title: Thyroid hormone contributes to the hypolipidemic effect of polyunsaturated fatty acids from fish oil: in vivo evidence for cross talking mechanisms.
abstract: n-3 polyunsaturated fatty acids (n-3 PUFA) from fish oil (FO) exert important lipid-lowering effects, an effect also ascribed to thyroid hormones (TH) and TH receptor β1 (TRβ1)-specific agonists. n-3 PUFA effects are mediated by nuclear receptors, such as peroxisome proliferator-activated receptors (PPAR) and others. In this study, we investigated a role for TH signaling in n-3 PUFA effects. Euthyroid and hypothyroid adult rats (methimazole-treated for 5 weeks) received FO or soybean oil (control) by oral administration for 3 weeks. In euthyroid rats, FO treatment reduced serum triglycerides and cholesterol, diminished body fat, and increased protein content of the animals. In addition, FO-treated rats exhibited higher liver expression of TRβ1 and mitochondrial α-glycerophosphate dehydrogenase (mGPD), at protein and mRNA levels, but no alteration of glutathione S-transferase or type 1 deiodinase. In hypothyroid condition, FO induced reduction in serum cholesterol and increase in body protein content, but lost the ability to reduce triglycerides and body fat, and to induce TRβ1 and mGDP expression. FO did not change PPARα liver abundance regardless of thyroid state; however, hypothyroidism led to a marked increase in PPARα liver content but did not alter TRβ1 or TRα expression. The data suggest that part of the effect of n-3 PUFA from FO on lipid metabolism is dependent on TH signaling in specific steps and together with the marked upregulation of PPARα in liver of hypothyroid rats suggest important in vivo consequences of the cross-talking between those fatty acids and TH pathways in liver metabolism.
authors.affiliation: Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Avenida Carlos Chagas Filho, 373, Bloco G, Cidade Universitária - Ilha do Fundão, Rio de Janeiro - RJ 21941-902, Brazil.
authors.forename: Luana Lopes
authors.initials: LL
authors.lastname: Souza
authors.forename: Aline
authors.initials: A
authors.lastname: Cordeiro
authors.forename: Lorraine Soares
authors.initials: LS
authors.lastname: Oliveira
authors.forename: Gabriela Silva Monteiro
authors.initials: GS
authors.lastname: de Paula
authors.forename: Larissa Costa
authors.initials: LC
authors.lastname: Faustino
authors.forename: Tania Maria
authors.initials: TM
authors.lastname: Ortiga-Carvalho
authors.forename: Karen Jesus
authors.initials: KJ
authors.lastname: Oliveira
authors.forename: Carmen Cabanelas
authors.initials: CC
authors.lastname: Pazos-Moura
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002784:Cholesterol / Q000097:blood; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology*; D005994:Glycerophosphates / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D047493:PPAR alpha / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism; D013963:Thyroid Hormones / Q000502:physiology*; D014280:Triglycerides / Q000097:blood
chemical_list: D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D005994:Glycerophosphates; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D014280:Triglycerides; D002784:Cholesterol; C029620:alpha-glycerophosphoric acid