TY  - JOUR
A1  - Kemmerer, Marina
A1  - Finkernagel, Florian
A1  - Frota Cavalcante, Marcela
A1  - Saes Parra Abdalla, Dulcineia
A1  - Müller, Rolf
A1  - Brüne, Bernhard
A1  - Namgaladze, Dmitry
T1  - AMP-activated protein kinase interacts with the peroxisome proliferator-activated receptor delta to induce genes affecting fatty acid oxidation in human macrophages
T2  - PLoS One
N2  - AMP-activated protein kinase (AMPK) maintains energy homeostasis by suppressing cellular ATP-consuming processes and activating catabolic, ATP-producing pathways such as fatty acid oxidation (FAO). The transcription factor peroxisome proliferator-activated receptor δ (PPARδ) also affects fatty acid metabolism, stimulating the expression of genes involved in FAO. To question the interplay of AMPK and PPARδ in human macrophages we transduced primary human macrophages with lentiviral particles encoding for the constitutively active AMPKα1 catalytic subunit, followed by microarray expression analysis after treatment with the PPARδ agonist GW501516. Microarray analysis showed that co-activation of AMPK and PPARδ increased expression of FAO genes, which were validated by quantitative PCR. Induction of these FAO-associated genes was also observed upon infecting macrophages with an adenovirus coding for AMPKγ1 regulatory subunit carrying an activating R70Q mutation. The pharmacological AMPK activator A-769662 increased expression of several FAO genes in a PPARδ- and AMPK-dependent manner. Although GW501516 significantly increased FAO and reduced the triglyceride amount in very low density lipoproteins (VLDL)-loaded foam cells, AMPK activation failed to potentiate this effect, suggesting that increased expression of fatty acid catabolic genes alone may be not sufficient to prevent macrophage lipid overload.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/38004
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-380048
SN  - 1932-6203
N1  - Copyright: © 2015 Kemmerer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
VL  - 10
IS  - (6): e0130893
SP  - 1
EP  - 18
PB  - PLoS
CY  - Lawrence, Kan.
ER  -