(P06-019-24) Medium-Chain Fatty Acid Rich Formula Causes Hepatic Steatosis by 7 Days and Progresses to Nonalcoholic Steatohepatitis by 14 Days in Neonatal Pigs

Objectives: We previously reported that feeding medium-chain fatty acids (MCFA) for 21 d resulted in panacinar steatosis with concomitant changes in the expression of fatty acid metabolic enzymes in neonatal pigs. The objectives of this study were to investigate the onset of steatosis and the temporal changes in transcript abundance of enzymes related to fat metabolism.

Methods: Pigs (n=18) were fed isocaloric formulas containing either MCFA or long-chain fatty acids (LCFA). Pigs were sacrificed on days 7, 14, or 21.

Results: Microscopic evaluation of liver sections revealed periportal macrovesicular steatosis as early as 7 d in pigs fed MCFA that progressed into panacinar steatosis at 14 and 21 d compared with those fed LCFA. In addition, steatosis grade, ballooning, and lobular inflammation were greater in pigs fed MCFA indicating early-stage non-alcoholic fatty liver disease developing at 7 d and progressing into non-alcoholic steatohepatitis at 14 and 21 d compared with those fed the LCFA formula. Transcript abundance of fatty acid synthase, elongase 5, peroxisome proliferator-activated receptor alpha, acyl-CoA synthase long chain member 1, carnitine palmitoyl transferase 1, acyl-CoA dehydrogenase for long chain, superoxide dismutase 1 were greater for MCFA compared with LCFA group. Oxidation of laurate was greater for pigs fed the MCFA compared with those fed the LCFA formula.

Conclusions: These data suggest that MCFA feeding upregulated fatty acid synthetic, oxidative, and elongation pathways. It is likely that steatosis occurred as a result of lipogenesis or fatty acid elongation despite an upregulation of fatty acid oxidation.

Funding Sources: None