3,5-Diiodo-L-Thyronine Exerts Metabolically Favorable Effects on Visceral Adipose Tissue of Rats Receiving a High-Fat Diet

Elena Silvestri, Rosalba Senese, Federica Cioffi, Rita De Matteis, Davide Lattanzi, Assunta Lombardi, Antonia Giacco, Anna Maria Salzano, Andrea Scaloni, Michele Ceccarelli, Maria Moreno, Fernando Goglia, Antonia Lanni, Pieter de Lange

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Abstract

When administered to rats receiving a high-fat diet (HFD), 3,5-diiodo-L-thyronine (3,5-T2) [at a dose of 25 μg/100 g body weight (BW)] is known to increase energy expenditure and to prevent HFD-induced adiposity. Here, we investigated which cellular and molecular processes in visceral white adipose tissue (VAT) contributed to the beneficial effect of 3,5-T2 over time (between 1 day and 4 weeks following administration). 3,5-T2 programmed the adipocyte for lipolysis by rapidly inducing hormone sensitive lipase (HSL) phosphorylation at the protein kinase A-responsive site Ser563, accompanied with glycerol release at the 1-week time-point, contributing to the partial normalization of adipocyte volume with respect to control (N) animals. After two weeks, when the adipocyte volumes of HFD-3,5-T2 rats were completely normalized to those of the controls (N), 3,5-T2 consistently induced HSL phosphorylation at Ser563, indicative of a combined effect of 3,5-T2-induced adipose lipolysis and increasing non-adipose oxidative metabolism. VAT proteome analysis after 4 weeks of treatment revealed that 3,5-T2 significantly altered the proteomic profile of HFD rats and produced a marked pro-angiogenic action. This was associated with a reduced representation of proteins involved in lipid storage or related to response to oxidative stress, and a normalization of the levels of those involved in lipogenesis-associated mitochondrial function. In conclusion, the prevention of VAT mass-gain by 3,5-T2 occurred through different molecular pathways that, together with the previously reported stimulation of resting metabolism and liver fatty acid oxidation, are associated with an anti adipogenic/lipogenic potential and positively impact on tissue health.

Original languageEnglish
JournalNutrients
Volume11
Issue number2
DOIs
Publication statusPublished - 27 Jan 2019
Externally publishedYes

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Keywords

  • 3,5-diiodo-L-thyronine
  • ATGL
  • hormone sensitive lipase
  • lipolysis
  • proteomics
  • visceral white adipose tissue

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

Cite this

Silvestri, E., Senese, R., Cioffi, F., De Matteis, R., Lattanzi, D., Lombardi, A., Giacco, A., Salzano, A. M., Scaloni, A., Ceccarelli, M., Moreno, M., Goglia, F., Lanni, A., & de Lange, P. (2019). 3,5-Diiodo-L-Thyronine Exerts Metabolically Favorable Effects on Visceral Adipose Tissue of Rats Receiving a High-Fat Diet. Nutrients, 11(2). https://doi.org/10.3390/nu11020278