LSD۱ in beige adipocytes protects cardiomyocytes against oxygen and glucose deprivation

Objective(s): Epicardial adipose tissue (EpAT) is known for its role in supporting the cardiomyocytes. Lysine-specific demethylase ۱ (LSD۱), a typical lysine demethylase, is an essential regulator for the maintenance of beige adipocytes. However, the effect of LSD۱ in the adipogenic differentiation of beige adipocytes in EpAT, and its function on oxygen and glucose deprivation (OGD)-injured cardiomyocytes remain unclear.Materials and Methods: Heart tissues from young mice and elder mice were collected for immunohistochemical staining. LSD۱ in ۳T۳-L۱ cells was knocked down by LSD۱-shRNA lentivirus infection. The qRT-PCR, western blotting, and Oil Red O staining were employed to detect the adipogenic differentiation of ۳T۳-L۱ cells and formation of beige adipocytes. The cardiomyocytes co-cultured with beige adipocytes were used for OGD treatment. Cell apoptosis was analyzed by flow cytometry. The lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity were analyzed using commercially available kits.Results: The decrease of LSD۱ was related to the age-dependent loss of beige adipocytes in mice EpAT. LSD۱ knockdown inhibited the adipogenic differentiation of ۳T۳-L۱ cells and formation of beige adipocytes. The down-regulation of LSD۱ in ۳T۳-L۱ cells decreased the protective effect of mature adipocytes on OGD-injured cardiomyocytes.Conclusion: The decreased expression of LSD۱ in mice EpAT was associated with age-dependent ablation of beige adipocytes. The protective effect of beige adipocytes on OGD-injured cardiomyocytes is reduced by knockdown of LSD۱ in adipocytes. The present study provided exciting insights into establishing novel therapies against age-dependent cardiac diseases.

Keywords:

Beige adipocyte , Cardiomyocyte , Epicardial adipose tissue , Lysine-specific demethylase ۱ , Oxygen and glucose-deprivation