AMP-Activated Kinase (AMPK) Activation by AICAR in Human White Adipocytes Derived from Pericardial White Adipose Tissue Stem Cells Induces a Partial Beige-Like Phenotype.
Beige adipocytes are special cells situated in the white adipose tissue. Beige adipocytes, lacking thermogenic cues, morphologically look quite similar to regular white adipocytes, but with a markedly different response to adrenalin. White adipocytes respond to adrenergic stimuli by enhancing lipolysis, while in beige adipocytes adrenalin induces mitochondrial biogenesis too. A key step in the differentiation and function of beige adipocytes is the deacetylation of peroxisome proliferator-activated receptor (PPARγ) by SIRT1 and the consequent mitochondrial biogenesis. AMP-activated protein kinase (AMPK) is an upstream activator of SIRT1, therefore we set out to investigate the role of AMPK in beige adipocyte differentiation using human adipose-derived mesenchymal stem cells (hADMSCs) from pericardial adipose tissue. hADMSCs were differentiated to white and beige adipocytes and the differentiation medium of the white adipocytes was supplemented with 100 μM [(2R,3S,4R,5R)-5-(4-Carbamoyl-5-aminoimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate (AICAR), a known activator of AMPK. The activation of AMPK with AICAR led to the appearance of beige-like morphological properties in differentiated white adipocytes. Namely, smaller lipid droplets appeared in AICAR-treated white adipocytes in a similar fashion as in beige cells. Moreover, in AICAR-treated white adipocytes the mitochondrial network was more fused than in white adipocytes; a fused mitochondrial system was characteristic to beige adipocytes. Despite the morphological similarities between AICAR-treated white adipocytes and beige cells, functionally AICAR-treated white adipocytes were similar to white adipocytes. We were unable to detect increases in basal or cAMP-induced oxygen consumption rate (a marker of mitochondrial biogenesis) when comparing control and AICAR-treated white adipocytes. Similarly, markers of beige adipocytes such as TBX1, UCP1, CIDEA, PRDM16 and TMEM26 remained the same when comparing control and AICAR-treated white adipocytes. Our data point out that in human pericardial hADMSCs the role of AMPK activation in controlling beige differentiation is restricted to morphological features, but not to actual metabolic changes.
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.|MTA-DE Cell Biology and Signaling Research Group, Debrecen, H-4032, Hungary.
Omar
O
Abdul-Rahman
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Endre
E
Kristóf
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Quang-Minh
QM
Doan-Xuan
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.|MTA-DE Lendület Laboratory of Cellular Metabolism, Debrecen, H-4032, Hungary.
András
A
Vida
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.|MTA-DE Cell Biology and Signaling Research Group, Debrecen, H-4032, Hungary.
Lilla
L
Nagy
Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Ambrus
A
Horváth
Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
József
J
Simon
Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Tamás
T
Maros
Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
István
I
Szentkirályi
Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Lehel
L
Palotás
Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Tamás
T
Debreceni
Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Péter
P
Csizmadia
Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Tamás
T
Szerafin
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Tamás
T
Fodor
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.|MTA-DE Cell Biology and Signaling Research Group, Debrecen, H-4032, Hungary.
Magdolna
M
Szántó
Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Attila
A
Tóth
Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Borbála
B
Kiss
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Zsolt
Z
Bacsó
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.|MTA-DE Lendület Laboratory of Cellular Metabolism, Debrecen, H-4032, Hungary.|Research Center for Molecular Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Péter
P
Bai
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000069797:Adipocytes, Beige / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D052438:Adipocytes, White / Q000201:enzymology*; D052436:Adipose Tissue, White / Q000166:cytology*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects; D010496:Pericardium / Q000166:cytology*; D010641:Phenotype; D012265:Ribonucleotides / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide