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Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells.
J Endocrinol. 2011 Jul; 210(1):59-69.JE

Abstract

Iodothyronines influence lipid metabolism and energy homeostasis. Previous studies demonstrated that 3,5-l-diiodothyronine (T(2)), as well as 3,3',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 TRα1 and TRβ1 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-α, -γ, -δ) 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, PPARγ mRNA expression, and a decrease in PPARδ 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 PPARα, PPARγ, and AOX expression; iii) increase in PPARδ 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.

Authors+Show Affiliations

Dipartimento di Biologia, Università di Genova, Corso Europa 26, Genova 16132, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21508094

Citation

Grasselli, Elena, et al. "Non-receptor-mediated Actions Are Responsible for the Lipid-lowering Effects of Iodothyronines in FaO Rat Hepatoma Cells." The Journal of Endocrinology, vol. 210, no. 1, 2011, pp. 59-69.
Grasselli E, Voci A, Canesi L, et al. Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells. J Endocrinol. 2011;210(1):59-69.
Grasselli, E., Voci, A., Canesi, L., Goglia, F., Ravera, S., Panfoli, I., Gallo, G., & Vergani, L. (2011). Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells. The Journal of Endocrinology, 210(1), 59-69. https://doi.org/10.1530/JOE-11-0074
Grasselli E, et al. Non-receptor-mediated Actions Are Responsible for the Lipid-lowering Effects of Iodothyronines in FaO Rat Hepatoma Cells. J Endocrinol. 2011;210(1):59-69. PubMed PMID: 21508094.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells. AU - Grasselli,Elena, AU - Voci,Adriana, AU - Canesi,Laura, AU - Goglia,Fernando, AU - Ravera,Silvia, AU - Panfoli,Isabella, AU - Gallo,Gabriella, AU - Vergani,Laura, Y1 - 2011/04/20/ PY - 2011/4/22/entrez PY - 2011/4/22/pubmed PY - 2011/8/24/medline SP - 59 EP - 69 JF - The Journal of endocrinology JO - J Endocrinol VL - 210 IS - 1 N2 - Iodothyronines influence lipid metabolism and energy homeostasis. Previous studies demonstrated that 3,5-l-diiodothyronine (T(2)), as well as 3,3',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 TRα1 and TRβ1 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-α, -γ, -δ) 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, PPARγ mRNA expression, and a decrease in PPARδ 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 PPARα, PPARγ, and AOX expression; iii) increase in PPARδ 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. SN - 1479-6805 UR - https://www.unboundmedicine.com/medline/citation/21508094/Non_receptor_mediated_actions_are_responsible_for_the_lipid_lowering_effects_of_iodothyronines_in_FaO_rat_hepatoma_cells_ L2 - https://joe.bioscientifica.com/doi/10.1530/JOE-11-0074 DB - PRIME DP - Unbound Medicine ER -