Adipose tissue, primarily composed of adipocytes, plays a critical role in maintaining energy and metabolic homeostasis. Adipogenesis occurs in two stages: commitment of mesenchymal stem cells (MSCs) to a preadipocyte fate and terminal differentiation. Preadipocyte commitment and competency are regulated by cell shape and extracellular matrix (ECM) remodeling, modulating WNT and RHO GTPase signaling. Adipogenic stimuli induce terminal differentiation through epigenomic activation of PPARγ, which, along with C/EBP transcription factors, maintains adipocyte gene expression. Understanding these mechanisms may identify therapeutic targets for metabolic diseases. Adipose tissue is a complex organ regulating energy homeostasis, composed of adipocytes, fibroblasts, endothelial cells, nerves, and immune cells. It functions as an endocrine organ, and dysfunction is central to metabolic diseases like obesity, type 2 diabetes, and cancer cachexia. There are two main types of adipose tissue: white (WAT) and brown (BAT). WAT is the main type in humans, while BAT is involved in thermogenesis. Recent studies have identified metabolically active BAT in humans, challenging previous assumptions. Adipogenesis involves two phases: commitment and terminal differentiation. MSCs differentiate into adipocytes, osteoblasts, myocytes, and chondrocytes. Preadipocytes are defined by their ability to differentiate upon adipogenic stimuli. Recent studies have identified preadipocytes in vivo, showing their role in adipose development. WNT and TGFβ signaling pathways regulate adipogenesis, with WNT signaling inhibiting adipogenesis and TGFβ having conflicting roles in vitro and in vivo. The ECM's composition and stiffness regulate adipogenesis, influencing lineage commitment and cell fate decisions. Mechanical cues, such as ECM stiffness and tension, affect adipocyte differentiation. Cell shape and signaling pathways, including RHO GTPase signaling, also influence adipogenesis. Transcriptional factors like ZFP423 and TCF7L1 regulate adipogenic competency, while PPARγ and C/EBP proteins are central to terminal differentiation. Epigenomic regulation, including histone modifications and DNA methylation, plays a key role in adipocyte differentiation. PPARγ is essential for adipogenesis, and its activation is regulated by various factors, including circadian rhythm genes. Histone acetylation and methylation are critical for maintaining mature adipocyte gene expression. PPARγ and C/EBP proteins also regulate each other in a positive feedback loop. Brown adipocyte differentiation requires PPARγ and C/EBP activity, with PRDM16 and PGC1α playing key roles. These factors regulate thermogenic gene expression and metabolic function. Conservation of adipocyte gene activation across species highlights the importance of epigenomic regulation in adipogenesis. Understanding these mechanisms may lead to new therapeutic strategies for metabolic diseasesAdipose tissue, primarily composed of adipocytes, plays a critical role in maintaining energy and metabolic homeostasis. Adipogenesis occurs in two stages: commitment of mesenchymal stem cells (MSCs) to a preadipocyte fate and terminal differentiation. Preadipocyte commitment and competency are regulated by cell shape and extracellular matrix (ECM) remodeling, modulating WNT and RHO GTPase signaling. Adipogenic stimuli induce terminal differentiation through epigenomic activation of PPARγ, which, along with C/EBP transcription factors, maintains adipocyte gene expression. Understanding these mechanisms may identify therapeutic targets for metabolic diseases. Adipose tissue is a complex organ regulating energy homeostasis, composed of adipocytes, fibroblasts, endothelial cells, nerves, and immune cells. It functions as an endocrine organ, and dysfunction is central to metabolic diseases like obesity, type 2 diabetes, and cancer cachexia. There are two main types of adipose tissue: white (WAT) and brown (BAT). WAT is the main type in humans, while BAT is involved in thermogenesis. Recent studies have identified metabolically active BAT in humans, challenging previous assumptions. Adipogenesis involves two phases: commitment and terminal differentiation. MSCs differentiate into adipocytes, osteoblasts, myocytes, and chondrocytes. Preadipocytes are defined by their ability to differentiate upon adipogenic stimuli. Recent studies have identified preadipocytes in vivo, showing their role in adipose development. WNT and TGFβ signaling pathways regulate adipogenesis, with WNT signaling inhibiting adipogenesis and TGFβ having conflicting roles in vitro and in vivo. The ECM's composition and stiffness regulate adipogenesis, influencing lineage commitment and cell fate decisions. Mechanical cues, such as ECM stiffness and tension, affect adipocyte differentiation. Cell shape and signaling pathways, including RHO GTPase signaling, also influence adipogenesis. Transcriptional factors like ZFP423 and TCF7L1 regulate adipogenic competency, while PPARγ and C/EBP proteins are central to terminal differentiation. Epigenomic regulation, including histone modifications and DNA methylation, plays a key role in adipocyte differentiation. PPARγ is essential for adipogenesis, and its activation is regulated by various factors, including circadian rhythm genes. Histone acetylation and methylation are critical for maintaining mature adipocyte gene expression. PPARγ and C/EBP proteins also regulate each other in a positive feedback loop. Brown adipocyte differentiation requires PPARγ and C/EBP activity, with PRDM16 and PGC1α playing key roles. These factors regulate thermogenic gene expression and metabolic function. Conservation of adipocyte gene activation across species highlights the importance of epigenomic regulation in adipogenesis. Understanding these mechanisms may lead to new therapeutic strategies for metabolic diseases