Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat

Jean Z. Lin; Alexandro J. Martagón; Stephanie L. Cimini; Daniel D. Gonzalez; David W. Tinkey; Amadeo Biter; John D. Baxter; Paul Webb; Jan-Ake Gustafsson; Sean M. Hartig; Kevin J. Phillips

doi:10.1016/j.celrep.2015.10.022

Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat

Jean Z. Lin, Alexandro J. Martagón, Stephanie L. Cimini, Daniel D. Gonzalez, David W. Tinkey, Amadeo Biter, John D. Baxter, Paul Webb, Jan-Ake Gustafsson, Sean M. Hartig, Kevin J. Phillips

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91 Scopus citations

Abstract

The functional conversion of white adipose tissue (WAT) into a tissue with brown adipose tissue (BAT)-like activity, often referred to as "browning," represents an intriguing strategy for combating obesity and metabolic disease. We demonstrate that thyroid hormone receptor (TR) activation by a synthetic agonist markedly induces a program of adaptive thermogenesis in subcutaneous WAT that coincides with a restoration of cold tolerance to cold-intolerant mice. Distinct from most other browning agents, pharmacological TR activation dissociates the browning of WAT from activation of classical BAT. TR agonism also induces the browning of white adipocytes in vitro, indicating that TR-mediated browning is cell autonomous. These data establish TR agonists as a class of browning agents, implicate the TRs in the browning of WAT, and suggest a profound pharmacological potential of this action.

Original language	English (US)
Pages (from-to)	1528-1537
Number of pages	10
Journal	Cell Reports
Volume	13
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2015.10.022
State	Published - Nov 24 2015

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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title = "Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat",

abstract = "The functional conversion of white adipose tissue (WAT) into a tissue with brown adipose tissue (BAT)-like activity, often referred to as {"}browning,{"} represents an intriguing strategy for combating obesity and metabolic disease. We demonstrate that thyroid hormone receptor (TR) activation by a synthetic agonist markedly induces a program of adaptive thermogenesis in subcutaneous WAT that coincides with a restoration of cold tolerance to cold-intolerant mice. Distinct from most other browning agents, pharmacological TR activation dissociates the browning of WAT from activation of classical BAT. TR agonism also induces the browning of white adipocytes in vitro, indicating that TR-mediated browning is cell autonomous. These data establish TR agonists as a class of browning agents, implicate the TRs in the browning of WAT, and suggest a profound pharmacological potential of this action.",

author = "Lin, {Jean Z.} and Martag{\'o}n, {Alexandro J.} and Cimini, {Stephanie L.} and Gonzalez, {Daniel D.} and Tinkey, {David W.} and Amadeo Biter and Baxter, {John D.} and Paul Webb and Jan-Ake Gustafsson and Hartig, {Sean M.} and Phillips, {Kevin J.}",

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doi = "10.1016/j.celrep.2015.10.022",

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T1 - Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat

AU - Lin, Jean Z.

AU - Martagón, Alexandro J.

AU - Cimini, Stephanie L.

AU - Gonzalez, Daniel D.

AU - Tinkey, David W.

AU - Biter, Amadeo

AU - Baxter, John D.

AU - Webb, Paul

AU - Gustafsson, Jan-Ake

AU - Hartig, Sean M.

AU - Phillips, Kevin J.

PY - 2015/11/24

Y1 - 2015/11/24

N2 - The functional conversion of white adipose tissue (WAT) into a tissue with brown adipose tissue (BAT)-like activity, often referred to as "browning," represents an intriguing strategy for combating obesity and metabolic disease. We demonstrate that thyroid hormone receptor (TR) activation by a synthetic agonist markedly induces a program of adaptive thermogenesis in subcutaneous WAT that coincides with a restoration of cold tolerance to cold-intolerant mice. Distinct from most other browning agents, pharmacological TR activation dissociates the browning of WAT from activation of classical BAT. TR agonism also induces the browning of white adipocytes in vitro, indicating that TR-mediated browning is cell autonomous. These data establish TR agonists as a class of browning agents, implicate the TRs in the browning of WAT, and suggest a profound pharmacological potential of this action.

AB - The functional conversion of white adipose tissue (WAT) into a tissue with brown adipose tissue (BAT)-like activity, often referred to as "browning," represents an intriguing strategy for combating obesity and metabolic disease. We demonstrate that thyroid hormone receptor (TR) activation by a synthetic agonist markedly induces a program of adaptive thermogenesis in subcutaneous WAT that coincides with a restoration of cold tolerance to cold-intolerant mice. Distinct from most other browning agents, pharmacological TR activation dissociates the browning of WAT from activation of classical BAT. TR agonism also induces the browning of white adipocytes in vitro, indicating that TR-mediated browning is cell autonomous. These data establish TR agonists as a class of browning agents, implicate the TRs in the browning of WAT, and suggest a profound pharmacological potential of this action.

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JO - Cell Reports

JF - Cell Reports

IS - 8

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Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat

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