Page 32 - A. Aging

[A. Aging-18]

TMBIM6 regulates aging-associated hepatic steatosis

Kashi Raj Bhattarai¹, Hyun- Kyoung Kim¹, Manoj Chaudhary¹, Hyung- Ryong Kim², Han-Jung Chae¹˙*

¹Department of Pharmacology and Institute of New Drug Development, School of Medicine, Jeonbuk National

University, Jeonju-si 54896, Republic of Korea, ²College of Dentistry, Dankook University, Cheonan 31116, Republic
of Korea

Aging is a process that involves a very complex mechanism, accompanied by the declining capacity of the cellular

machinery, which leads to misfolded and aggregated proteins, resulting ER Stress. The main objective of our study

was to investigate the effect of TMBIM6 (Transmembrane BAX Inhibitor Motif Containing 6) on aging-associated
hepatic steatosis. We categorized wild-type (WT) and TMBIM6 knockout (KO) mice into young, middle, and old
groups, and observed the effect on hepatic lipid accumulation in normal food diet condition. The expression of

TMBIM6 mRNA and protein was found to be decreased in aging mice. We observed that the TMBIM6 deficient
aged mice gained bodyweight, high hepatic triglyceride level, and increased hepatic lipid droplets when compared

with its WT counterparts. TMBIM6 KO aged mice increased oxidative stress, TUNEL positive cells, expression of
cleaved caspases 7 and 12. Loss of TMBIM6 induced aberrant ER stress response following hepatic cell death.

Collectively, these results suggest that aging-associated steatosis is regulated by TMBIM6 through the regulation of
ER stress and proteostasis.