@article{zhao_pike_huang_feng_odle_lin_2023, title={Effects of medium chain triglycerides on hepatic fatty acid oxidation in clofibrate-fed newborn piglets}, volume={12}, ISSN={["2405-6545"]}, url={https://doi.org/10.1016/j.aninu.2022.12.001}, DOI={10.1016/j.aninu.2022.12.001}, abstractNote={To investigate whether increasing tricarboxylic acid (TCA) cycle activity and ketogenic capacity would augment fatty acid (FA) oxidation induced by the peroxisome proliferator-activated receptor-alpha (PPARα) agonist clofibrate, suckling newborn piglets (n = 54) were assigned to 8 groups following a 2 ( ± clofibrate) × 4 (glycerol succinate [SUC], triglycerides of 2-methylpentanoic acid [T2M], valeric acid [TC5] and hexanoic acid [TC6]) factorial design. Each group was fed an isocaloric milk formula containing either 0% or 0.35% clofibrate (wt/wt, dry matter basis) with 5% SUC, T2M, TC5 or TC6 for 5 d. Another 6 pigs served as newborn controls. Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using [1-14C] palmitic acid (1 mM) as a substrate (0.265 μCi/μmol). Measurements were performed in the absence or presence of L-carnitine (1 mM) or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase (L659699, 1.6 μM) or acetoacetate-CoA deacylase (iodoacetamide, 50 μM). Without clofibrate stimulation, 14C accumulation in CO2 was higher from piglets fed diets containing T2M and TC5 than SUC, but similar to those fed TC6. Under clofibrate stimulation, accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments. Interactions between clofibrate and carnitine or the inhibitors were observed (P = 0.0004) for acid soluble products (ASP). In vitro addition of carnitine increased 14C-ASP (P < 0.0001) above all other treatments, regardless of clofibrate treatment. The percentage of 14C in CO2 was higher (P = 0.0023) in TC5 than in the control group. From these results we suggest that dietary supplementation of anaplerotic and ketogenic FA could impact FA oxidation and modify the metabolism of acetyl-CoA (product of β-oxidation) via alteration of TCA cycle activity, but the modification has no significant impact on the hepatic FA oxidative capacity induced by PPARα. In addition, the availability of carnitine is a critical element to maintain FA oxidation during the neonatal period.}, journal={ANIMAL NUTRITION}, author={Zhao, Jinan and Pike, Brandon and Huang, Jin and Feng, Zhihua and Odle, Jack and Lin, Xi}, year={2023}, month={Mar}, pages={334–344} }
 @article{pike_zhao_hicks_wang_hagen_liu_odle_lin_2023, title={Intestinal Carnitine Status and Fatty Acid Oxidation in Response to Clofibrate and Medium-Chain Triglyceride Supplementation in Newborn Pigs}, volume={24}, ISSN={["1422-0067"]}, url={https://doi.org/10.3390/ijms24076066}, DOI={10.3390/ijms24076066}, abstractNote={To investigate the role of peroxisome proliferator-activated receptor alpha (PPARα) in carnitine status and intestinal fatty acid oxidation in neonates, a total of 72 suckled newborn piglets were assigned into 8 dietary treatments following a 2 (±0.35% clofibrate) × 4 (diets with: succinate+glycerol (Succ), tri-valerate (TC5), tri-hexanoate (TC6), or tri-2-methylpentanoate (TMPA)) factorial design. All pigs received experimental milk diets with isocaloric energy for 5 days. Carnitine statuses were evaluated, and fatty acid oxidation was measured in vitro using [1-14C]-palmitic acid (1 mM) as a substrate in absence or presence of L659699 (1.6 µM), iodoacetamide (50 µM), and carnitine (1 mM). Clofibrate increased concentrations of free (41%) and/or acyl-carnitine (44% and 15%) in liver and plasma but had no effects in the intestine. The effects on carnitine status were associated with the expression of genes involved in carnitine biosynthesis, absorption, and transportation. TC5 and TMPA stimulated the increased fatty acid oxidation rate induced by clofibrate, while TC6 had no effect on the increased fatty acid oxidation induced by clofibrate (p > 0.05). These results suggest that dietary clofibrate improved carnitine status and increased fatty acid oxidation. Propionyl-CoA, generated from TC5 and TMPA, could stimulate the increased fatty acid oxidation rate induced by clofibrate as anaplerotic carbon sources.}, number={7}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Pike, Brandon and Zhao, Jinan and Hicks, Julie A. and Wang, Feng and Hagen, Rachel and Liu, Hsiao-Ching and Odle, Jack and Lin, Xi}, year={2023}, month={Apr} }
 @article{hicks_pike_liu_2022, title={Alterations in hepatic mitotic and cell cycle transcriptional networks during the metabolic switch in broiler chicks}, volume={13}, ISSN={["1664-042X"]}, DOI={10.3389/fphys.2022.1020870}, abstractNote={During embryonic life, chicks mainly derive energy from hepatic oxidation of yolk lipids. After hatch, chicks must rely on carbohydrate-rich feed to obtain energy. This requires an abrupt and intensive switch of metabolic processes, particularly in the liver. We recently identified a number of transcriptional and post-transcriptional regulatory networks that work concordantly to tune metabolic processes during the metabolic switch. Here, we used delayed feeding post-hatch (48 h) to impede the metabolic switch in broilers. We used RNA-seq to identify hepatic transcriptome differences between late stage embryos (E18) and two-day-old chicks (D2), which were either fed-from-hatch (FED) or not fed (DLY). Between FED and E18, 2,430 genes were differentially expressed (fold-change≥ 2; FDR p-value 0.05), of these 1,237 were downregulated in FED birds and 1,193 were upregulated. Between DLY and E18, 1979 genes were differentially expressed, of these 1,043 were downregulated and 936 were upregulated in DLY birds. Between DLY and FED, 880 genes were differentially expressed, of these 543 were downregulated and 337 were upregulated in DLY birds. We found that in addition to disturbances in a number of metabolic pathways, unfed chicks had a widespread suppression of gene networks associated with cell proliferation, cell cycle progression and mitosis. Expression patterns suggest that hepatocytes of delayed-fed birds have abnormal mitosis and increased polyploidization. This suggests that post-hatch feed consumption maintains the rate and integrity of liver growth immediately, which in turn, likely helps facilitate the appropriate programming of hepatic metabolic networks.}, journal={FRONTIERS IN PHYSIOLOGY}, author={Hicks, Julie A. and Pike, Brandon E. and Liu, Hsiao-Ching}, year={2022}, month={Oct} }