C/EBPα induces adipogenesis through PPARγ: a unified pathway C/EBPα and PPARγ are critical transcription factors in adipogenesis, but their exact roles have been difficult to determine due to their mutual regulation. This study shows that C/EBPα and PPARγ function in a single pathway of fat cell development, with PPARγ being the proximal effector of adipogenesis. Adipogenesis is the process by which undifferentiated precursor cells become fat cells. It has become a major area of study due to the increasing prevalence of obesity and the availability of cell culture models. The transcriptional cascade promoting fat cell differentiation involves several transcription factors, including C/EBPα, C/EBPβ, C/EBPδ, PPARγ, and ADD1/SREBP1c. C/EBPβ and C/EBPδ induce low levels of PPARγ and C/EBPα, which then induce each other's expression in a positive feedback loop that promotes and maintains the differentiated state. Loss-of-function studies show that PPARγ is required for adipogenesis in both in vitro and in vivo models. Cells lacking PPARγ express reduced levels of C/EBPα. Conversely, fibroblasts lacking C/EBPα have reduced adipogenic potential and express reduced levels of PPARγ. Adding PPARγ back to C/EBPα-deficient fibroblasts restores their ability to accumulate lipid and activate adipogenesis markers. However, the converse has not been tested. The presence of exogenously applied C/EBPα in the absence of PPARγ has not been shown to promote adipogenesis due to technical limitations. Two models of adipogenesis are presented: one where PPARγ and C/EBPα induce each other's expression and can act independently, and another where PPARγ is the direct regulator of adipogenesis, while C/EBPα maintains PPARγ expression and promotes insulin sensitivity. To determine which model is more accurate, a fibroblast cell line lacking PPARγ was created. These cells showed that the adipogenic action of C/EBPα is entirely dependent on PPARγ. Ectopic PPARγ can stimulate adipogenesis in PPARγ-deficient fibroblasts, but C/EBPα cannot. This indicates that PPARγ is the proximal effector of adipogenesis, and C/EBPα's role is to maintain PPARγ expression and promote insulin sensitivity. The study supports the model where PPARγ is the direct regulator of adipogenesis, and C/EBPα plays a role in maintaining PPARγ expression and promoting insulin sensitivity.C/EBPα induces adipogenesis through PPARγ: a unified pathway C/EBPα and PPARγ are critical transcription factors in adipogenesis, but their exact roles have been difficult to determine due to their mutual regulation. This study shows that C/EBPα and PPARγ function in a single pathway of fat cell development, with PPARγ being the proximal effector of adipogenesis. Adipogenesis is the process by which undifferentiated precursor cells become fat cells. It has become a major area of study due to the increasing prevalence of obesity and the availability of cell culture models. The transcriptional cascade promoting fat cell differentiation involves several transcription factors, including C/EBPα, C/EBPβ, C/EBPδ, PPARγ, and ADD1/SREBP1c. C/EBPβ and C/EBPδ induce low levels of PPARγ and C/EBPα, which then induce each other's expression in a positive feedback loop that promotes and maintains the differentiated state. Loss-of-function studies show that PPARγ is required for adipogenesis in both in vitro and in vivo models. Cells lacking PPARγ express reduced levels of C/EBPα. Conversely, fibroblasts lacking C/EBPα have reduced adipogenic potential and express reduced levels of PPARγ. Adding PPARγ back to C/EBPα-deficient fibroblasts restores their ability to accumulate lipid and activate adipogenesis markers. However, the converse has not been tested. The presence of exogenously applied C/EBPα in the absence of PPARγ has not been shown to promote adipogenesis due to technical limitations. Two models of adipogenesis are presented: one where PPARγ and C/EBPα induce each other's expression and can act independently, and another where PPARγ is the direct regulator of adipogenesis, while C/EBPα maintains PPARγ expression and promotes insulin sensitivity. To determine which model is more accurate, a fibroblast cell line lacking PPARγ was created. These cells showed that the adipogenic action of C/EBPα is entirely dependent on PPARγ. Ectopic PPARγ can stimulate adipogenesis in PPARγ-deficient fibroblasts, but C/EBPα cannot. This indicates that PPARγ is the proximal effector of adipogenesis, and C/EBPα's role is to maintain PPARγ expression and promote insulin sensitivity. The study supports the model where PPARγ is the direct regulator of adipogenesis, and C/EBPα plays a role in maintaining PPARγ expression and promoting insulin sensitivity.