3,5-Diiodo-L-Thyronine increases FoF1-ATP synthase activity and cardiolipin level in liver mitochondria of hypothyroid rats

Cavallo, Alessandro; Gnoni, Antonio; Conte, Elena; Siculella, Luisa; Zanotti, Franco; Papa, Sergio; Gnoni, Gabriele V.

doi:10.1007/s10863-011-9366-3

Cited by 22 publications

(20 citation statements)

References 44 publications

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“…A great body of evidence has reported that T2, previously considered only a T3 catabolite, is able to mimic some of T3’s effects on the metabolism [11]. T2 action appears to be more rapid than that of T3, and seems to be independent of protein synthesis [11,12,13,14,15]. It has been shown that T2 administration to rats increases their resting metabolic rate by modulating mitochondrial function [16,17,18], prevents diet-induced obesity by enhancing burning of fats [19], and reduces liver steatosis in rats fed on a high-fat diet [20].…”

Section: Introductionmentioning

confidence: 99%

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Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms

Damiano

Rochira

Gnoni

et al. 2017

IJMS

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The thyroid hormones (THs) 3,3′,5,5′-tetraiodo-l-thyronine (T4) and 3,5,3′-triiodo-l-thyronine (T3) influence many metabolic pathways. The major physiological function of THs is to sustain basal energy expenditure, by acting primarily on carbohydrate and lipid catabolism. Beyond the mobilization and degradation of lipids, at the hepatic level THs stimulate the de novo fatty acid synthesis (de novo lipogenesis, DNL), through both the modulation of gene expression and the rapid activation of cell signalling pathways. 3,5-Diiodo-l-thyronine (T2), previously considered only a T3 catabolite, has been shown to mimic some of T3 effects on lipid catabolism. However, T2 action is more rapid than that of T3, and seems to be independent of protein synthesis. An inhibitory effect on DNL has been documented for T2. Here, we give an overview of the mechanisms of THs action on liver fatty acid metabolism, focusing on the different effects exerted by T2 and T3 on the regulation of the DNL. The inhibitory action on DNL exerted by T2 makes this compound a potential and attractive drug for the treatment of some metabolic diseases and cancer.

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Section: Introductionmentioning

confidence: 99%

“…It stimulates the mitochondrial oxidative capacity and respiration rate [9,11,14,15,23] and increases FoF1-ATP synthase expression and activity in rat liver mitochondria [14,24]. …”

Section: Introductionmentioning

confidence: 99%

Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms

Damiano

Rochira

Gnoni

et al. 2017

IJMS

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“…It has been demonstrated that iodothyronines other than T 3 and T 4 can play a physiological role. Several evidences indicated that 3,5-diiodo-L-thyronine (T 2 ), previously considered as simple degradation product of T 3 , appears to influence energy metabolism [1], [14], [15]. T 2 is able to stimulate the mitochondrial oxidative capacity and respiration rate in mammals [1], [11], [14], [15].…”

Section: Introductionmentioning

confidence: 99%

“…Animal cells generate most of their ATP by oxidative phosphorylation (OXPHOS), a process located in the inner mitochondrial membrane. We have recently shown that the acute T 2 administration to hypothyroid rats increases F o F 1 -ATP synthase activity in liver mitochondria [15]. T 2 effects on different metabolic pathways have been shown to be more rapid than those of T 3 and often independent of protein synthesis [15]–[19].…”

Section: Introductionmentioning

confidence: 99%

“…Considering that T 2 is able to reduce hepatic lipid accumulation in several high-fat experimental models [21]–[25] and in the light of our recent findings on the stimulating effect of this hormone on F o F 1 -ATP synthase activity in rat liver [15], we decided to investigate the biochemical mechanisms underlying the capacity of T 2 to affect lipid degradation. To this end we studied in rat-liver cells the effect of T 2 on the complete pathway of fatty acid oxidation from CPT-I activity and fatty acid oxidation rate to the downstream pathways such as mitochondrial OXPHOS activities.…”

Section: Introductionmentioning

confidence: 99%

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3,5-Diiodo-L-Thyronine Administration To Hypothyroid Rats Rapidly Enhances Fatty Acid Oxidation Rate and Bioenergetic Parameters in Liver Cells

et al. 2013

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Growing evidence shows that, among triiodothyronine derivatives, 3,5 diiodo-L-thyronine (T2) plays an important role in energy metabolism and fat storage. In the present study, short-term effects of T2 administration to hypothyroid rats on fatty acid oxidation rate and bioenergetic parameters were investigated. Within 1 h following T2 injection, state 3 and state 4 respiration rates, which were reduced in hypothyroid mitochondria, were noticeably increased particularly in succinate- with respect to glutamate/malate-energized mitochondria. Maximal respiratory activity, observed when glutamate/malate/succinate were simultaneously present in the respiratory medium, was significantly stimulated by T2 treatment. A T2-induced increase in respiratory rates was also observed when palmitoyl-CoA or L-palmitoylcarnitine were used as substrates. No significant change in respiratory control index and ADP/O ratio was observed. The activities of the mitochondrial respiratory chain complexes, especially Complex II, were increased in T2-treated rats. In the latter, Complex V activities, assayed in both ATP synthesis and hydrolysis direction, were enhanced. The rate of fatty acid oxidation, followed by conversion of [14C]palmitate to CO2 and ketone bodies, was higher in hepatocytes isolated from T2-treated rats. This increase occurs in parallel with the raise in the activity of carnitine palmitoyltransferase-I, the rate limiting enzyme of fatty acid β-oxidation, assayed in situ in digitonin-permeabilized hepatocytes. Overall, these results indicate that T2 rapidly increases the ability of mitochondria to import and oxidize fatty acids. An emerging idea in the literature is the ability of T2 to reduce adiposity and dyslipidemia and to prevent the development in liver steatosis. The results of the present study, showing a rapid T2-induced increase in the ability of mitochondria to import and oxidize fatty acids, may contribute to understand the biochemical mechanisms of T2-metabolic effects.

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Acute administration of 3,5-diiodo-L-thyronine to hypothyroid rats stimulates bioenergetic parameters in liver mitochondria

Cavallo

Taurino

Damiano

et al. 2016

J Bioenerg Biomembr

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The role of 3,5-diiodo-L-thyronine (T), initially considered only a 3,3',5-triiodo-L-thyronine (T) catabolite, in the bioenergetic metabolism is of growing interest. In this study we investigated the acute effects (within 1 h) of T administration to hypothyroid rats on liver mitochondria fatty acid uptake and β-oxidation rate, mitochondrial efficiency (by measuring proton leak) and mitochondrial oxidative damage (by determining HO release). Fatty acid uptake into mitochondria was measured assaying carnitine palmitoyl transferase (CPT) I and II activities, and fatty acid β-oxidation using palmitoyl-CoA as a respiratory substrate. Mitochondrial fatty acid pattern was defined by gas-liquid chromatography. In hypothyroid + T vs hypothyroid rats we observed a raise in the serum level of nonesterified fatty acids (NEFA), in the mitochondrial CPT system activity and in the fatty acid β-oxidation rate. A parallel increase in the respiratory chain activity, mainly from succinate, occurs. When fatty acids are chelated by bovine serum albumin, a T-induced increase in both state 3 and state 4 respiration is observed, while, when fatty acids are present, mitochondrial uncoupling occurs together with increased proton leak, responsible for mitochondrial thermogenesis. T administration decreases mitochondrial oxidative stress as determined by lower HO production. We conclude that in rat liver mitochondria T acutely enhances the rate of fatty acid β-oxidation, and the activity of the downstream respiratory chain. The T-induced increase in proton leak may contribute to mitochondrial thermogenesis and to the reduction of oxidative stress. Our results strengthen the previously reported ability of T to reduce adiposity, dyslipidemia and to prevent liver steatosis.

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3,5-Diiodo-L-Thyronine increases FoF1-ATP synthase activity and cardiolipin level in liver mitochondria of hypothyroid rats

Cited by 22 publications

References 44 publications

Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms

Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms

3,5-Diiodo-L-Thyronine Administration To Hypothyroid Rats Rapidly Enhances Fatty Acid Oxidation Rate and Bioenergetic Parameters in Liver Cells

Acute administration of 3,5-diiodo-L-thyronine to hypothyroid rats stimulates bioenergetic parameters in liver mitochondria

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