Fatty acid oxidation is required for active and quiescent brown adipose tissue maintenance and thermogenic programing

Elsie Gonzalez-Hurtado, Jieun Lee, Joseph Choi, Michael J Wolfgang

Research output: Contribution to journalArticle

Abstract

Objective: To determine the role of fatty acid oxidation on the cellular, molecular, and physiologic response of brown adipose tissue to disparate paradigms of chronic thermogenic stimulation. Methods: Mice with an adipose-specific loss of Carnitine Palmitoyltransferase 2 (Cpt2A-/-), that lack mitochondrial long chain fatty acid β-oxidation, were subjected to environmental and pharmacologic interventions known to promote thermogenic programming in adipose tissue. Results: Chronic administration of β3-adrenergic (CL-316243) or thyroid hormone (GC-1) agonists induced a loss of BAT morphology and UCP1 expression in Cpt2A-/- mice. Fatty acid oxidation was also required for the browning of white adipose tissue (WAT) and the induction of UCP1 in WAT. In contrast, chronic cold (15 °C) stimulation induced UCP1 and thermogenic programming in both control and Cpt2A-/- adipose tissue albeit to a lesser extent in Cpt2A-/- mice. However, thermoneutral housing also induced the loss of UCP1 and BAT morphology in Cpt2A-/- mice. Therefore, adipose fatty acid oxidation is required for both the acute agonist-induced activation of BAT and the maintenance of quiescent BAT. Consistent with this data, Cpt2A-/- BAT exhibited increased macrophage infiltration, inflammation and fibrosis irrespective of BAT activation. Finally, obese Cpt2A-/- mice housed at thermoneutrality exhibited a loss of interscapular BAT and were refractory to β3-adrenergic-induced energy expenditure and weight loss. Conclusion: Mitochondrial long chain fatty acid β-oxidation is critical for the maintenance of the brown adipocyte phenotype both during times of activation and quiescence.

Original languageEnglish (US)
JournalMolecular Metabolism
DOIs
StateAccepted/In press - Jan 1 2017

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Brown Adipose Tissue
Fatty Acids
Maintenance
White Adipose Tissue
Adrenergic Agents
Adipose Tissue
Brown Adipocytes
Carnitine O-Palmitoyltransferase
Obese Mice
Thyroid Hormones
Energy Metabolism
Weight Loss
Fibrosis
Macrophages
Inflammation
Phenotype

Keywords

  • Adipose macrophage
  • Adrenergic signaling
  • Brown adipose tissue
  • Cold induced thermogenesis
  • Fatty acid oxidation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Fatty acid oxidation is required for active and quiescent brown adipose tissue maintenance and thermogenic programing. / Gonzalez-Hurtado, Elsie; Lee, Jieun; Choi, Joseph; Wolfgang, Michael J.

In: Molecular Metabolism, 01.01.2017.

Research output: Contribution to journalArticle

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