Caloric Intake Affects Neonatal Bone Development and Energy Metabolism
Authors: Zhang Wei , Murray Robert , Barkley Grace , Singh Nikki , Rhoads Robert P. , Stahl Chad H. 
Published: June 2021

Deficits in bone deposition during early‐life increases risk of osteoporosis later in life. Bone marrow mesenchymal stem cells (MSC) are a subset of multipotent stem cells residing within the bone which provide the life‐long supply of bone forming cells. Our previous work has revealed that the activity and differentiation potential of MSC are subject to alteration based on neonatal nutrition. With increasing interest in metabolic disorders and an increasing incidence of bone diseases, we aimed to elucidate the impact of dietary energy restriction and excess on the activity and differentiation potential of MSC during neonatal development. During a 16‐day study, 30 neonatal pigs (24±6h old) were fed with milk replacers that were isonitrogenous, but either 25% restricted (R), adequate (A), or 25% in excess (E) of energy requirements through the adjustment of dietary fat and lactose levels. Piglets were fed 8 times/d at a rate to match the growth rate of sow‐reared piglets. Body weight and feed intake were recorded daily. At the end of the study, humeri were collected for the isolation of MSC and radial/ulna bones were collected for physical measurement and determination of bone mineral content. Fat and liver tissues were collected for gene expression analysis. Dietary energy level did not impact body weight (BW) during the study (4.40±0.35 kg final BW). The energy restricted group had 7.5% greater bone mineral content than the E group (R: 37.66±0.36, A: 35.56±0.41, E: 35.02±0.41. P<0.05), but bone cross‐sectional area was not different between treatments. No difference was found in both in vivo and in vitro MSC proliferation as determined by BrDU labeling and EDU straining respectively. Assays to examine the in vitro differentiation potential of the MSC, suggested that MSC isolated from the R piglets were more primed towards an osteogenic lineage than those from the other treatments, and this was featured by greater expression of osteocalcin and fibronectin (P<0.05). However, no difference in adipocytic differentiation potential was seen based on dietary treatment. Gene expression analysis in subcutaneous fat suggests that excess energy diet promoted lipogenesis via the increased expression of fatty acid synthesis (FAS) and acyl‐CoA carboxylase (ACC). In the liver, excess energy increased the expression of carnitine palmitoyltransferae I (CPT1), peroxisome proliferator‐activated receptor alpha (PPARα), and oxidative stress responsive kinase I (OXSR1), glutathione peroxidase 3 (GPX3) but decreased the expression of FAS. These data suggested that excessive energy consumption during the neonatal period may compromise bone integrity, will promote lipid accumulation in subcutaneous fat, and will induce oxidative stress.Support or Funding InformationThe project is funded by USDA with the access number: 2015‐67015‐25094.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.