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. 2020 Oct;235(10):6725-6735.
doi: 10.1002/jcp.29567. Epub 2020 Feb 13.

EID1 suppresses lipid accumulation by inhibiting the expression of GPDH in 3T3-L1 preadipocytes

Tomohiko Sato  1   2   3 , Diana Vargas  1   2   4 , Kakushin Miyazaki  2 , Kaoru Uchida  2 , Winda Ariyani  1 , Mitsue Miyazaki  2 , Junichi Okada  3 , Fernando Lizcano  4 , Noriyuki Koibuchi  1 , Noriaki Shimokawa  1   2
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EID1 suppresses lipid accumulation by inhibiting the expression of GPDH in 3T3-L1 preadipocytes

Tomohiko Sato et al. J Cell Physiol. 2020 Oct.

Abstract

The imbalance between food intake and energy expenditure causes high accumulation of triglycerides in adipocytes. Obesity is related with the increased lipid accumulation in white adipose tissue, which is a major risk factor for the development of metabolic disorders, such as type 2 diabetes and cardiovascular disease. This study highlights the role of E1A-like inhibitor of differentiation 1 (EID1) in the modulation of adipogenesis through the downregulation of glycerol-3-phosphate dehydrogenase (GPDH), which is a key enzyme in the synthesis of triglycerides and is considered to be a marker of adipogenesis. By analyzing DNA microarray data, we found that when EID1 is overexpressed in preadipocytes (3T3-L1 cells) during adipocyte differentiation, EID1 inhibits lipid accumulation through the downregulation of GPDH. In contrast, EID1 is not involved in the regulation of intracellular glucose via the translocation of glucose transporter. A confocal image analysis showed that EID1 is located in the nucleus of preadipocytes in the form of speckles, which could be involved as a regulator of the transcriptional process. We further confirmed that EID1 is able to bind to the promoter sequence of GPDH in the nucleus. These findings provide a molecular explanation for the inhibitory effect of EID1 on lipid accumulation in adipocytes.

Keywords: DNA microarray; EID1; GPDH; adipogenesis; preadipocytes 3T3-L1.

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