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

• Published in: Journal of cellular physiology Vol. 235; no. 10; pp. 6725 - 6735
• Main Authors: Sato, Tomohiko, Vargas, Diana, Miyazaki, Kakushin, Uchida, Kaoru, Ariyani, Winda, Miyazaki, Mitsue, Okada, Junichi, Lizcano, Fernando, Koibuchi, Noriyuki, Shimokawa, Noriaki
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2020
• Subjects: 3T3-L1 Cells; Accumulation; Adipocytes; Adipocytes - metabolism; Adipogenesis; Adipogenesis - physiology; Adipose tissue; Adipose Tissue, White - metabolism; Animals; Cardiovascular diseases; Cell differentiation; Cell Differentiation - physiology; Cell Line; Cell Nucleus - metabolism; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Differentiation; DNA chips; DNA microarray; DNA microarrays; Down-Regulation - physiology; EID1; Energy expenditure; Food intake; Glucose; Glucose - metabolism; Glucose Transport Proteins, Facilitative - metabolism; Glucose transporter; Glycerol; Glycerolphosphate Dehydrogenase - metabolism; GPDH; Image analysis; Image processing; Lipid Metabolism - physiology; Lipids; Metabolic disorders; Mice; Nuclear Proteins - metabolism; Obesity - metabolism; Preadipocytes; preadipocytes 3T3‐L1; Promoter Regions, Genetic - genetics; Repressor Proteins - metabolism; Risk analysis; Risk factors; Transcription; Translocation; Triglycerides; Triglycerides - metabolism; DNA microarray; EID1; adipogenesis; GPDH; preadipocytes 3T3-L1
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29567

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. 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. 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.