Effect of thyroid state on ketogenic capacity of the isolated perfused liver of starved rats

Müller, Manfred J.; Köster, Helmut; Seitz, Hans

doi:10.1016/0005-2760(81)90309-x

Cited by 25 publications

(15 citation statements)

References 30 publications

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“…It is clear that in isolated perfused livers from hyperthyroid rats, FFA is diverted preferentially away from esterification into oxidative pathways (13, 15-17, 19, 23, 25, 27, 33). Increased production of one or both products of /3-oxidation of fatty acids (CO 2 and the ketone bodies, /8-hydroxybutyrate and acetoacetate) has been reported in the hyperthyroid state (13,16,17,19,23,25,27). In contrast, in the hypothyroid state, decreased (25) or unchanged (13,23) rates of total fatty acid oxidation were reported, with decreased or normal rates of ketogenesis, accompanied invariably by decreased CO 2 production.…”

Section: Fatty Acid Oxidationmentioning

confidence: 89%

“…Increased production of one or both products of /3-oxidation of fatty acids (CO 2 and the ketone bodies, /8-hydroxybutyrate and acetoacetate) has been reported in the hyperthyroid state (13,16,17,19,23,25,27). In contrast, in the hypothyroid state, decreased (25) or unchanged (13,23) rates of total fatty acid oxidation were reported, with decreased or normal rates of ketogenesis, accompanied invariably by decreased CO 2 production. Although there is disagreement about the relative proportions of fatty acid oxidized to CO 2 or ketone bodies by the liver, it is nevertheless clear that total oxidation of FFA is increased in hyper-and decreased in hypothyroid states.…”

Section: Fatty Acid Oxidationmentioning

confidence: 89%

“…The plasma concentration of FFA is elevated in hyperthyroid humans and animals and is diminished in the hypothyroid (9,(13)(14)(15)(16)(17)(18)(19). It is of interest that fasting failed to increase plasma FFA concentrations in hypothyroid patients (20)(21)(22) and animals (23). It is probable that the metabolic demand in hyperthyroidism can be satisfied, in part, by the increased supply of FFA to the liver and other tissues.…”

Section: Fatty Acid Oxidationmentioning

confidence: 96%

“…In our laboratory, hyperthyroidism increased ketogenesis by livers from fed rats without altering the proportion of fatty acid oxidized to 14 CO 2 (25); in the propylthiauracil (PTU)-induced hypothyroid state, the proportion of [l-14 C]oleate converted to 14 CO 2 by the perfused liver was significantly reduced, while ketogenesis was not further reduced. Muller et al (23) observed that the proportion of fatty acid oxidized to ketone bodies by livers from fasted (24 h) rats, perfused with a Ca ++ -free emulsion of Fluorocarbon 43 [Commercial Chemicals Division (3M), St. Paul, MN] in the nonionic detergent Pluronic F68 (BASF Wyandotte, Parsippany, NJ), exceeded that converted to 14 CO 2 for all thyroid states; however, in these studies, 14 CO 2 production and ketogenesis were elevated in livers from hyperthyroid rats and were not different from controls in the hypothyroid state. The studies of Laker and Mayes (13) with perfused livers from fed animals were in agreement with data from our laboratory in that, in the hypothyroid state, the proportion of [l-14 C]oleate converted to 14 CO 2 was similar to that converted to ketone bodies, although in the hyperthyroid state, their data indicated a greater proportion of [l-14 C]oleate was converted to 14 CO 2 than to ketone bodies.…”

Section: Fatty Acid Oxidationmentioning

confidence: 97%

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Plasma Lipoproteins and Regulation of Hepatic Metabolism of Fatty Acids in Altered Thyroid States*

1985

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This article reviews our understanding of effects of thyroid hormone excess and deficiency on hepatic metabolism of FFA, and consequent effects on production, secretion, and metabolism of plasma lipoproteins. In the hyperthyroid state the following alterations are observed. Fatty acid oxidation and ketogenesis are stimulated simultaneously with a paradoxical stimulation of fatty acid synthesis, which may be linked by virtue of a blunted response of mitochondrial carnitine palmitoyltransferase I (CPT-I) to malonyl coenzyme A (CoA). Esterification of fatty acid to triglyceride (TG) is reduced, as is the secretion of the very low density lipoprotein (VLDL) (including VLDL TG, cholesterol, and apoprotein); this may be due, in part, to decreased concentrations of glycerol-3-phosphate (G3P) in the hepatic cell. In the intact animal or patient, however, serum TG concentration is variable, which may reflect increased adipose tissue lipolysis and elevated concentrations of plasma FFA, which would tend to drive VLDL secretion by the liver. Clearance of the VLDL and its metabolic product, the low density lipoprotein (LDL), is increased, resulting in decreased plasma total and LDL cholesterol. Although high density lipoprotein (HDL) cholesterol may also be reduced, the ratio of LDL/HDL cholesterol is further decreased. The regulatory role of the lipoprotein apoproteins is less clear, but hepatic apolipoprotein (apo) B secretion (required for VLDL) is diminished, while apo-AI secretion (required for HDL) is stimulated, perhaps both reflecting rates of synthesis. Plasma concentrations of apo-AI are variable, dependent on relative rates of secretion and clearance. In the hypothyroid, many of these effects are reversed, which results in hyperlipoproteinemias and greater risk for the development of atherosclerotic cardiovascular disease.

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Section: Fatty Acid Oxidationmentioning

confidence: 89%

Section: Fatty Acid Oxidationmentioning

confidence: 89%

Section: Fatty Acid Oxidationmentioning

confidence: 96%

Section: Fatty Acid Oxidationmentioning

confidence: 97%

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Plasma Lipoproteins and Regulation of Hepatic Metabolism of Fatty Acids in Altered Thyroid States*

1985

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“…In accordance with this, we found that hypoT decreased liver ACO mRNA levels but did not modify mitochondrial (CPT-I) fatty acid ␤-oxidation. Because CPT is regulated by the availability of malonyl CoA, the diminished ACC activity may result in a decrease in malonyl CoA that may compensate for the effects of the hypothyroid state, resulting in no overall change in expression, as observed in vitro by Muller, Koster, and Seitz (59).…”

Section: Liver Metabolismmentioning

confidence: 98%

Effects of hypothyroidism on mammary and liver lipid metabolism in virgin and late-pregnant rats

Hapon

Varas

Jahn

et al. 2005

Journal of Lipid Research

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Untreated maternal hypothyroidism (hypoT) has serious consequences in offspring development that may result from the effect on lactation of maternal metabolism dysfunction. We studied the effects of prolonged propylthiouracyl (PTU)-induced hypoT (0.1% PTU in drinking water starting 8 days before mating until day 21 of pregnancy or for 30 days in virgin rats) on liver and mammary lipid metabolism and serum lipid concentrations. In virgins, hypoT reduced hepatic mRNAs associated with triglyceride (TG) and cholesterol synthesis (including fatty acid synthase and 3-hydroxy-3-methylglutaryl coenzyme A reductase), and induced lobuloalveolar mammary development. Thyroid hormones influence all major metabolic pathways. Their most obvious and well-known action is an increase in basal energy expenditure through actions on protein, carbohydrate, and lipid metabolism. With specific regard to liver lipid metabolism, thyroid hormones stimulate fatty acid and cholesterol synthesis (1, 2), increase mobilization of plasma cholesterol and triglycerides (TGs) (3, 4), and stimulate fatty acid and cholesterol degradation (5, 6). Disturbances in thyroid function are commonly associated with alterations in plasma lipid levels. Experimental hypothyroidism (hypoT) induced by propylthiouracyl (PTU) treatment is characterized by the accumulation of plasma LDL cholesterol, and decreased VLDL and plasma TGs (7), generally reflecting reduced binding activity of the hepatic LDL receptor (LDLR), which can be normalized after substitution therapy with thyroid hormone (3,8).Pregnancy is a state of dynamic changes in metabolism and nutrient utilization. The insulin-resistant condition and the increase in plasma estrogen levels occurring during late pregnancy are the main factors responsible for the development of a state of maternal hypertriglyceridemia that has been extensively studied in humans and rats (9)(10)(11). This condition benefits the progeny in two ways. First, it supplies essential fatty acids that are critical to normal fetal development and that circulate primarily esterified and associated with lipoproteins. A linear correlation between maternal and fetal plasma TGs has been described that has an important implication in newborn weight (12, 13). Second, it contributes to milk synthesis in preparation for lactation, providing circulating TG in the form of lipoprotein to the mammary gland (MG) for milk lipid synthesis (9).It has been demonstrated that the induction of hypothyroidism in dairy cows suppresses milk production during the treatment period (14). On the other hand, ad-

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Concerning the decreased D-3-hydroxybutyrate dehydrogenase activity in the liver and heart of hyperthyroid rats

et al. 1990

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Whereas in rat liver mitochondria the hyperthyroid state causes an increase both in fatty acid unsaturation and in the Ea of D-3-hydroxybutyrate dehydrogenase and a decrease in phase transition temperature, in hyperthyroid rat heart mitochondria these changes are negligible. D-3-hydroxybutyrate dehydrogenase in both the liver and the heart mitochondria of hyperthyroid rats is reduced by about 35% [12] but this reduction is not due to changes in membrane fluidity in either tissue. Hypothyroidism, on the other hand, affects BDH activity in neither heart nor liver.

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Effect of thyroid state on ketogenic capacity of the isolated perfused liver of starved rats

Cited by 25 publications

References 30 publications

Plasma Lipoproteins and Regulation of Hepatic Metabolism of Fatty Acids in Altered Thyroid States*

Plasma Lipoproteins and Regulation of Hepatic Metabolism of Fatty Acids in Altered Thyroid States*

Effects of hypothyroidism on mammary and liver lipid metabolism in virgin and late-pregnant rats

Concerning the decreased D-3-hydroxybutyrate dehydrogenase activity in the liver and heart of hyperthyroid rats

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