Interaction of diiodothyronines with isolated cytochrome<i>c</i> oxidase

Goglia, Fernando; Lanni, Antonia; Barth, Jörg; Kadenbach, Bernhard

doi:10.1016/0014-5793(94)00476-5

Cited by 63 publications

(19 citation statements)

References 29 publications

(30 reference statements)

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“…To our knowledge, these data represent the first report of the uncoupling effect of T 2 and T 3 in whole hepatocytes in the presence of adequate fuel and O 2 that confirm previous reports, demonstrating the uncoupling effects of THs on isolated mitochondria (Goglia et al 1999). The short-term effects of T 3 , and particularly of T 2 , on mitochondrial respiration could be due to allosteric interaction with cytochrome c oxidase (COX) Va subunit, as shown in isolated rat liver mitochondria (Goglia et al 1994, Arnold et al 1998. The Kadenback group showed that in mitochondria, intrinsic and extrinsic uncoupling mechanisms of oxidative phosphorylation may take place through COX (Ramzan et al 2010).…”

Section: Discussionsupporting

confidence: 86%

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

Grasselli

Voci

Canesi

et al. 2011

Journal of Endocrinology

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Iodothyronines influence lipid metabolism and energy homeostasis. Previous studies demonstrated that 3,5-L-diiodothyronine (T 2 ), as well as 3,3 0 ,5-L-triiodothyronine (T 3 ), was able to both prevent and reverse hepatic steatosis in rats fed a high-fat diet, and this effect depends on a direct action of iodothyronines on the hepatocyte. However, the involvement of thyroid hormone receptors (TRs) in mediating the lipid-lowering effect of iodothyronines was not elucidated. In this study, we investigated the ability of T 2 and T 3 to reduce the lipid overloading using the rat hepatoma FaO cells defective for functional TRs. The absence of constitutive mRNA expression of both TRa1 and TRb1 in FaO cells was verified by RT-qPCR. To mimic the fatty liver condition, FaO cells were treated with a fatty acid mixture and then exposed to pharmacological doses of T 2 or T 3 for 24 h. Lipid accumulation, mRNA expression of the peroxisome proliferator-activated receptors (PPAR-a, -g, -d) the acyl-CoA oxidase (AOX), and the stearoyl CoA desaturase (SCD1), as well as fuel-stimulated O 2 consumption in intact cells, were evaluated. Lipid accumulation was associated with an increase in triacylglycerol content, PPARg mRNA expression, and a decrease in PPARd and SCD1 mRNA expression. The addition of T 2 or T 3 to lipid-overloaded cells resulted in i) reduction in lipid content; ii) downregulation of PPARa, PPARg, and AOX expression; iii) increase in PPARd expression; and iv) stimulation of mitochondrial uncoupling. These data demonstrate, for the first time, that in the hepatocyte, the lipid-lowering actions of both T 2 and T 3 are not mediated by TRs.

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Section: Discussionsupporting

confidence: 86%

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

Grasselli

Voci

Canesi

et al. 2011

Journal of Endocrinology

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“…These data indicate a possible direct interaction of T2 with some components of the respiratory chain. Indeed, this hypothesis was in agreement with previous results showing a direct stimulation of the enzyme cytochrome oxidase (COX) activity isolated from bovine heart (Goglia et al, 1994 ). Arnold and Kadenbach ( 1997 ) showed that (in addition to the mitochondrial membrane potential, the substrate pressure in the respiratory chain and the oxygen concentration) the respiration of animal cells is also controlled by the matrix ATP/ADP ratio, via an interaction of nucleotides with COX.…”

Section: 5-diiodo-l-thyronine (T 2 )supporting

confidence: 92%

The effects of 3,5-diiodothyronine on energy balance

Goglia

2015

Front. Physiol.

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“…The effect of T2 on COX activity, at least in part, would seem to be independent of sympathetic activation and directed at mitochondrial level, since it was observed not only following in vivo administration of T2, but also following its in vitro addition to BAT homogenates obtained from Hypo rats. These data are in accordance with the ability of T2 to interact directly with the COX complex, thereby promoting its activation [ 45 , 46 ]. Apparently, UCP1 also mediates the effect of T2 on mitochondrial BAT thermogenesis since T2 administration enhanced UCP1 immunopositivity/levels in multilocular cells.…”

Section: Discussionsupporting

confidence: 82%

3,5-Diiodo-L-Thyronine Activates Brown Adipose Tissue Thermogenesis in Hypothyroid Rats

et al. 2015

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3,5-diiodo-l-thyronine (T2), a thyroid hormone derivative, is capable of increasing energy expenditure, as well as preventing high fat diet-induced overweight and related metabolic dysfunction. Most studies to date on T2 have been carried out on liver and skeletal muscle. Considering the role of brown adipose tissue (BAT) in energy and metabolic homeostasis, we explored whether T2 could activate BAT thermogenesis. Using euthyroid, hypothyroid, and T2-treated hypothyroid rats (all maintained at thermoneutrality) in morphological and functional studies, we found that hypothyroidism suppresses the maximal oxidative capacity of BAT and thermogenesis, as revealed by reduced mitochondrial content and respiration, enlarged cells and lipid droplets, and increased number of unilocular cells within the tissue. In vivo administration of T2 to hypothyroid rats activated BAT thermogenesis and increased the sympathetic innervation and vascularization of tissue. Likewise, T2 increased BAT oxidative capacity in vitro when added to BAT homogenates from hypothyroid rats. In vivo administration of T2 to hypothyroid rats enhanced mitochondrial respiration. Moreover, UCP1 seems to be a molecular determinant underlying the effect of T2 on mitochondrial thermogenesis. In fact, inhibition of mitochondrial respiration by GDP and its reactivation by fatty acids were greater in mitochondria from T2-treated hypothyroid rats than untreated hypothyroid rats. In vivo administration of T2 led to an increase in PGC-1α protein levels in nuclei (transient) and mitochondria (longer lasting), suggesting a coordinate effect of T2 in these organelles that ultimately promotes net activation of mitochondrial biogenesis and BAT thermogenesis. The effect of T2 on PGC-1α is similar to that elicited by triiodothyronine. As a whole, the data reported here indicate T2 is a thyroid hormone derivative able to activate BAT thermogenesis.

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Interaction of diiodothyronines with isolated cytochromec oxidase

Cited by 63 publications

References 29 publications

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

The effects of 3,5-diiodothyronine on energy balance

3,5-Diiodo-L-Thyronine Activates Brown Adipose Tissue Thermogenesis in Hypothyroid Rats

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