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

Mol Metab. 2018 Jan;7:45-56. doi: 10.1016/j.molmet.2017.11.004. Epub 2017 Nov 11.


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.

Keywords: Adipose macrophage; Adrenergic signaling; Brown adipose tissue; Cold induced thermogenesis; Fatty acid oxidation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Fatty Acids / metabolism*
  • Macrophages / metabolism
  • Male
  • Mice
  • Obesity / metabolism*
  • Oxidation-Reduction
  • Thermogenesis*
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism


  • Fatty Acids
  • UCP1 protein, human
  • Uncoupling Protein 1
  • Carnitine O-Palmitoyltransferase