The Effect of 3,5,3′-Triiodothyronine on Phosphoenolpyruvate Carboxykinase, Fatty Acid Synthetase and Malic Enzyme Activity of Liver and Brown Fat of Fetal and Neonatal Rats

Hahn, Peter; Hassanali, Salim

doi:10.1159/000241509

Cited by 15 publications

(6 citation statements)

References 13 publications

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“…Additionally, studies performed in suckling rats injected with T 3 , during 2 d, reported no changes in the activity of the liver FAS (35). We observed in the liver of the pups a decrease in FAS activity at day 7 and of ACC activity at day 14 of lactation.…”

Section: Table 2 Effects Of Hyperthyroidism On Liver Triglyceride Andsupporting

confidence: 45%

Hyperthyroidism affects lipid metabolism in lactating and suckling rats

Varas

Jahn

Giménez

2001

Lipids

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Two per thousand pregnant women have hyperthyroidism (HT), and although the symptoms are attenuated during pregnancy, they rebound after delivery, affecting infant development. To examine the effects of hyperthyroidism on lactation, we studied lipid metabolism in maternal mammary glands and livers of hyperthyroid rats and their pups. Thyroxine (10 microg/100 g body weight/d) or vehicle-treated rats were made pregnant 2 wk after commencement of treatment and sacrificed on days 7, 14, and 21 of lactation with the litters. Circulating triiodothyronine and tetraiodothyronine concentrations in the HT mothers were increased on all days. Hepatic esterified cholesterol (EC) and free cholesterol (FC) and triglyceride (TG) concentrations were diminished on days 14 and 21. Lipid synthesis, measured by incorporation of [3H]H2O into EC, FC, and TG, fatty acid synthase, and acetyl CoA carboxylase activities increased at day 14, while incorporation into FC and EC decreased at days 7 and 21, respectively. Mammary FC and TG concentrations were diminished at day 14; incorporation of [3H]H2O into TG decreased at days 7 and 21, and incorporation of [3H]H2O into FC increased at day 14. In the HT pups, growth rate was diminished, tetraiodothyronine concentration rose at days 7 and 14 of lactation, and triiodothyronine increased only at day 14. Liver TG concentrations increased at day 7 and fell at day 14, while FC increased at day 14 and only acetyl CoA carboxylase activity fell at day 14. Thus, hyperthyroidism changed maternal liver and mammary lipid metabolism, with decreased lipid concentration in spite of increased liver rate of synthesis and decreases in mammary synthesis. These changes, along with the mild hyperthyroidism of the litters, may have contributed to their reduced growth rate.

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Section: Table 2 Effects Of Hyperthyroidism On Liver Triglyceride Andsupporting

confidence: 45%

Hyperthyroidism affects lipid metabolism in lactating and suckling rats

Varas

Jahn

Giménez

2001

Lipids

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“…This suggests that T 3 rather than T 4 is the primary thyroid hormone involved in the developmental control of tissue gluconeogenic enzyme activity in utero . Indeed, previous studies have shown that raising the plasma T 3 concentration in fetal rats by maternal T 3 treatment close to term causes a significant increase in hepatic PEPCK activity (Hahn & Hassanali, 1982). Furthermore, direct intraperitoneal administration of thyroid hormones to the rat fetus accelerates the normal maturational increase in hepatic G6P activity (Greengard, 1969).…”

Section: Discussionmentioning

confidence: 99%

Developmental regulation of hepatic and renal gluconeogenic enzymes by thyroid hormones in fetal sheep during late gestation

Forhead¹,

Poore²,

Mapstone³

et al. 2003

J Physiology

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Tissue glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) activities were investigated in sheep fetuses after experimental manipulation of thyroid hormone status. Increments in hepatic and renal G6P and PEPCK activities seen between 127-130 and 140-145 days of gestation (term, 145 ± 2 days) were abolished when the normal prepartum rise in plasma triiodothyronine (T 3 ), but not cortisol, was prevented by fetal thyroidectomy (TX). At 127-130 days, hepatic and renal G6P, and renal PEPCK, activities were similar in intact and TX fetuses; however, hepatic PEPCK was increased by TX. At 140-145 days, tissue G6P and PEPCK activities in TX fetuses were lower than in intact fetuses. In immature fetuses infused with cortisol (2-3 mg (kg body wt) _1 day _1 ) for five days, hepatic and renal enzyme activities were increased to those seen in mature fetuses near term. After five days of T 3 infusion (8-12 mg (kg body wt) _1 day _1 ), G6P and PEPCK activities in the liver and kidney were greater than in saline-infused fetuses, but only renal G6P and PEPCK increased to the level seen close to term. Therefore, in fetal sheep, thyroid hormones are important for the prepartum rises in G6P and PEPCK activities in the liver and kidney and may mediate, in part, the maturational effects of cortisol.

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“…Hepatic gluconeogenesis does not become active until shortly after birth (Schaub et al, 1972) and increases substantially and rapidly to levels above those in the adult liver (Beaudry et al, 1977). The high insulin‐to‐glucagon ratio in utero is quickly and substantially reversed in the early neonate (Fernández‐Milán et al, 2013; Girard, 1990; Hahn & Hassanali, 1982; Ktorza et al, 1985; Lyonnet et al, 1988). A reduced counterregulatory influence of insulin on hepatic glucose handling, potentially affecting either glucagon‐activated pathway, is an important hormonal component of the adaptive response in the neonate (Girard, 1990; Hahn & Hassanali, 1982; Mlekusch et al, 1981; Nurjhan et al, 1985).…”

Section: Role Of the Ac/camp Pathway In Meeting Elevated Glucose Dema...mentioning

confidence: 99%

“…The high insulin‐to‐glucagon ratio in utero is quickly and substantially reversed in the early neonate (Fernández‐Milán et al, 2013; Girard, 1990; Hahn & Hassanali, 1982; Ktorza et al, 1985; Lyonnet et al, 1988). A reduced counterregulatory influence of insulin on hepatic glucose handling, potentially affecting either glucagon‐activated pathway, is an important hormonal component of the adaptive response in the neonate (Girard, 1990; Hahn & Hassanali, 1982; Mlekusch et al, 1981; Nurjhan et al, 1985). A rise in plasma corticosteroid levels contributes to the enhancement of gluconeogenic gene expression (Ogias et al, 2010).…”

Section: Role Of the Ac/camp Pathway In Meeting Elevated Glucose Dema...mentioning

confidence: 99%

Glucagon, cyclic AMP, and hepatic glucose mobilization: A half‐century of uncertainty

Rodgers

2022

Physiological Reports

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For at least 50 years, the prevailing view has been that the adenylate cyclase (AC)/cyclic AMP (cAMP)/protein kinase A pathway is the predominant signal mediating the hepatic glucose‐mobilizing actions of glucagon. A wealth of evidence, however, supports the alternative, that the operative signal most of the time is the phospholipase C (PLC)/inositol‐phosphate (IP3)/calcium/calmodulin pathway. The evidence can be summarized as follows: (1) The consensus threshold glucagon concentration for activating AC ex vivo is 100 pM, but the statistical hepatic portal plasma glucagon concentration range, measured by RIA, is between 28 and 60 pM; (2) Within that physiological concentration range, glucagon stimulates the PLC/IP3 pathway and robustly increases glucose output without affecting the AC/cAMP pathway; (3) Activation of a latent, amplified AC/cAMP pathway at concentrations below 60 pM is very unlikely; and (4) Activation of the PLC/IP3 pathway at physiological concentrations produces intracellular effects that are similar to those produced by activation of the AC/cAMP pathway at concentrations above 100 pM, including elevated intracellular calcium and altered activities and expressions of key enzymes involved in glycogenolysis, gluconeogenesis, and glycogen synthesis. Under metabolically stressful conditions, as in the early neonate or exercising adult, plasma glucagon concentrations often exceed 100 pM, recruiting the AC/cAMP pathway and enhancing the activation of PLC/IP3 pathway to boost glucose output, adaptively meeting the elevated systemic glucose demand. Whether the AC/cAMP pathway is consistently activated in starvation or diabetes is not clear. Because the importance of glucagon in the pathogenesis of diabetes is becoming increasingly evident, it is even more urgent now to resolve lingering uncertainties and definitively establish glucagon’s true mechanism of glycemia regulation in health and disease.

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The Effect of 3,5,3′-Triiodothyronine on Phosphoenolpyruvate Carboxykinase, Fatty Acid Synthetase and Malic Enzyme Activity of Liver and Brown Fat of Fetal and Neonatal Rats

Cited by 15 publications

References 13 publications

Hyperthyroidism affects lipid metabolism in lactating and suckling rats

Hyperthyroidism affects lipid metabolism in lactating and suckling rats

Developmental regulation of hepatic and renal gluconeogenic enzymes by thyroid hormones in fetal sheep during late gestation

Glucagon, cyclic AMP, and hepatic glucose mobilization: A half‐century of uncertainty

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