Rosiglitazone and a β3-adrenoceptor agonist are both required for functional browning of white adipocytes in culture

Jon Merlin, Masaaki Sato, Ling Yeong Chia, Richard Fahey, Mohsen Pakzad, Cameron J. Nowell, Roger J. Summers, Tore Bengtsson, Bronwyn A. Evans, Dana S. Hutchinson

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

The recruitment of brite (or beige) adipocytes has been advocated as a means to combat obesity, due to their ability to phenotypically resemble brown adipocytes (BA). Lineage studies indicate that brite adipocytes are formed by differentiation of precursor cells or by direct conversion of existing white adipocytes, depending on the adipose depot examined. We have systematically compared the gene expression profile and a functional output (oxygen consumption) in mouse adipocytes cultured from two contrasting depots, namely interscapular brown adipose tissue, and inguinal white adipose tissue (iWAT), following treatment with a known browning agent, the peroxisome proliferator-activated receptor (PPARγ) activator rosiglitazone. Prototypical BA readily express uncoupling protein (UCP)1, and upstream regulators including the β3-adrenoceptor and transcription factors involved in energy homeostasis. Adipocytes from inguinal WAT display maximal UCP1 expression and mitochondrial uncoupling only when treated with a combination of the PPARγ activator rosiglitazone and a β3-adrenoceptor agonist. In conclusion, brite adipocytes are fully activated only when a browning agent (rosiglitazone) and a thermogenic agent (β3-adrenoceptor agonist) are added in combination. The presence of rosiglitazone throughout the 7-day culture period partially masks the effects of β3-adrenoceptor signaling in inguinal white adipocyte cultures, whereas including rosiglitazone only for the first 3 days promotes robust β3-adrenoceptor expression and provides an improved window for detection of β3-adrenoceptor responses.

Original languageEnglish
Article number249
Number of pages17
JournalFrontiers in Endocrinology
Volume9
Issue numberMAY
DOIs
Publication statusPublished - 30 May 2018

Keywords

  • Adipocyte
  • Adrenoceptor
  • Beta adrenergic receptors
  • CL316243
  • Rosiglitazone
  • Seahorse xf96 analysis
  • Uncoupling protein 1

Cite this

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title = "Rosiglitazone and a β3-adrenoceptor agonist are both required for functional browning of white adipocytes in culture",
abstract = "The recruitment of brite (or beige) adipocytes has been advocated as a means to combat obesity, due to their ability to phenotypically resemble brown adipocytes (BA). Lineage studies indicate that brite adipocytes are formed by differentiation of precursor cells or by direct conversion of existing white adipocytes, depending on the adipose depot examined. We have systematically compared the gene expression profile and a functional output (oxygen consumption) in mouse adipocytes cultured from two contrasting depots, namely interscapular brown adipose tissue, and inguinal white adipose tissue (iWAT), following treatment with a known browning agent, the peroxisome proliferator-activated receptor (PPARγ) activator rosiglitazone. Prototypical BA readily express uncoupling protein (UCP)1, and upstream regulators including the β3-adrenoceptor and transcription factors involved in energy homeostasis. Adipocytes from inguinal WAT display maximal UCP1 expression and mitochondrial uncoupling only when treated with a combination of the PPARγ activator rosiglitazone and a β3-adrenoceptor agonist. In conclusion, brite adipocytes are fully activated only when a browning agent (rosiglitazone) and a thermogenic agent (β3-adrenoceptor agonist) are added in combination. The presence of rosiglitazone throughout the 7-day culture period partially masks the effects of β3-adrenoceptor signaling in inguinal white adipocyte cultures, whereas including rosiglitazone only for the first 3 days promotes robust β3-adrenoceptor expression and provides an improved window for detection of β3-adrenoceptor responses.",
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author = "Jon Merlin and Masaaki Sato and Chia, {Ling Yeong} and Richard Fahey and Mohsen Pakzad and Nowell, {Cameron J.} and Summers, {Roger J.} and Tore Bengtsson and Evans, {Bronwyn A.} and Hutchinson, {Dana S.}",
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Rosiglitazone and a β3-adrenoceptor agonist are both required for functional browning of white adipocytes in culture. / Merlin, Jon; Sato, Masaaki; Chia, Ling Yeong; Fahey, Richard; Pakzad, Mohsen; Nowell, Cameron J.; Summers, Roger J.; Bengtsson, Tore; Evans, Bronwyn A.; Hutchinson, Dana S.

In: Frontiers in Endocrinology, Vol. 9, No. MAY, 249, 30.05.2018.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Merlin, Jon

AU - Sato, Masaaki

AU - Chia, Ling Yeong

AU - Fahey, Richard

AU - Pakzad, Mohsen

AU - Nowell, Cameron J.

AU - Summers, Roger J.

AU - Bengtsson, Tore

AU - Evans, Bronwyn A.

AU - Hutchinson, Dana S.

PY - 2018/5/30

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AB - The recruitment of brite (or beige) adipocytes has been advocated as a means to combat obesity, due to their ability to phenotypically resemble brown adipocytes (BA). Lineage studies indicate that brite adipocytes are formed by differentiation of precursor cells or by direct conversion of existing white adipocytes, depending on the adipose depot examined. We have systematically compared the gene expression profile and a functional output (oxygen consumption) in mouse adipocytes cultured from two contrasting depots, namely interscapular brown adipose tissue, and inguinal white adipose tissue (iWAT), following treatment with a known browning agent, the peroxisome proliferator-activated receptor (PPARγ) activator rosiglitazone. Prototypical BA readily express uncoupling protein (UCP)1, and upstream regulators including the β3-adrenoceptor and transcription factors involved in energy homeostasis. Adipocytes from inguinal WAT display maximal UCP1 expression and mitochondrial uncoupling only when treated with a combination of the PPARγ activator rosiglitazone and a β3-adrenoceptor agonist. In conclusion, brite adipocytes are fully activated only when a browning agent (rosiglitazone) and a thermogenic agent (β3-adrenoceptor agonist) are added in combination. The presence of rosiglitazone throughout the 7-day culture period partially masks the effects of β3-adrenoceptor signaling in inguinal white adipocyte cultures, whereas including rosiglitazone only for the first 3 days promotes robust β3-adrenoceptor expression and provides an improved window for detection of β3-adrenoceptor responses.

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KW - Adrenoceptor

KW - Beta adrenergic receptors

KW - CL316243

KW - Rosiglitazone

KW - Seahorse xf96 analysis

KW - Uncoupling protein 1

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