TY  - JOUR
A1  - Fischer, Caroline
A1  - Wilken-Schmitz, Annett
A1  - Hernandez-Olmos, Victor
A1  - Proschak, Ewgenij
A1  - Stark, Holger
A1  - Fleming, Ingrid
A1  - Weigert, Andreas
A1  - Thurn, Manuela
A1  - Hofmann, Martine
A1  - Werner, Ernst R.
A1  - Geisslinger, Gerd
A1  - Niederberger, Ellen
A1  - Watschinger, Katrin
A1  - Tegeder, Irmgard
T1  - AGMO inhibitor reduces 3T3-L1 adipogenesis
T2  - Cells
N2  - Alkylglycerol monooxygenase (AGMO) is a tetrahydrobiopterin (BH4)-dependent enzyme with major expression in the liver and white adipose tissue that cleaves alkyl ether glycerolipids. The present study describes the disclosure and biological characterization of a candidate compound (Cp6), which inhibits AGMO with an IC50 of 30–100 µM and 5–20-fold preference of AGMO relative to other BH4-dependent enzymes, i.e., phenylalanine-hydroxylase and nitric oxide synthase. The viability and metabolic activity of mouse 3T3-L1 fibroblasts, HepG2 human hepatocytes and mouse RAW264.7 macrophages were not affected up to 10-fold of the IC50. However, Cp6 reversibly inhibited the differentiation of 3T3-L1 cells towards adipocytes, in which AGMO expression was upregulated upon differentiation. Cp6 reduced the accumulation of lipid droplets in adipocytes upon differentiation and in HepG2 cells exposed to free fatty acids. Cp6 also inhibited IL-4-driven differentiation of RAW264.7 macrophages towards M2-like macrophages, which serve as adipocyte progenitors in adipose tissue. Collectively, the data suggest that pharmacologic AGMO inhibition may affect lipid storage.
KW  - AGMO
KW  - compound screen
KW  - enzyme activity assay
KW  - tetrahydrobiopterin
KW  - 3T3-L1 mouse fibroblasts
KW  - adipocytes
KW  - macrophage polarization
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62119
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-621191
SN  - 2073-4409
VL  - 10
IS  - 5, art. 1081
SP  - 1
EP  - 20
PB  - MDPI
CY  - Basel
ER  -