Improved glucose tolerance in insulin-resistant rats after pea hull feeding is associated with changes in lipid metabolism-targeted transcriptome

Understanding of the mechanisms by which pulse grain fractions elicit beneficial effects on glucose tolerance is incomplete. An untargeted metabolomic analysis of serum from insulin-resistant rats was carried out to identify potential metabolic pathways affected by feeding rats the hull fraction of dried peas for 4 weeks. From this, we hypothesized that transcription of hepatic genes involved in lipid metabolism would be altered. cDNA was prepared from total RNA extracted from livers of rats fed a high-fat diet (HFD) or HFD + pea hulls (PH) diet. The liver lipid transcriptome of each cDNA sample was characterized using a PCR-based array of 84 genes. The activity of peroxisome-proliferator-activated receptor alpha (PPAR-alpha) was measured in hepatocyte nuclei. The predominant findings of the metabolomic analysis revealed a significant increase in the intermediaries of beta-oxidation: C16-OH and C16:1 acylcarnitines (>50%, p < 0.05) and 3-hydroxybutyrate (100%, p < 0.05) in the PH group compared with the HFD group. mRNA of hadha, a gene involved in beta-oxidation, was significantly reduced by 53% (p < 0.005) in the PH group compared with the HFD group, but no differences in PPAR-alpha activity were detected. 3-Hydroxybutyrate concentrations were associated with insulin sensitivity and reduced demand for insulin. The results indicate that feeding PH alters lipid metabolism in liver, which may contribute to improved glucose tolerance in insulin-resistant rats.