Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation via activating its enzymatic activity

Department of Biological Sciences, KAIST, Daejeon 305-701, Republic of Korea.
The Journal of Lipid Research (Impact Factor: 4.42). 06/2012; 53(9):1864-76. DOI: 10.1194/jlr.M026567
Source: PubMed


Acetylation is one of the most crucial post-translational modifications that affect protein function. Protein lysine acetylation is catalyzed by acetyltransferases, and acetyl-CoA functions as the source of the acetyl group. Additionally, acetyl-CoA plays critical roles in maintaining the balance between carbohydrate metabolism and fatty acid synthesis. Here, we sought to determine whether lysine acetylation is an important process for adipocyte differentiation. Based on an analysis of the acetylome during adipogenesis, various proteins displaying significant quantitative changes were identified by LC-MS/MS. Of these identified proteins, we focused on malate dehydrogenase 1 (MDH1). The acetylation level of MDH1 was increased up to 6-fold at the late stage of adipogenesis. Moreover, overexpression of MDH1 in 3T3-L1 preadipocytes induced a significant increase in the number of cells undergoing adipogenesis. The introduction of mutations to putative lysine acetylation sites showed a significant loss of the ability of cells to undergo adipogenic differentiation. Furthermore, the acetylation of MDH1 dramatically enhanced its enzymatic activity and subsequently increased the intracellular levels of NADPH. These results clearly suggest that adipogenic differentiation may be regulated by the acetylation of MDH1 and that the acetylation of MDH1 is one of the cross-talk mechanisms between adipogenesis and the intracellular energy level.

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    • "In a recent study, Kim et al. (2012) found that increased acetylation of MDH-1 during adipogenesis dramatically enhanced its enzymatic activity. They proposed that this activity supports acetyl coenzyme A (acetyl-CoA) and NADPH in lipid synthesis by accelerating the citrate shuttle and that MDH-1 performs a key function as cross-talk mechanism between lipid synthesis and intracellular energy levels (Kim et al. 2012). The observed differences in relative body condition index of fin whale individuals with and without the fast MDH-1 electromorph does point to a link between MDH-1 and fin whale body condition. "
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    • "Lipid droplets of differentiating or mature brown adipocytes were stained by an Oil-red O staining method, as described previously (17-20). For a quantification analysis, the Oil-red O staining dye was extracted and quantified, as previously described (18,19). "
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    • "For virus production, GP2-293 cell lines were transfected using Lipofectamine 2000 (Gibco-Invitrogen ). The details of the transfection and transduction methods are described in our previous reports [4]. Infected cells were selected using a FACSAria cell sorter (BD Biosciences, San Jose, CA) and were further maintained in a growth medium. "
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    ABSTRACT: Previously, we identified proteins showing a differential acetylation pattern during adipogenic differentiation. Here, we examined the role of malate dehydrogenase 2 (MDH2) acetylation in the adipogenesis of 3T3-L1 preadipocytes. The acetylation level of MDH2 showed a dramatic increase during adipogenesis. The overexpression of wild-type MDH2 induced the significant acceleration of adipogenic differentiation. On the other hand, the acetylation-block mutant MDH2 showed significantly reduced adipogenic differentiation compared to the wild type. MDH2 acetylation enhances its enzymatic activity and consequently intracellular NADPH level. These results suggest that the acetylation of MDH2 was affected by the cellular energy state and subsequently regulated adipogenic differentiation.
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