Neonatal diet impacts liver mitochondrial bioenergetics in piglets fed formula or human milk

Eugenia Carvalho,Sean H Adams,Michael L Blackburn,Kikumi D Ono-Moore,Elisabet Børsheim,Matthew Cotter,Laxmi Yeruva,Anne K Bowlin

doi:10.1186/s40795-020-00338-7

Abstract

BackgroundNeonatal diet impacts many physiological systems and can modify risk for developing metabolic disease and obesity later in life. Less well studied is the effect of postnatal diet (e.g., comparing human milk (HM) or milk formula (MF) feeding) on mitochondrial bioenergetics. Such effects may be most profound in splanchnic tissues that would have early exposure to diet-associated or gut microbe-derived factors.MethodsTo address this question, we measured ileal and liver mitochondrial bioenergetics phenotypes in male piglets fed with HM or MF from day 2 to day 21 age. Ileal and liver tissue were processed for mitochondrial respiration (substrate only [pyruvate, malate, glutamate], substrate + ADP, and proton “leak” post-oligomycin; measured by Oroboros methods), mitochondrial DNA (mtDNA) and metabolically-relevant gene expression analyses.ResultsNo differences between the diet groups were observed in mitochondrial bioenergetics indices in ileal tissue. In contrast, ADP-dependent liver Complex I-linked OXPHOS capacity and Complex I + II-linked OXPHOS capacity were significantly higher in MF animals relative to HM fed piglets. Interestingly, p53, Trap1, and Pparβ transcript abundances were higher in MF-fed relative to HM-fed piglets in the liver. Mitochondrial DNA copy numbers (normalized to nuclear DNA) were similar within-tissue regardless of postnatal diet, and were ~ 2–3 times higher in liver vs. ileal tissue.ConclusionWhile mechanisms remain to be identified, the data indicate that neonatal diet can significantly impact liver mitochondrial bioenergetics phenotypes, even in the absence of a change in mtDNA abundance. Since permeabilized liver mitochondrial respiration was increased in MF piglets only in the presence of ADP, it suggests that formula feeding led to a higher ATP turnover. Specific mechanisms and signals involved with neonatal diet-associated differences in liver bioenergetics remain to be elucidated.

Highlights

Neonatal diet impacts many physiological systems and can modify risk for developing metabolic disease and obesity later in life
Recent studies have reported that milk formula-fed (MF) infants present more rapid weight gain during the first weeks of life compared to breastfed infants, and this appears to be associated with weight gain later in life [3,4,5]
They speculated that diet-associated changes in microbiota and increased short chain fatty acid in human milk (HM)- and donkey milk (DM)-fed animals contributed to the differences in metabolism and mitochondrial function through as-yet unknown signaling pathways [12]

Summary

Introduction

Neonatal diet impacts many physiological systems and can modify risk for developing metabolic disease and obesity later in life. Less well studied is the effect of postnatal diet (e.g., comparing human milk (HM) or milk formula (MF) feeding) on mitochondrial bioenergetics. The nutrient composition of human milk (HM) in comparison to milk formulas may play a significant role in the observed metabolic outcomes and the reported health differences when comparing these two neonatal diets [6,7,8,9,10,11]. The authors speculated that this could contribute to burning of fat and protect the animals from developing certain obesityassociated metabolic and inflammatory sequelae They speculated that diet-associated changes in microbiota and increased short chain fatty acid (butyrate) in HM- and DM-fed animals contributed to the differences in metabolism and mitochondrial function through as-yet unknown signaling pathways [12]. We have reported significant alterations in the bioregional gut microbiome when comparing HM- and MF-fed piglets [14], and several studies have indicated differences in gut microbiota comparing breastfed to formula-fed infants [15,16,17,18]

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Conclusion