Novel function of TREK-1 in regulating adipocyte differentiation and lipid accumulation.

1. Cell Death Dis. 2025 Mar 8;16(1):164. doi: 10.1038/s41419-025-07478-3.

Novel function of TREK-1 in regulating adipocyte differentiation and lipid accumulation.

Kim A(#)(1)(2), Jung S(#)(1)(3), Kim Y(#)(1), Jung J(1), Lee S(2)(3), Lee H(1)(3), Kim MJ(1), Park JY(3), Hwang EM(4), Lee J(5).

Author information: (1)Food Functionality Research Division, Korea Food Research Institute, Wanju, 55365, South Korea. (2)Brain Science Institute, Korea Institute of Science and Technology, Seoul, 02792, South Korea. (3)School of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul, 02841, South Korea. (4)Brain Science Institute, Korea Institute of Science and Technology, Seoul, 02792, South Korea. emhwang@kist.re.kr. (5)Food Functionality Research Division, Korea Food Research Institute, Wanju, 55365, South Korea. jklee@kfri.re.kr. (#)Contributed equally

K2P (two-pore domain potassium) channels, a diversified class of K+-selective ion channels, have been found to affect a wide range of physiological processes in the body. Despite their established significance in regulating proliferation and differentiation in multiple cell types, K2P channels’ specific role in adipogenic differentiation (adipogenesis) remains poorly understood. In this study, we investigated the engagement of K2P channels, specifically KCNK2 (also known as TREK-1), in adipogenesis using primary cultured adipocytes and TREK-1 knockout (KO) mice. Our findings showed that TREK-1 expression in adipocytes decreases substantially during adipogenesis. This typically causes an increased Ca2+ influx and alters the electrical potential of the cell membrane in 3T3-L1 cell lines. Furthermore, we observed an increase in differentiation and lipid accumulation in both 3T3-L1 cell lines and primary cultured adipocytes when the TREK-1 activity was blocked with Spadin, the specific inhibitors, and TREK-1 shRNA. Finally, our findings revealed that mice lacking TREK-1 gained more fat mass and had worse glucose tolerance when fed a high-fat diet (HFD) compared to the wild-type controls. The findings demonstrate that increase of the membrane potential at adipocytes through the downregulation of TREK-1 can influence the progression of adipogenesis.

© 2025. The Author(s).

DOI: 10.1038/s41419-025-07478-3 PMCID: PMC11890776 PMID: 40057491 [Indexed for MEDLINE]

Conflict of interest statement: Competing interests: The authors have declare no competing interests. Ethics approval and consent to participate: All animal experiments for animal care and handling were performed and approved by Institutional Animal Care and Use Committee of the Korea Institute of Science and Technology (IACUC, KIST-2020-068). This study does not involve human participants or human data; therefore, informed consent for participation and publication is not applicable.