Carvalho 2020 BMC Nutr

Carvalho E, Adams SH, Borsheim E, Blackburn ML, Ono-Moore KD, Cotter M, Bowlin AK, Yeruva L (2020) Neonatal diet impacts liver mitochondrial bioenergetics in piglets fed formula or human milk. BMC Nutr 6:13.

» Open Access

Carvalho E, Adams SH, Borsheim E, Blackburn ML, Ono-Moore KD, Cotter M, Bowlin AK, Yeruva L (2020) BMC Nutr

Abstract: 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. Such effects may be most profound in splanchnic tissues that would have early exposure to diet-associated or gut microbe-derived factors.

To 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.

No 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.

While 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. • Keywords: Human milk, Formula diet, Mitochondria Liver Gastrointestinal tract • Bioblast editor: Doerrier C • O2k-Network Lab: PT Coimbra Carvalho E, US AR Little Rock Borsheim E

Labels: MiParea: Respiration, mtDNA;mt-genetics, Developmental biology 

Organism: Pig  Tissue;cell: Liver  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS  Pathway: N, NS, ROX  HRR: Oxygraph-2k