Barley β-glucan reduced fatty liver and improved blood fats in mice fed a Western-style diet

Objective

To determine whether highland barley β-glucan (BG) mitigates Western-diet (WD)–induced nonalcoholic fatty liver disease (NAFLD) in mice, and to delineate hepatic lipidomic and gene expression changes underlying any benefit. 

Methods 

• Male C57BL/6 mice (n=40) were randomized (8/group) for 16 weeks to: normal diet (ND); WD (42% kcal fat) plus 4.2% sugar water (18.9 g/L sucrose, 23.1 g/L fructose); WD+BG 100 mg/kg (LBG); WD+BG 300 mg/kg (HBG); or WD+orlistat 20 mg/kg (positive control). 
• BG (from Tibetan hull-less barley) and orlistat were dosed daily; ND/WD animals received saline. 
• Outcomes: body/organ weights; serum lipids (TC, TG, HDL-c, LDL-c) and transaminases (ALT/AST); hepatic TC/TG/FFA; liver histology (H&E, Oil Red O) and NAFLD Activity Score (NAS).
• Untargeted hepatic lipidomics was performed in ND, WD, and HBG subsets (n=6/group) to identify differential lipids and pathway enrichment; hepatic mRNA of lipid and cholesterol-metabolism genes was quantified (RT-qPCR). 

Results 

• Weight/adiposity & liver: WD increased body weight gain, epididymal fat, and liver index vs ND; BG (both doses) reduced weight gain and epididymal fat vs WD, with greater effects at 300 mg/kg; the liver index was significantly reduced by HBG. 
• Histology showed WD-induced macrovesicular steatosis and elevated NAS, both attenuated by HBG. Hepatic TC, TG, and FFA were all lower with HBG vs WD. 
• Serum biochemistry: WD raised TC, TG, LDL-c and ALT/AST vs ND; BG decreased TC, TG, LDL-c and transaminases, and HBG increased HDL-c toward ND levels. 
• Hepatic lipidomics: WD vs ND yielded 534 differential lipid species; HBG vs WD yielded 124 species with partial reversion toward ND in PCA/OPLS-DA. Thirteen lipids met stringent biomarker criteria; WD increased many of these, HBG reversed them. 
• Pathway analysis highlighted correction of glycerophospholipid (GP) and glycerolipid (GL) metabolism, and improvements in sphingolipids (e.g., ceramides). Correlative analyses linked HBG-shifted lipids with improvements in hepatic/serum lipids and enzymes. 
• Gene expression (liver): WD upregulated SREBP-1c and FAS (lipogenesis); HBG downregulated both and upregulated AMPKα, PPARα, CPT1α (fatty-acid oxidation) and CYP8B1, CYP27A1 (bile-acid–mediated cholesterol catabolism).

Interpretation 

Daily high-dose barley β-glucan (300 mg/kg) significantly ameliorated WD-induced steatosis, normalizing serum and hepatic lipid disturbances and liver injury markers, with multi-omic evidence for reduced de novo lipogenesis, enhanced β-oxidation, and increased cholesterol disposal via bile acids. Lipidomic restoration in GP/GL/SL pathways (e.g., PCs/PEs, TGs/DGs, ceramides/HexCer) which correlates with the mRNA profile (decreased SREBP-1c/FAS; increased AMPK-α/PPAR-α/CPT1-α; increased CYP8B1/CYP27A1). 

Mechanisms & pathways discussed 

Proposed drivers include: (1) suppression of hepatic lipogenesis (reduced SREBP-1c and FAS); (2) activation of fatty-acid oxidation (increased AMPKα and CPT1α/PPARα); (3) enhanced bile-acid synthesis (elevated CYP8B1/CYP27A1) lowering hepatic CE/TC; and (4) lipotoxic sphingolipid remodeling (lower ceramide/HexCer species). Lipid-pathway enrichment pinpointed glycerophospholipid and glycerolipid metabolism as key nodes corrected by BG. 

Dosages & adverse reactions 

BG 100 or 300 mg/kg/day (oral) for 16 weeks; comparator orlistat 20 mg/kg/day; WD contained 42% fat plus sucrose/fructose sugar water. No reported adverse events. 

Quality of study 

Strengths: randomized group assignment; multi-tiered readouts (biochemistry, histology, lipidomics, transcription); orthogonal separation/validation in OPLS-DA; pathway and correlation analyses; positive control arm. 

Limitations: mouse model (male only); reliance on mRNA (no protein/activity assays); no direct bile-acid quantification or insulin sensitivity testing; WD model includes fructose/sucrose water which may differentially affect pathways. 

Implications

In WD-induced NAFLD, barley β-glucan (notably 300 mg/kg) safely improves hepatic fat accumulation, serum/hepatic lipids, and liver injury markers, with coherent remodeling of lipid pathways and gene networks tied to lipogenesis, β-oxidation, sphingolipids, and bile-acid–mediated cholesterol clearance. Findings support BG as a candidate dietary adjunct for metabolic-liver risk but require more study in human trials, dose translation, and mechanistic confirmation.