Alpha-ketoglutarate enhances adipose-derived stem cells survival in wound healing by hypoxia-inducible factor 1-alpha-mediated redox homeostasis and glycogen-dependent bioenergetics

Figure 4 Glycogen storage contributes to survival of adipose-derived stem cells treated with α-ketoglutarate via energy supply. A: Glycolytic flux of mouse adipose-derived stem cells (ADSCs) and α-ketoglutarate-ADSCs (αKG-ADSCs); B: Glucose oxidation rate; C: Palmitate β-oxidation; D: Cell viability during normal (5 mmol/L glucose) or glucose-deprived conditions (0.5 mmol/L glucose); E: Intracellular glycogen deposition; F and G: Cellular glycogen content after inhibition of PYGL with 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) (F) or shRNA (PYGL^KD) (G); H and I: Cell viability of ADSCs, αKG-ADSCs, and αKG-ADSCs after inhibition of PYGL with DAB (H) or shRNA (PYGL^KD) (I); J: Energy status (ratio of ATP to AMP levels); K and L: Intracellular reactive oxygen species levels in ADSCs, αKG-ADSCs, and αKG-ADSCs after inhibition of PYGL with DAB (K) or shRNA (PYGL^KD) (L); M and N: Terminal deoxynucleotidyl transferase dUTP nick end labeling immunostaining (M) at day 3 after cell implantation, with quantification of TUNEL+ cells (N). Data are presented with means ± SEM (^aP < 0.05, ^bP < 0.01, NS: Not significant). ADSCs: Adipose-derived stem cells; αKG-ADSCs: Alpha-ketoglutarate adipose-derived stem cells; MFI: Mean fluorescent intensity; TUNEL: Terminal deoxynucleotidyl transferase dUTP nick end labeling.