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.
Highlights
The energy balance of an organism depends on the net of energy intake and energy expenditure
AICAR-induced AMP-activated protein kinase (AMPK) activation leads to beige-like morphological changes in Human adipose-derived mesenchymal stem cells (hADMSCs)-derived white adipocytes
The treatment of white adipocytes with 100 μM AICAR enhanced AMPK activity almost to the same extent as in beige adipocytes (Fig 2) that suggested a role for AMPK in beige adipocyte differentiation and function
Summary
The energy balance of an organism depends on the net of energy intake and energy expenditure. A novel cell type called beige, or brite (blended from brown and white) adipocytes were identified in white adipose tissue (WAT) that seems to play an indispensable role in energy expenditure [7, 8]. It is conceivable that due to the proportions of WAT in the human body, beige adipocytes may have similar importance in energy expenditure comparable to skeletal muscle. Functional beige adipocytes were shown in humans too [7, 12], these cells are transplantable [13]. AMPK activation had been implicated in brown adipocyte differentiation and function [26]. In the present study we set out to assess that possibility
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