Fetal Hepatic and Neural Substrate Utilization as Affected by Induced Nutritional Ketosis in Swine

Steele, N. C.; Rosebrough, R. W.; McMurtry, J. P.

doi:10.2527/jas1984.5861388x

Cited by 6 publications

(4 citation statements)

References 23 publications

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“…When ketosis was induced by an over-night fast, the neonatal lamb myocardium increased its β OHB oxidation in response to the increase in ketone supply. A similar increase in β OHB oxidation was reported in the brain of the swine fetus following maternal ketosis [36]. In the fetal pig, the brain was also found to increase in weight, protein content and cell size following maternal ketosis [37].…”

Section: Discussionsupporting

confidence: 63%

“…Unlike the heart and brain, the fetal liver has been reported to only increase its rate of lipogenesis, but not its rate of β OHB oxidation (i.e. degradation), during maternal ketosis [36]. The potential implication of this is a more rapid triglyceride synthesis, but with a preference for fat deposition in the liver, that could result in an increase in hepatic volume.…”

Section: Discussionmentioning

confidence: 99%

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Effects of a ketogenic diet during pregnancy on embryonic growth in the mouse

Sussman

Eede

Wong

et al. 2013

BMC Pregnancy Childbirth

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BackgroundThe increasing use of the ketogenic diet (KD), particularly by women of child-bearing age, raises a question about its suitability during gestation. To date, no studies have thoroughly investigated the direct implications of a gestational ketogenic diet on embryonic development.MethodsTo fill this knowledge gap we imaged CD-1 mouse embryos whose mothers were fed either a Standard Diet (SD) or a KD 30 days prior to, as well as during gestation. Images were collected at embryonic days (E) 13.5 using Optical Projection Tomography (OPT) and at E17.5 using Magnetic Resonance Imaging (MRI).ResultsAn anatomical comparison of the SD and KD embryos revealed that at E13.5 the average KD embryo was volumetrically larger, possessed a relatively larger heart but smaller brain, and had a smaller pharynx, cervical spinal cord, hypothalamus, midbrain, and pons, compared with the average SD embryo. At E17.5 the KD embryo was found to be volumetrically smaller with a relatively smaller heart and thymus, but with enlarged cervical spine, thalamus, midbrain and pons.ConclusionA ketogenic diet during gestation results in alterations in embryonic organ growth. Such alterations may be associated with organ dysfunction and potentially behavioral changes in postnatal life.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Effects of a ketogenic diet during pregnancy on embryonic growth in the mouse

Sussman

Eede

Wong

et al. 2013

BMC Pregnancy Childbirth

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“…Thus, plasma acetate could be largely derived metabolically from hepatic mitochondrial fatty acid oxidation and/or from pyruvate dehydrogenase and distributed to other tissues for utilization. Acetate is preferentially metabolized (over ketone bodies) in pig liver, brain, and colonocytes (7,36), suggesting it is an important physiological fuel. In addition, the production and distribution of acetate may be important for lipogenesis, which occurs primarily in adipose tissue in swine due to the extremely low hepatic lipogenesis (26).…”

Section: Discussionmentioning

confidence: 99%

Carnitine palmitoyltransferase I control of acetogenesis, the major pathway of fatty acid β-oxidation in liver of neonatal swine

Lin

Shim

Odle

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Lin X, Shim K, Odle J. Carnitine palmitoyltransferase I control of acetogenesis, the major pathway of fatty acid ␤-oxidation in liver of neonatal swine. Am J Physiol Regul Integr Comp Physiol 298: R1435-R1443, 2010. First published March 17, 2010 doi:10.1152/ajpregu.00634.2009.-To examine the regulation of hepatic acetogenesis in neonatal swine, carnitine palmitoyltransferase I (CPT I) activity was measured in the presence of varying palmitoyl-CoA (substrate) and malonyl-CoA (inhibitor) concentrations, and [1-14 C]-palmitate oxidation was simultaneously measured. Accumulation rates of 14 C-labeled acetate, ketone bodies, and citric acid cycle intermediates within the acid-soluble products were determined using radio-HPLC. Measurements were conducted in mitochondria isolated from newborn, 24-h (fed or fasted), and 5-mo-old pigs. Acetate rather than ketone bodies was the predominant radiolabeled product, and its production increased twofold with increasing fatty acid oxidation during the first 24-h suckling period. The rate of acetogenesis was directly proportional to CPT I activity. The high activity of CPT I in 24-h-suckling piglets was not attributable to an increase in CPT I gene expression, but rather to a large decrease in the sensitivity of CPT I to malonyl-CoA inhibition, which offset a developmental decrease in affinity of CPT I for palmitoyl-CoA. Specifically, the IC 50 for malonyl-CoA inhibition and Km value for palmitoyl-CoA measured in 24-h-suckling pigs were 1.8-and 2.7-fold higher than measured in newborn pigs. The addition of anaplerotic carbon from malate (10 mM) significantly reduced 14 C accumulation in acetate (P Ͻ 0.003); moreover, the reduction was much greater in newborn (80%) than in 24-h-fed (72%) and 5-mo-old pigs (55%). The results demonstrate that acetate is the primary product of hepatic mitochondrial ␤-oxidation in Sus scrofa and that regulation during early development is mediated primarily via kinetic modulation of CPT I. acetate; anaplerosis; carnitine palmitoyltransferase I activity; ketone bodies; mitochondria; Sus scrofa IT IS WELL ESTABLISHED THAT hepatic long-chain fatty acid oxidation is acutely controlled by a system in which carnitine palmitoyltransferase I (CPT I) is regulated allosterically by a change in malonyl-CoA concentration and/or the sensitivity to malonyl-CoA inhibition. This regulatory mechanism dictates fatty acid flux into mitochondria and controls the rates of ␤-oxidation and ketogenesis based on the animal's physiological status. The neonatal period represents a physiological state characterized by marked enhancement of fatty acid oxidation and ketogenesis. Both humans and rats present a significant hyperketonemia during the suckling period (40). Evidence confirms that the physiological hyperketonemia is a result of the high hepatic ketogenic rate in neonates consuming a diet (i.e., milk) that is high in fat and low in carbohydrate. In fact, more than 90% of the non-CO 2 carbon derived from fatty acid oxidation in liver homogenates is ketone bodies (21). Wh...

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“…Furthermore, a positive relation of acetogenic activity with non-esterified fatty acid (NEFA) availability is observed, when fasted and fed individuals are compared. It can be concluded that acetate is the primary product of mitochondrial oxidation in pig; consequently the preferred substrate in porcine liver, brain and intestine and early regulation is brought about by kinetic CPT-1 inhibition (Steele et al, 1984;Darcy-Vrillon et al, 1996). Boyd et al (1982) showed different patterns for NEFA oxidation.…”

Section: Energy Demandmentioning

confidence: 99%

Intrinsic challenges of neonatal adaptation in swine

et al. 2022

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Abstract. The losses of piglets in commercial pig farming remain at concerning levels and need to be addressed through the implementation of new sustainable breeding and management strategies. In fact, piglets are especially at risk in the first days of life. Both genetics and the farrowing process have been shown to impact piglet vitality. In addition, knowledge of the animal-intrinsic responses in adapting to extra-uterine life is particularly important but is scarcely described in the scientific literature. In this review, the three phases that constitute neonatal adaptation in the pig are systematically presented. The first phase of early adaptation involves primarily the development of cardiorespiratory function (within the first 10 min of life) as well as thermoregulatory processes and acid–base balance (up to 24 h of life). In the second phase, homeostasis is established, and organ maturation takes place (up to 14 d post natum). The final third phase aims at the development of neurological, immunological and muscular features (up to 28 d of life). The involvement of aggravating and ameliorating factors such as dystocia, low colostrum yield and heat supply is key to the development of strategies to reduce piglet losses and increase vitality. The insights are of particular value in addressing current concerns in pig farming and to further improve animal welfare in pig production across different management types.

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Fetal Hepatic and Neural Substrate Utilization as Affected by Induced Nutritional Ketosis in Swine

Cited by 6 publications

References 23 publications

Effects of a ketogenic diet during pregnancy on embryonic growth in the mouse

Effects of a ketogenic diet during pregnancy on embryonic growth in the mouse

Carnitine palmitoyltransferase I control of acetogenesis, the major pathway of fatty acid β-oxidation in liver of neonatal swine

Intrinsic challenges of neonatal adaptation in swine

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