title: 3,5-Diiodo-L-thyronine activates brown adipose tissue thermogenesis in hypothyroid rats.
abstract: 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.
authors: Dipartimento di Biologia, Università degli Studi di Napoli "Federico II", Napoli, Italy.
authors: Assunta
authors: A
authors: Lombardi
authors: Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli, Caserta, Italy.
authors: Rosalba
authors: R
authors: Senese
authors: Dipartimento di Scienze Biomolecolari, Sezione di Scienze Motorie e della Salute Università degli Studi di Urbino "Carlo Bo", Urbino, Italy.
authors: Rita
authors: R
authors: De Matteis
authors: Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Benevento, Italy.
authors: Rosa Anna
authors: RA
authors: Busiello
authors: Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Benevento, Italy.
authors: Federica
authors: F
authors: Cioffi
authors: Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Benevento, Italy.
authors: Fernando
authors: F
authors: Goglia
authors: Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli, Caserta, Italy.
authors: Antonia
authors: A
authors: Lanni
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001837:Body Weights and Measures; D019069:Cell Respiration / Q000187:drug effects; D004104:Diiodothyronines / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D006652:Histological Techniques; D007037:Hypothyroidism / Q000503:physiopathology* / Q000517:prevention & control; D007150:Immunohistochemistry; D008928:Mitochondria / Q000187:drug effects; D051381:Rats; D022722:Thermogenesis / Q000187:drug effects* / Q000502:physiology
chemical_list: D004104:Diiodothyronines; C030103:3,5-diiodothyronine