and hepatic steatosis in ob/ob mice via a two-compartment mechanism: (1) Intestine: reduced glucose (SGLT1/GLUT2) and lipid uptake (bile-acid binding, impaired emulsification) and dampened enterocyte lipogenesis, (2) Liver: activation of AKT/AMPK with broad suppression of gluconeogenic, lipogenic, and cholesterogenic gene networks, lowering hepatic lipid burden and glucose output. Direct hepatocyte actions were not evident, implicating gut-mediated pathways.

Mechanisms and pathways

• Hepatic: increased AKT/AMPK, decreased SREBP-1c axis and downstream ACC/FASN, decreased G6pc/Got1 (gluconeogenesis), HMGCR/FDPS (cholesterol) and CYP7A1/CYP8B1 (bile acids). 
• Intestinal: decreased SGLT1/GLUT2, decreased p-AMPK, p-ACC, FASN, reduced bile acid binding resulting in reduced lipid emulsification/absorption; net effect is reduced substrate influx to liver. 

Dosages and adverse reactions

• Mice: BYG 25 mg/kg/day PO for 4–5 weeks.
• Rats (fat test): BYG 50 mg/kg single dose.

Quality of study 
Strengths: integrated physiology–biochemistry–omics package (OGTT/PTT, histology, WB, qPCR, RNA-seq), intestinal mechanism assays, dose defined, and cross-species fat-tolerance test. 

Limitations: preclinical; modest group sizes (e.g., n=7 mice, RNA-seq n=2/group, qPCR n=3, WB n=4); single dose/duration. 

Implications
For metabolic disease biology, insoluble yeast β-glucan can improve hepatic glucose–lipid balance predominantly via intestinal uptake suppression plus hepatic AKT/AMPK activation. This suggests a mechanistic profile distinct from viscous cereal β-glucans. Clinical applicability awaits human trials to define dose, formulation, durability, and safety.