Adaptations of glucose and fatty acid metabolism during perinatal period and suckling-weaning transition

Girard, Jean; Ferré, Pascal; Pégorier, Jean‐Paul; Duée, Pierre‐Henri

doi:10.1152/physrev.1992.72.2.507

Cited by 462 publications

(378 citation statements)

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“…By contrast, the level of CPT I1 mRNA and the activity of the enzyme are already high prior to birth and remain constant during suckling and weaning regardless of the fat content of the solid diet [92, 931. All of these findings are consistent with earlier reports that during the fetalneonatal transition, not only is the activity of CPT I increased but both the liver content of malonyl-CoA and sensitivity of CPT I to malonyl-CoA inhibition are markedly decreased, allowing for efficient fatty acid oxidation and ketone body production (reviewed in [94]). Conversely, with weaning onto a high carbohydrate diet all of these parameters ar reversed [92-941. In the rat intestine the pattern of CPT I and CPT I1 gene expression during the perinatal period, as well as that for mitochondrial hydroxymethylglutaryl-CoA synthase (which mirrors the CPT I profile), are very similar to those found in liver [93], consistent with a ketogenic role for the intestine at this time [93, 951. The factors responsible for turning on the liver CPT I gene at birth have recently been examined using cultured hepatocytes from 20-day-old fetal rats [96].…”

Section: Structuresupporting

confidence: 92%

The Mitochondrial Carnitine Palmitoyltransferase System — From Concept to Molecular Analysis

McGarry

Brown

1997

European Journal of Biochemistry

1,462

1,220

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First conceptualized as a mechanism for the mitochondrial transport of long-chain fatty acids in the early 1960s, the carnitine palmitoyltransferase (CPT) system has since come to be recognized as a pivotal component of fuel homeostasis. This is by virtue of the unique sensitivity of the outer membrane CPT I to the simple molecule, malonyl-CoA. In addition, both CPT I and the inner membrane enzyme, CPT 11, have proved to be loci of inherited defects, some with disastrous consequences. Early efforts using classical approaches to characterize the CPT proteins in terms of structure/function/regulatory relationships gave rise to confusion and protracted debate. By contrast, recent application of molecular biological tools has brought major enlightenment at an exponential pace. Here we review some key developments of the last 20 years that have led to our current understanding of the physiology of the CPT system, the structure of the CPT isofornis, the chromosomal localization of their respective genes, and the identification of mutations in the human population.

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Section: Structuresupporting

confidence: 92%

The Mitochondrial Carnitine Palmitoyltransferase System — From Concept to Molecular Analysis

McGarry

Brown

1997

European Journal of Biochemistry

1,462

1,220

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“…However, the difference in proliferation rates was not seen when the mice were weaned on a high-fat, carbohydrate-free diet. Thus, during the weaning period, when there is a high rate of beta cell proliferation [69] and when the diet changes from a lipid-rich milk to a carbohydrate-rich chow [70], GLUT2-dependent nervous glucose sensing and parasympathetic activity play a critical role in stimulating beta cell proliferation to achieve normal adult beta cell mass.…”

Section: Nervous Glucose Sensing and The Regulation Of Islet Cell Masmentioning

confidence: 99%

GLUT2, glucose sensing and glucose homeostasis

2014

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The glucose transporter isoform GLUT2 is expressed in liver, intestine, kidney and pancreatic islet beta cells, as well as in the central nervous system, in neurons, astrocytes and tanycytes. Physiological studies of genetically modified mice have revealed a role for GLUT2 in several regulatory mechanisms. In pancreatic beta cells, GLUT2 is required for glucose-stimulated insulin secretion. In hepatocytes, suppression of GLUT2 expression revealed the existence of an unsuspected glucose output pathway that may depend on a membrane traffic-dependent mechanism. GLUT2 expression is nevertheless required for the physiological control of glucose-sensitive genes, and its inactivation in the liver leads to impaired glucose-stimulated insulin secretion, revealing a liver-beta cell axis, which is likely to be dependent on bile acids controlling beta cell secretion capacity. In the nervous system, GLUT2-dependent glucose sensing controls feeding, thermoregulation and pancreatic islet cell mass and function, as well as sympathetic and parasympathetic activities. Electrophysiological and optogenetic techniques established that Glut2 (also known as Slc2a2)-expressing neurons of the nucleus tractus solitarius can be activated by hypoglycaemia to stimulate glucagon secretion. In humans, inactivating mutations in GLUT2 cause Fanconi-Bickel syndrome, which is characterised by hepatomegaly and kidney disease; defects in insulin secretion are rare in adult patients, but GLUT2 mutations cause transient neonatal diabetes. Genome-wide association studies have reported that GLUT2 variants increase the risks of fasting hyperglycaemia, transition to type 2 diabetes, hypercholesterolaemia and cardiovascular diseases. Individuals with a missense mutation in GLUT2 show preference for sugar-containing foods. We will discuss how studies in mice help interpret the role of GLUT2 in human physiology.

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“…Indeed, newborn mammals are fed with milk, which in most species is a high-fat low-carbohydrate diet (Jenness, 1974). Moreover, in some species (rabbit, guinea-pig, human), fatty acids also originate from adipose triacylglycerol stores that are mobilized immediately after birth (Girard et al, 1992). Then fatty acid oxidation develops rapidly after birth in many peripheral tissues and in the liver, where fatty acids are used as precursors for ketone-body synthesis (Williamson, 1982).…”

Section: Introductionmentioning

confidence: 99%

“…Then fatty acid oxidation develops rapidly after birth in many peripheral tissues and in the liver, where fatty acids are used as precursors for ketone-body synthesis (Williamson, 1982). As a direct consequence, the concentration of blood ketone bodies increases during day 1 after birth in many newborn mammals (Williamson, 1982;Girard et al, 1992). This physiological hyperketonaemia persists during all the suckling period and decreases progressively when young mammals begin to nibble the high-carbohydrate diet ofthe adult (Williamson, 1982;Girard et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

“…As a direct consequence, the concentration of blood ketone bodies increases during day 1 after birth in many newborn mammals (Williamson, 1982;Girard et al, 1992). This physiological hyperketonaemia persists during all the suckling period and decreases progressively when young mammals begin to nibble the high-carbohydrate diet ofthe adult (Williamson, 1982;Girard et al, 1992). These co-ordinated changes are essential for the newborn to cover its energy needs, as demonstrated by the dramatic consequences of inborn errors of mitochondrial fatty acid oxidation (Turnbull et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

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Hepatic ketogenesis in newborn pigs is limited by low mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity

Duée

Pégorier

Quant

et al. 1994

Biochemical Journal

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In newborn-pig hepatocytes, the rate of oleate oxidation is extremely low, despite a very low malonyl-CoA concentration. By contrast, the sensitivity of carnitine palmitoyltransferase (CPT) I to malonyl-CoA inhibition is high, as suggested by the very low concentration of malonyl-CoA required for 50% inhibition of CPT I (IC50). The rates of oleate oxidation and ketogenesis are respectively 70 and 80% lower in mitochondria isolated from newborn-pig liver than from starved-adult-rat liver mitochondria. Using polarographic measurements, we showed that the oxidation of oleoyl-CoA and palmitoyl-L-carnitine is very low when the acetyl-CoA produced is channelled into the hydroxymethylglutaryl-CoA (HMG-CoA) pathway by addition of malonate. In contrast, the oxidation of the same substrates is high when the acetyl-CoA produced is directed towards the citric acid cycle by addition of malate. We demonstrate that the limitation of ketogenesis in newborn-pig liver is due to a very low amount and activity of mitochondrial HMG-CoA synthase as compared with rat liver mitochondria, and suggest that this could promote the accumulation of acetyl-CoA and/or beta-oxidation products that in turn would decrease the overall rate of fatty acid oxidation in newborn- and adult-pig livers.

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Adaptations of glucose and fatty acid metabolism during perinatal period and suckling-weaning transition

Cited by 462 publications

References 0 publications

The Mitochondrial Carnitine Palmitoyltransferase System — From Concept to Molecular Analysis

The Mitochondrial Carnitine Palmitoyltransferase System — From Concept to Molecular Analysis

GLUT2, glucose sensing and glucose homeostasis

Hepatic ketogenesis in newborn pigs is limited by low mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity

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