Adipose tissues collectively as an endocrine organ and energy storage are crucial for systemic metabolic homeostasis. The major cell type in the adipose tissue, the adipocytes or fat cells, are remarkably plastic and can increase or decrease their size and number to adapt to changes in systemic or local metabolism. Changes in adipocyte size occur through hypertrophy or atrophy, and changes in cell numbers mainly involve de novo generation of new cells or death of existing cells. Recently, dedifferentiation, whereby a mature adipocyte is reverted to an undifferentiated progenitor-like status, has been reported as a mechanism underlying adipocyte plasticity. Dedifferentiation of mature adipocytes has been observed under both physiological and pathological conditions. This review covers several aspects of adipocyte dedifferentiation, its relevance to adipose tissue function, molecular pathways that drive dedifferentiation, and the potential of therapeutic targeting adipocyte dedifferentiation in human health and metabolic diseases.

The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca²⁺ stimulation and extracellular signal–regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca²⁺-ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.

Adipogenesis is tightly controlled by a complex network of transcription factors acting at different stages of differentiation. Kruppel-like factors (KLFs) as a family of zinc-finger transcription factors play diverse roles during cell differentiation and development in mammals. In the present study, we showed that KLF13 acts as a key regulator regulating porcine adipocyte differentiation. The expression of KLF13 was markedly up-regulated during the early stage of porcine adipocyte differentiation, which was followed by expression of PPARγ. Porcine adipocyte differentiation was significantly attenuated by the addition of siRNA against KLF13, whereas overexpression of KLF13 resulted in enhanced porcine adipocyte differentiation. Using promoter deletion and mutation analysis, we identified a KLF13-binding site within −593/-577 region of the porcine PPARγ proximal promoter, indicating that KLF13 directly interacts with porcine PPARγ promoter. However, inhibition of KLF13 by siRNA did not impair mouse adipocyte differentiation. In addition, knockdown and/or overexpression of KLF13 in 3 T3-L1 cells all did not influence expression of PPARγ2. Collectively, our results suggest that KLF13 exist as a key pro-adipogenic transcription factor through transactivating PPARγ expression in porcine adipocyte differentiation, whereas no such effect was detected in mouse adipocyte differentiation.

Obesity is a critical risk factor causing the development of metabolic diseases and cancers. Its increasing prevalence worldwide has aroused great concerns of the researchers on adipose development and metabolic function. During adipose expansion, adipogenesis is a way to store lipids as well as to avoid lipotoxicity in other tissues, and may be an approach to offset the negative metabolic effects of obesity. In this Review, the transcriptional regulation of adipogenesis is outlined to characterize numerous biological processes in research on the determination of adipocyte fate and regulation of adipogenic differentiation. Notably, one of the post‐transcriptional modifications of mRNA, namely, N⁶‐methyladenosine (m⁶A), has been recently found to play a role in adipogenesis. Here, the roles of m⁶A‐related enzymes and proteins in adipogenesis, with a particular focus on how these m⁶A‐related proteins function at different stages of adipogenesis, are mainly discussed. The Review also highlights the coordination role of the transcriptional and post‐transcriptional (RNA m⁶A methylation) regulation in adipogenesis and related biological processes. In this context, a better understanding of adipogenesis at both the transcriptional and post‐transcriptional levels may facilitate the development of novel strategies to improve metabolic health in obesity.