Although vitamin B6 is contained in various foods, its deficiency is one of the most common micronutrient deficiencies worldwide. Furthermore, patients with obesity and cardiovascular disease are more likely to have suboptimal vitamin B6 status than healthy people. Therefore, we investigated the effects of dietary vitamin B6 restriction on hepatic gene expression and function in obese mice. C57BL/6J male mice were fed a low-fat (LF) or high-fat (HF) diet in combination with sufficient (7 mg pyridoxine/kg diet) or insufficient (1 mg) amounts of vitamin B6 for 16 weeks. Analysis of microarray data revealed that expressions of 4000 genes were significantly altered by the experimental diets (LF7, LF1, HF7, and HF1). The effects of dietary fat content on gene expressions were markedly greater than vitamin B6 content. Only three differentially expressed genes (DEGs) were overlapped between the LF1/LF7 and HF1/HF7 comparison. In the LF1/LF7 comparison, 54 upregulated DEGs were enriched in gene ontology (GO) terms associated with the sterol metabolic process and 54 downregulated DEGs were enriched in GO terms associated with immune response. In HF1/HF7 comparison, 26 upregulated DEGs were enriched in GO terms associated with amino acid catabolic process. High-fat consumption downregulated gene expressions associated with vitamin B6-dependent pathways. In conclusion, our data suggest that obesity may differentially regulate vitamin B6-associated metabolic pathways in the body.

It has been reported that maternal nutrition determines the offspring’s susceptibility to chronic diseases including cancer. Here, we investigated the effects of maternal diets differing in protein source on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in adult rat offspring. Dams were fed a casein (CAS) diet or a low-isoflavone soy protein isolate (SPI) diet for two weeks before mating and throughout pregnancy and lactation. Offspring were weaned to and fed a chow diet throughout the study. From four weeks of age, hepatocellular carcinomas (HCC) were induced by intraperitoneal injection of DEN once a week for 14 weeks. The SPI/DEN group exhibited higher mortality rate, tumor multiplicity, and HCC incidence compared with the CAS/DEN group. Accordingly, altered cholesterol metabolism and increases in liver damage and angiogenesis were observed in the SPI/DEN group. The SPI/DEN group had a significant induction of the nuclear factor-κB-mediated anti-apoptotic pathway, as measured by increased phosphorylation of IκB kinase β, which may lead to the survival of precancerous hepatocytes. In conclusion, maternal consumption of a low-isoflavone soy protein isolate diet accelerated chemically induced hepatocarcinogenesis in male rat offspring in the present study, suggesting that maternal dietary protein source may be involved in DEN-induced hepatocarcinogenesis in adult offspring.