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

Omar Abdul-Rahman, Endre Kristóf, Quang Minh Doan-Xuan, András Vida, Lilla Nagy, Ambrus Horváth, József Simon, Tamás Maros, István Szentkirályi, Lehel Palotás, Tamás Debreceni, Péter Csizmadia, Tamás Szerafin, Tamás Fodor, Magdolna Szántó, Attila Tóth, Borbála Kiss, Z. Bacsó, P. Bai

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article numbere0157644
JournalPLoS One
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

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White Adipocytes
White Adipose Tissue
white adipose tissue
AMP-Activated Protein Kinases
Stem cells
adipocytes
stem cells
phosphotransferases (kinases)
Stem Cells
Chemical activation
Tissue
Phenotype
phenotype
Organelle Biogenesis
Mesenchymal Stromal Cells
Epinephrine
Peroxisome Proliferator-Activated Receptors
AICA ribonucleotide
Adrenergic Agents
epinephrine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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. / Abdul-Rahman, Omar; Kristóf, Endre; Doan-Xuan, Quang Minh; Vida, András; Nagy, Lilla; Horváth, Ambrus; Simon, József; Maros, Tamás; Szentkirályi, István; Palotás, Lehel; Debreceni, Tamás; Csizmadia, Péter; Szerafin, Tamás; Fodor, Tamás; Szántó, Magdolna; Tóth, Attila; Kiss, Borbála; Bacsó, Z.; Bai, P.

In: PLoS One, Vol. 11, No. 6, e0157644, 01.06.2016.

Research output: Contribution to journalArticle

Abdul-Rahman, O, Kristóf, E, Doan-Xuan, QM, Vida, A, Nagy, L, Horváth, A, Simon, J, Maros, T, Szentkirályi, I, Palotás, L, Debreceni, T, Csizmadia, P, Szerafin, T, Fodor, T, Szántó, M, Tóth, A, Kiss, B, Bacsó, Z & Bai, P 2016, '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', PLoS One, vol. 11, no. 6, e0157644. https://doi.org/10.1371/journal.pone.0157644
Abdul-Rahman, Omar ; Kristóf, Endre ; Doan-Xuan, Quang Minh ; Vida, András ; Nagy, Lilla ; Horváth, Ambrus ; Simon, József ; Maros, Tamás ; Szentkirályi, István ; Palotás, Lehel ; Debreceni, Tamás ; Csizmadia, Péter ; Szerafin, Tamás ; Fodor, Tamás ; Szántó, Magdolna ; Tóth, Attila ; Kiss, Borbála ; Bacsó, Z. ; Bai, P. / 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. In: PLoS One. 2016 ; Vol. 11, No. 6.
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T1 - 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

AU - Abdul-Rahman, Omar

AU - Kristóf, Endre

AU - Doan-Xuan, Quang Minh

AU - Vida, András

AU - Nagy, Lilla

AU - Horváth, Ambrus

AU - Simon, József

AU - Maros, Tamás

AU - Szentkirályi, István

AU - Palotás, Lehel

AU - Debreceni, Tamás

AU - Csizmadia, Péter

AU - Szerafin, Tamás

AU - Fodor, Tamás

AU - Szántó, Magdolna

AU - Tóth, Attila

AU - Kiss, Borbála

AU - Bacsó, Z.

AU - Bai, P.

PY - 2016/6/1

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N2 - 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.

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