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

Autor: József Simon, Attila Tóth, Magdolna Szántó, István Szentkirályi, Tamás Debreceni, Ambrus Horvath, Zsolt Bacsó, Borbála Kiss, Omar Abdul-Rahman, Péter Csizmadia, Péter Bai, Tamás Maros, Endre Kristóf, Tamás Szerafin, Lehel Palotás, Tamás Fodor, András Vida, Quang-Minh Doan-Xuan, Lilla Nikoletta Nagy
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Physiology
Adipocytes
White
Adipose tissue
lcsh:Medicine
White adipose tissue
AMP-Activated Protein Kinases
Mitochondrial Dynamics
Biochemistry
Animal Cells
Lipid droplet
Adipocytes
Medicine and Health Sciences
Elméleti orvostudományok
Adipocytes
Beige
lcsh:Science
Energy-Producing Organelles
Connective Tissue Cells
PRDM16
Multidisciplinary
Stem Cells
Respiration
Cell Differentiation
Orvostudományok
Mitochondria
Phenotype
Adipose Tissue
Connective Tissue
Adipogenesis
Cellular Types
Anatomy
Cellular Structures and Organelles
Pericardium
Research Article
medicine.medical_specialty
Adipose Tissue
White
Bioenergetics
Biology
Biosynthesis
03 medical and health sciences
Oxygen Consumption
Internal medicine
Adipocyte Differentiation
medicine
Humans
Cell Shape
Mesenchymal stem cell
lcsh:R
Biology and Life Sciences
AMPK
Cell Biology
Ribonucleotides
Aminoimidazole Carboxamide
Enzyme Activation
Biological Tissue
030104 developmental biology
Endocrinology
Mitochondrial biogenesis
lcsh:Q
Physiological Processes
Developmental Biology
Zdroj: PLoS ONE, Vol 11, Iss 6, p e0157644 (2016)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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