Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARγ agonist

Natasa Petrovic, Irina G. Shabalina, James A. Timmons, Barbara Cannon, Jan Nedergaard

Research output: Contribution to journalArticle

Abstract

Most physiologically induced examples of recruitment of brown adipose tissue (BAT) occur as a consequence of chronic sympathetic stimulation (norepinephrine release within the tissue). However, in some physiological contexts (e.g., prenatal and prehibernation recruitment), this pathway is functionally contraindicated. Thus a nonsympathetically mediated mechanism of BAT recruitment must exist. Here we have tested whether a PPAR? activation pathway could competently recruit BAT, independently of sympathetic stimulation. We continuously treated primary cultures of mouse brown (pre)adipocytes with the potent peroxisome proliferator-activated receptor-? (PPAR?) agonist rosiglitazone. In rosiglitazone-treated cultures, morphological signs of adipose differentiation and expression levels of the general adipogenic marker aP2 were manifested much earlier than in control cultures. Importantly, in the presence of the PPAR? agonist the brown adipocyte phenotype was significantly enhanced: UCP1 was expressed even in the absence of norepinephrine, and PPARa expression and norepinephrine-induced PGC-1a mRNA levels were significantly increased. However, the augmented levels of PPARa could not explain the brown-fat promoting effect of rosiglitazone, as this effect was still evident in PPARa-null cells. In continuously rosiglitazone-treated brown adipocytes, mitochondriogenesis, an essential part of BAT recruitment, was significantly enhanced. Most importantly, these mitochondria were capable of thermogenesis, as rosiglitazone-treated brown adipocytes responded to the addition of norepinephrine with a large increase in oxygen consumption. This thermogenic response was not observable in rosiglitazone-treated brown adipocytes originating from UCP1-ablated mice; hence, it was UCP1 dependent. Thus the PPAR? pathway represents an alternative, potent, and fully competent mechanism for BAT recruitment, which may be the cellular explanation for the enigmatic recruitment in prehibernation and prenatal states. Copyright © 2008 the American Physiological Society.

Original languageEnglish
Pages (from-to)E287-E296
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume295
Issue number2
DOIs
Publication statusPublished - Aug 2008

Fingerprint

rosiglitazone
Peroxisome Proliferator-Activated Receptors
Brown Adipose Tissue
Brown Adipocytes
Norepinephrine
Null Lymphocytes
Thermogenesis
Oxygen Consumption
Mitochondria

Keywords

  • Brown fat
  • Mitochondria
  • Norepinephrine
  • Peroxisome proliferator-activated receptor-γ
  • Rosiglitazone
  • Thermogenesis

Cite this

Petrovic, Natasa ; Shabalina, Irina G. ; Timmons, James A. ; Cannon, Barbara ; Nedergaard, Jan. / Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARγ agonist. In: American Journal of Physiology - Endocrinology and Metabolism. 2008 ; Vol. 295, No. 2. pp. E287-E296.
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Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARγ agonist. / Petrovic, Natasa; Shabalina, Irina G.; Timmons, James A.; Cannon, Barbara; Nedergaard, Jan.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 295, No. 2, 08.2008, p. E287-E296.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARγ agonist

AU - Petrovic, Natasa

AU - Shabalina, Irina G.

AU - Timmons, James A.

AU - Cannon, Barbara

AU - Nedergaard, Jan

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AB - Most physiologically induced examples of recruitment of brown adipose tissue (BAT) occur as a consequence of chronic sympathetic stimulation (norepinephrine release within the tissue). However, in some physiological contexts (e.g., prenatal and prehibernation recruitment), this pathway is functionally contraindicated. Thus a nonsympathetically mediated mechanism of BAT recruitment must exist. Here we have tested whether a PPAR? activation pathway could competently recruit BAT, independently of sympathetic stimulation. We continuously treated primary cultures of mouse brown (pre)adipocytes with the potent peroxisome proliferator-activated receptor-? (PPAR?) agonist rosiglitazone. In rosiglitazone-treated cultures, morphological signs of adipose differentiation and expression levels of the general adipogenic marker aP2 were manifested much earlier than in control cultures. Importantly, in the presence of the PPAR? agonist the brown adipocyte phenotype was significantly enhanced: UCP1 was expressed even in the absence of norepinephrine, and PPARa expression and norepinephrine-induced PGC-1a mRNA levels were significantly increased. However, the augmented levels of PPARa could not explain the brown-fat promoting effect of rosiglitazone, as this effect was still evident in PPARa-null cells. In continuously rosiglitazone-treated brown adipocytes, mitochondriogenesis, an essential part of BAT recruitment, was significantly enhanced. Most importantly, these mitochondria were capable of thermogenesis, as rosiglitazone-treated brown adipocytes responded to the addition of norepinephrine with a large increase in oxygen consumption. This thermogenic response was not observable in rosiglitazone-treated brown adipocytes originating from UCP1-ablated mice; hence, it was UCP1 dependent. Thus the PPAR? pathway represents an alternative, potent, and fully competent mechanism for BAT recruitment, which may be the cellular explanation for the enigmatic recruitment in prehibernation and prenatal states. Copyright © 2008 the American Physiological Society.

KW - Brown fat

KW - Mitochondria

KW - Norepinephrine

KW - Peroxisome proliferator-activated receptor-γ

KW - Rosiglitazone

KW - Thermogenesis

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M3 - Article

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