TY - JOUR
T1 - Melatonin ameliorates simulated-microgravity-induced mitochondrial dysfunction and lipid metabolism dysregulation in hepatocytes
AU - Xiong, Yue
AU - Ma, Chiyuan
AU - Li, Qin
AU - Zhang, Wenya
AU - Zhao, Huashan
AU - Ren, Peigen
AU - Zhang, Ke
AU - Lei, Xiaohua
N1 - Publisher Copyright:
© 2023 Federation of American Societies for Experimental Biology.
PY - 2023/9
Y1 - 2023/9
N2 - The liver is an essential multifunctional organ, which constantly communicates with nearly all tissues. It has raised the concern that microgravity exposure can lead to liver dysfunction and metabolic syndromes. However, molecular mechanisms and intervention measures of the adverse effects of microgravity on hepatocytes are limited. In this study, we utilized the random positioning machine culture system to investigate the adverse effects on hepatocytes under simulated microgravity (SMG). Our results showed that SMG impaired hepatocyte viability, causing cell cycle arrest and apoptosis. Compared to normal gravity, it also triggered lipid accumulation, elevated triglyceride (TG) and ROS levels, and impaired mitochondria function in hepatocytes. Furthermore, RNA sequencing results showed that SMG upregulated genes implicated in lipid metabolisms, including PPARγ, PLIN2, CD36, FABPs, etc. Importantly, all these defects can be suppressed by melatonin, a potent antioxidant secreted by the pineal gland, suggesting its potential use of therapeutic intervention.
AB - The liver is an essential multifunctional organ, which constantly communicates with nearly all tissues. It has raised the concern that microgravity exposure can lead to liver dysfunction and metabolic syndromes. However, molecular mechanisms and intervention measures of the adverse effects of microgravity on hepatocytes are limited. In this study, we utilized the random positioning machine culture system to investigate the adverse effects on hepatocytes under simulated microgravity (SMG). Our results showed that SMG impaired hepatocyte viability, causing cell cycle arrest and apoptosis. Compared to normal gravity, it also triggered lipid accumulation, elevated triglyceride (TG) and ROS levels, and impaired mitochondria function in hepatocytes. Furthermore, RNA sequencing results showed that SMG upregulated genes implicated in lipid metabolisms, including PPARγ, PLIN2, CD36, FABPs, etc. Importantly, all these defects can be suppressed by melatonin, a potent antioxidant secreted by the pineal gland, suggesting its potential use of therapeutic intervention.
KW - hepatic lipid accumulation
KW - melatonin
KW - mitochondrial dysfunction
KW - simulated microgravity
UR - http://www.scopus.com/inward/record.url?scp=85166784318&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85166784318&partnerID=8YFLogxK
U2 - 10.1096/fj.202301137R
DO - 10.1096/fj.202301137R
M3 - Article
C2 - 37552471
AN - SCOPUS:85166784318
SN - 0892-6638
VL - 37
JO - FASEB Journal
JF - FASEB Journal
IS - 9
M1 - e23132
ER -