RT Journal Article
T1 Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance
A1 Álvarez-Crespo, Mayte
A1 Csikasz, Robert  I.
A1 Martínez Sánchez, Noelia
A1 Diéguez, Carlos
A1 Cannon, Barbara
A1 Nedergaard, Jan
A1 López Pérez, Miguel A.
K1 AMPK
K1 Brown adipose tissue
K1 Hypothalamus
K1 Thyroid hormones
K1 UCP1
AB ObjectiveClassically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice.MethodsWildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry.ResultsWe found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK) and elevated body temperature (0.7 °C). UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning”) of inguinal white adipose tissue (iWAT).ConclusionsWe conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents
PB Elsevier
YR 2016
FD 2016-02-10
LK http://hdl.handle.net/10347/15928
UL http://hdl.handle.net/10347/15928
LA eng
NO This study was supported by grants from the Swedish Research Council and Knut and Alice Wallenbergs Foundation, as well as by funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 281854 – the ObERStress European Research Council project (281854) (ML) Xunta de Galicia (ML: 2015-CP079, Instituto de Salud Carlos III (ISCIII) (ML: PI12/01814), MINECO co-funded by the FEDER Program of EU; CD: BFU2014-55871-P), CIBER de Fisiopatología de la Obesidad y Nutrición (an initiative of ISCIII). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
DS Minerva
RD 24 abr 2026