Regulation of carnitine palmitoyltransferase activity in the liver and brown adipose tissue in the newborn rat: Effect of starvation and hypothermia

Peñas, Matilde Santos; Benito, Manuel

doi:10.1016/0006-291x(86)90034-3

Cited by 17 publications

(10 citation statements)

References 17 publications

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“…Despite these transcriptional increases in Cpt enzymes, we observed no significant changes in heart Cpt enzyme activity. Cpt enzyme activities have been reported to increase with increasing mitochondrial L-carnitine levels [38-40]. Unfortunately, L-carnitine levels in the whole heart tissue rather than in the mitochondria were measured in our study.…”

Section: Discussionmentioning

confidence: 81%

Systematic Evaluation of Key L-Carnitine Homeostasis Mechanisms during Postnatal Development in Rat

2012

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BackgroundThe conditionally essential nutrient, L-carnitine, plays a critical role in a number of physiological processes vital to normal neonatal growth and development. We conducted a systematic evaluation of the developmental changes in key L-carnitine homeostasis mechanisms in the postnatal rat to better understand the interrelationship between these pathways and their correlation to ontogenic changes in L-carnitine levels during postnatal development.MethodsmRNA expression of heart, kidney and intestinal L-carnitine transporters, liver γ-butyrobetaine hydroxylase (Bbh) and trimethyllysine hydroxylase (Tmlh), and heart carnitine palmitoyltransferase (Cpt) were measured using quantitative RT-PCR. L-Carnitine levels were determined by HPLC-UV. Cpt and Bbh activity were measured by a spectrophotometric method and HPLC, respectively.ResultsSerum and heart L-carnitine levels increased with postnatal development. Increases in serum L-carnitine correlated significantly with postnatal increases in renal organic cation/carnitine transporter 2 (Octn2) expression, and was further matched by postnatal increases in intestinal Octn1 expression and hepatic γ-Bbh activity. Postnatal increases in heart L-carnitine levels were significantly correlated to postnatal increases in heart Octn2 expression. Although cardiac high energy phosphate substrate levels remained constant through postnatal development, creatine showed developmental increases with advancing neonatal age. mRNA levels of Cpt1b and Cpt2 significantly increased at postnatal day 20, which was not accompanied by a similar increase in activity.ConclusionsSeveral L-carnitine homeostasis pathways underwent significant ontogenesis during postnatal development in the rat. This information will facilitate future studies on factors affecting the developmental maturation of L-carnitine homeostasis mechanisms and how such factors might affect growth and development.

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Section: Discussionmentioning

confidence: 81%

Systematic Evaluation of Key L-Carnitine Homeostasis Mechanisms during Postnatal Development in Rat

2012

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“…In most mammalian species, a physiological hyperketonaemia develops during the first 24 h after birth [1] as the result of an increased capacity for hepatic fatty acid oxidation [2]. In the newborn rat or rabbit, the development of the capacity for hepatic long-chain fatty acid (LCFA) oxidation seems to be partly regulated by a fall in the malonyl-CoA concentration and by a decrease in the sensitivity of carnitine palmitoyltransferase I (CPT I) to inhibition by malonyl-CoA [3][4][5][6]. In the adult rat liver it has been shown that a linear relationship exists between the hepatic malonyl-CoA concentration and the sensitivity of CPT I to malonyl-CoA inhibition in many physiological situations [7].…”

Section: Introductionmentioning

confidence: 99%

“…Such a mechanism of regulation can be questioned during the neonatal period or at the suckling-weaning transition in the rat or the rabbit [4][5][6]13]. In hepatocytes from newborn rats [4,5] and rabbits [6], or from rats weaned on different diets [13], it was shown that LCFA oxidation was mainly regulated through changes in the sensitivity of CPT I to malonyl-CoA inhibition rather than through changes in the malonyl-CoA levels. It has been shown recently that exposure of cultured fetal rabbit hepatocytes to glucagon or cyclic AMP for 48 h decreased the sensitivity of CPT I to malonyl-CoA inhibition and induced LCFA oxidation [14].…”

Section: Introductionmentioning

confidence: 99%

Evidence that the sensitivity of carnitine palmitoyltransferase I to inhibition by malonyl-CoA is an important site of regulation of hepatic fatty acid oxidation in the fetal and newborn rabbit. Perinatal development and effects of pancreatic hormones in cultured rabbit hepatocytes

Prip‐Buus

Pégorier

Duée

et al. 1990

Biochemical Journal

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The temporal changes in oleate oxidation, lipogenesis, malonyl-CoA concentration and sensitivity of carnitine palmitoyltransferase I (CPT 1) to malonyl-CoA inhibition were studied in isolated rabbit hepatocytes and mitochondria as a function of time after birth of the animal or time in culture after exposure to glucagon, cyclic AMP or insulin. (1) Oleate oxidation was very low during the first 6 h after birth, whereas lipogenesis rate and malonyl-CoA concentration decreased rapidly during this period to reach levels as low as those found in 24-h-old newborns that show active oleate oxidation. (2) The changes in the activity of CPT I and the IC50 (concn. causing 50% inhibition) for malonyl-CoA paralleled those of oleate oxidation. (3) In cultured fetal hepatocytes, the addition of glucagon or cyclic AMP reproduced the changes that occur spontaneously after birth. A 12 h exposure to glucagon or cyclic AMP was sufficient to inhibit lipogenesis totally and to cause a decrease in malonyl-CoA concentration, but a 24 h exposure was required to induce oleate oxidation. (4) The induction of oleate oxidation by glucagon or cyclic AMP is triggered by the fall in the malonyl-CoA sensitivity of CPT I. (5) In cultured hepatocytes from 24 h-old newborns, the addition of insulin inhibits no more than 30% of the high oleate oxidation, whereas it stimulates lipogenesis and increases malonyl-CoA concentration by 4-fold more than in fetal cells (no oleate oxidation). This poor effect of insulin on oleate oxidation seems to be due to the inability of the hormone to increase the sensitivity of CPT I sufficiently. Altogether, these results suggest that the malonyl-CoA sensitivity of CPT I is the major site of regulation during the induction of fatty acid oxidation in the fetal rabbit liver.

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“…Recently, we have assessed the kinetic constants of CPT I from javelin goby Synechogobius hasta (Zheng et al 2013a, b;Tan et al 2013) and grass carp (Zheng et al 2013a, b). However, studies regarding CPT I kinetics with different stages of growth and development have mainly been limited to mammals, such as rats (Girard et al 1985;Peñas and Benito 1986), rabbits (Herbin et al 2005), pigs (Bieber et al 1973;Lin and Odle 1995), canine (Lin and Odle 2003) and feline (Lin et al 2005). In fish, Liu et al (2014) investigated CPT I kinetics of Chinese sucker under different developmental stages, and they pointed out that extrapolation of findings from mammalian model to other species must be done cautiously because fish show peculiar idiosyncrasies related to lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

Ontogeny and kinetics of carnitine palmitoyltransferase I in hepatopancreas and skeletal muscle of grass carp (Ctenopharyngodon idella)

Luo

Mai

et al. 2015

Fish Physiol Biochem

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The ontogeny and kinetics of carnitine palmitoyltransferase I (CPT I) were investigated in hepatopancreas and muscle throughout four developmental stages (newly hatched larvae, 1-month-old juvenile, 3-month-old, and 6-month-old, respectively) of grass carp Ctenopharyngodon idella. In hepatopancreas, the maximal velocity (Vmax) significantly increased from hatching to 1-month-old grass carp and then gradually declined at 6-month-old grass carp. In muscle, CPT I activity was the highest at 1-month-old grass carp, nearly twofold higher than that at hatching (P < 0.05). The Michaelis constant (Km) value was also the highest for 1-month-old in both tested tissues. Carnitine concentrations (FC, AC and TC) were the lowest for 3-month-old grass carp and remained relatively constant in both tissues from fish under the other developmental stages. The FC concentration in hepatopancreas and muscle at four developmental stages were less than the respective Km, indicating that grass carp required supplemental carnitine in their food to ensure that CPT I activity was not constrained by carnitine availability.

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Regulation of carnitine palmitoyltransferase activity in the liver and brown adipose tissue in the newborn rat: Effect of starvation and hypothermia

Cited by 17 publications

References 17 publications

Systematic Evaluation of Key L-Carnitine Homeostasis Mechanisms during Postnatal Development in Rat

Systematic Evaluation of Key L-Carnitine Homeostasis Mechanisms during Postnatal Development in Rat

Evidence that the sensitivity of carnitine palmitoyltransferase I to inhibition by malonyl-CoA is an important site of regulation of hepatic fatty acid oxidation in the fetal and newborn rabbit. Perinatal development and effects of pancreatic hormones in cultured rabbit hepatocytes

Ontogeny and kinetics of carnitine palmitoyltransferase I in hepatopancreas and skeletal muscle of grass carp (Ctenopharyngodon idella)

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