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 journalArticlepeer-review

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)
Pages (from-to)45-56
Number of pages12
JournalMolecular Metabolism
Volume7
DOIs
StatePublished - Jan 2018

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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