Hepatic acetogenesis and ketogenesis in neonatal swine

Reports of low circulating ketone bodies (β-hydroxybutyrate, β-OHB & acetoacetate) in suckling piglets and evidence of minimal hepatic ketone body production from fatty acids in vitro suggested that, unlike previously-studied neonates, enhanced ketogenesis does not characterize the metabolism of the newborn pig. This apparent idiosyncracy of piglet metabolism prompted a series of studies examining development and regulation of ketogenesis in piglets, and the physiological implications of low ketonemia in piglets. The extent of alternative pathways (non-ketogenic routes of carbon flux into Krebs cycle intermediates, e.g.) of fatty acid β-oxidation was also assessed. Low ketogenic capacity in piglets was confirmed by the small change in plasma (β-OHB) relative to (C8:0) (regression slope) following a dose of C8:0. This slope was 1-2 orders of magnitude lower vs. that of mature pigs and newborn or mature rabbits. Minimal fatty acid carboxyl-carbon accumulated in ketone bodies after incubations of piglet liver homogenates or hepatocytes with (1-$\sp{14}$C) -C7:0, -C8:0, or -C16:0 in vitro, consistent with the in vivo results. The observed low activity of the ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) increased plasma (insulin) with suckling (patterns opposite that seen in ketotic neonatal rats, e.g.) may in part explain attenuated ketogenic capacity in piglets. Piglets accumulated fatty acid carboxyl-carbon in acetate to a high degree relative to ketone bodies in incubations of liver tissue with radiolabeled fatty acids, a phenomenon previously unreported for any animal. It is thus speculated that acetate plays a more important physiological role than the ketone bodies in newborn piglets, an idea supported by the small contribution of ketone bodies to the energy budget of piglets ($<$3% of metabolic rate from ketone bodies at normal physiological plasma (β- OHB)), and the 10-fold higher plasma (acetate) relative to the (ketone bodies) in piglets.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Food Science and Human Nutrition

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Adams, Sean Harrison

Contributors dc:contributor

• Odle, Jack

• Biology, Animal Physiology
• Health Sciences, Nutrition

Statement dc:rights

• Copyright 1994 Adams, Sean Harrison

Language dc:language

eng

Identifier

AAI9512276
(UMI)AAI9512276

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/22459