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Adipocyte differentiation from the inside out

Key Points

  • Adipogenesis is a complex process that involves the integration of many different signalling pathways and transcription factors.

  • The transcriptional pathway in adipogenesis centres on the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ). Other transcription factors, such as CCAAT-enhancer-binding proteins (C/EBPs) and Krüppel-like factors (KLFs), also have crucial roles.

  • Nuclear cofactors modulate the adipogenic process by binding to and activating (or repressing) important transcriptional components of the adipogenic pathway.

  • Adipogenesis is regulated by several highly conserved signalling pathways, including the anti-adipogenic Wnt–β-catenin and hedgehog-signalling cascades, as well as the pro-adipogenic insulin-growth factor-1/insulin and fibroblast-growth-factor pathways.

  • Some signalling pathways, such as those that involve bone morphogenetic proteins and mitogen-activated protein kinase, can be pro-adipogenic or anti-adipogenic depending on the cellular context and developmental timing.

  • Factors that promote adipogenesis tend to repress alternative mesenchymal fates such as osteogenesis and myogenesis.

  • Excess adipogenesis is not a cause of obesity; however, evidence of increased adipogenesis can be observed in the obese state.

Abstract

Improved knowledge of all aspects of adipose biology will be required to counter the burgeoning epidemic of obesity. Interest in adipogenesis has increased markedly over the past few years with emphasis on the intersection between extracellular signals and the transcriptional cascade that regulates adipocyte differentiation. Many different events contribute to the commitment of a mesenchymal stem cell to the adipocyte lineage including the coordination of a complex network of transcription factors, cofactors and signalling intermediates from numerous pathways.

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Figure 1: How do we study adipogenesis?
Figure 2: A complex transcriptional cascade regulates adipogenesis.
Figure 3: Regulation of adipogenesis by extracellular factors.

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Acknowledgements

We would like to thank members of the Rosen and MacDougald laboratories for helpful discussions.

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Glossary

Insulin resistance

A state in which the response to the hormone insulin is blunted. Insulin resistance can be seen at the cellular, organ, or organismal level.

Mesenchymal stem cells

Pluripotent cells with the capacity to differentiate into a limited set of cell types, including myocytes, chondrocytes, osteocytes and adipocytes.

Mitotic clonal expansion

A phase in 3T3-L1 adipocyte differentiation that involves one or two rounds of cell division that occur after confluent cells are treated with differentiation-inducing agents.

Lipodystrophy

A condition that is characterized by absent or reduced amounts of adipose tissue, with adverse health consequences due to lipid deposition in ectopic sites such as liver, muscle and other organs.

Sirtuins

A highly conserved family of enzymes with NAD+− dependent deacetylase activity, with various effects on longevity and metabolism.

Zucker rat

A genetic model of obesity that has a spontaneous mutation in the leptin receptor.

Necdin

A protein with growth-suppressing properties that is expressed predominantly in post-mitotic cells.

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Rosen, E., MacDougald, O. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7, 885–896 (2006). https://doi.org/10.1038/nrm2066

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