Impact of Cu Source and Cu Concentration on Nutrigenomic and Ionomic Profiling in the Weanling Pig
Abstract
The overarching objectives of this research were to 1) determine the role copper (Cu) concentration on cellular proliferation and membrane damage in porcine intestinal- (IPEC-J2) and murine macrophage- (RAW267.4) cells, 2) determine the effect of dietary source and concentration Cu on transcriptional regulation of intestinal cellular metabolism, and 3) determine the effects of Cu source and concentration on ionomic profiles in the intestine, liver, kidney, serum and gall bladder contents in weanling pigs Results indicate that proliferation of IPEC-J2 and RAW267.4 cells is reduced when cells are incubated with increasing concentrations of Cu. However, intestinal cells do not exhibit membrane damage due to Cu exposure as RAW267.4 cells do. Organic and inorganic sources of Cu were utilized to determine a genome wide approach evaluating transcriptionally regulated biological impact of Cu, utilizing 71 transcripts involved in signal transduction, cell adhesion, cell cycle regulation and DNA damage and repair, including genes Erk, calcineurin A, and protein kinase. There were 3 non transcriptionally regulated transcription factors, indicated by MetaCore, which illustrated HNF4A, SP1 and ESR1 as the key regulators of altered genes within the dataset. Furthermore, feeding 25 mg/kg Cu, from either Cu proteinate or CuSO4, to weanling pigs for 14 d differentially regulated 214 transcripts in the proximal jejunum. Among which were pathways for cytoskeletan remodeling, G-protein signaling and signal transduction, and include differential regulation of a variety of transcripts including TGF-β receptor type II and MAPK9. Analysis utilizing 0, 4, 25 and 125 mg/kg Cu from both sources revealed interactions affecting concentrations of Cd & K in the liver; Cu, K, As, & Rb in the serum; and Mg, P, Ca, K, Na, B, Co, Mo, Pb & Sr in gall bladder contents. Feeding 125 mg/kg concentrations of Cu, regardless of source, decrease Mo concentrations in the PJ, increase Cu, Zn, Fe, Mg, & Cd, and increase: liver Se, Mn, & Cd; kidney Zn, Mn, Co, & Cd; serum Na, Co; and gall bladder contents of Se, & Mo. Furthermore, dietary correlations using added Cu concentrations, regardless of source, affected the ionomic mineral network of minerals (intestine: Zn, Fe, Mg, B, Cd, Mo; liver: Se, Mn, P, Na, Cd, Co; kidney: Zn, Se, Mn, Co, serum: Na, Co, Gall Bladder Contents: Se, Mn, Mo). Mineral correlation wheels were created for Cu fed in the range between 4 and 125 mg/kg. This data provides unique and novel evidence regarding the role Cu source and concentration impacts the intestinal transcriptome and gene expression associated with Cu induced biological functions, and how Cu differentially affects mineral network dynamics in various tissues of the weanling pig.
Degree
Ph.D.
Advisors
Radcliffe, Purdue University.
Subject Area
Animal sciences
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