Maternal Low-Protein Diet Modulates Glucose Metabolism and Hepatic MicroRNAs Expression in the Early Life of Offspring †

Abstract

Emerging studies revealed that maternal protein restriction was associated with increased risk of type 2 diabetes mellitus in adulthood. However, the mechanisms of its effects on offspring, especially during early life of offspring, are poorly understood. Here, it is hypothesized that impaired metabolic health in offspring from maternal low-protein diet (LPD) is associated with perturbed miRNAs expression in offspring as early as the weaning age. We examined the metabolic effects on the C57BL/6J mice male offspring at weaning from dams fed with LPD or normal chow diet (NCD) throughout pregnancy and lactation. Maternal LPD feeding impaired metabolic health in offspring. Microarray profiling indicated that mmu-miR-615, mmu-miR-124, mmu-miR-376b, and mmu-let-7e were significantly downregulated, while, mmu-miR-708 and mmu-miR-879 were upregulated in LPD offspring. Bioinformatic analysis showed target genes were mapped to inflammatory-related pathways. Serum tumor necrosis factor-α (TNF-α) levels were higher and interleukin 6 (IL-6) had a tendency to be elevated in the LPD group. Finally, both mRNA and protein levels of IL-6 and TNF-α were significantly increased in the LPD group. Our findings provide novel evidence that maternal LPD can regulate miRNAs expression, which may be associated with chronic inflammation status and metabolic health in offspring as early as the weaning age.

Association between famine exposure in early life and type 2 diabetes mellitus and hyperglycemia in adulthood: Results from the China Health And Retirement Longitudinal Study (CHARLS)

“…There are some potential mechanisms to explain the association between fetal famine exposure and T2DM and hyperglycemia in adulthood. Malnutrition in utero may lead to impaired insulin–glucose metabolism in adulthood, and even a maternal diet with low protein intake predisposes offspring to impaired glucose tolerance as early as the weaning age . Moreover, polymorphisms of genes involved in glucose and insulin metabolism may be modified by antenatal exposure to famine during mid‐gestation and can contribute to a higher prevalence of impaired glucose tolerance and T2DM later in life .…”

Maternal Nutrition and Metabolic Disorder-Related Mirnas in the Offspring

“…Several authors have already reported that maternal malnutrition during pregnancy and lactation can be harmful to the birth weight and metabolic homeostasis of the offspring [5][6][7]. Complementarily, few recent studies have demonstrated the association among maternal diet restriction, disturbances in the miRNA expression and metabolic diseases onset in life [6,7].…”

“…Complementarily, few recent studies have demonstrated the association among maternal diet restriction, disturbances in the miRNA expression and metabolic diseases onset in life [6,7]. …”

“…In fact, Zheng et al [6] showed that maternal consumption of low-protein diet during pregnancy and lactation impairs glucose tolerance and regulates the hepatic expression of different miRNAs in the mice offspring at weaning. In this study, four miRNAs (mmu-miR-615, mmu-miR-124, mmu-miR-376b and mmu-let7e) were downregulated and two miRNAs (mmu-miR-708 and mmu-miR-879) were significantly upregulated in the 21-day-old pups.…”

“…In this study, four miRNAs (mmu-miR-615, mmu-miR-124, mmu-miR-376b and mmu-let7e) were downregulated and two miRNAs (mmu-miR-708 and mmu-miR-879) were significantly upregulated in the 21-day-old pups. Inflammatory pathways (including MAPK, TGF-beta and Toll-like receptor) were associated with all these six differentiallyexpressed miRNAs and increased mRNA and protein levels of IL-6 and TNF-α were observed in the livers of the offspring exposed to maternal protein restriction during pregnancy and lactation [6].…”