First Author | Gonzalez-Hurtado E | Year | 2018 |
Journal | Mol Metab | Volume | 7 |
Pages | 45-56 | PubMed ID | 29175051 |
Mgi Jnum | J:262457 | Mgi Id | MGI:6161978 |
Doi | 10.1016/j.molmet.2017.11.004 | Citation | Gonzalez-Hurtado E, et al. (2018) Fatty acid oxidation is required for active and quiescent brown adipose tissue maintenance and thermogenic programing. Mol Metab 7:45-56 |
abstractText | 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 (Cpt2(A-/-)), that lack mitochondrial long chain fatty acid beta-oxidation, were subjected to environmental and pharmacologic interventions known to promote thermogenic programming in adipose tissue. RESULTS: Chronic administration of beta3-adrenergic (CL-316243) or thyroid hormone (GC-1) agonists induced a loss of BAT morphology and UCP1 expression in Cpt2(A-/-) 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 degrees C) stimulation induced UCP1 and thermogenic programming in both control and Cpt2(A-/-) adipose tissue albeit to a lesser extent in Cpt2(A-/-) mice. However, thermoneutral housing also induced the loss of UCP1 and BAT morphology in Cpt2(A-/-) 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, Cpt2(A-/-) BAT exhibited increased macrophage infiltration, inflammation and fibrosis irrespective of BAT activation. Finally, obese Cpt2(A-/-) mice housed at thermoneutrality exhibited a loss of interscapular BAT and were refractory to beta3-adrenergic-induced energy expenditure and weight loss. CONCLUSION: Mitochondrial long chain fatty acid beta-oxidation is critical for the maintenance of the brown adipocyte phenotype both during times of activation and quiescence. |