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Forming functional fat: a growing understanding of adipocyte differentiation

Nature Reviews Molecular Cell Biology volume 12, pages 722–734 (2011)Cite this article

Subjects

Key Points

  • Adipogenesis is a highly regulated process that converts fibroblast-like precursor cells into round and lipid-laden adipocytes.

  • White and brown adipocyte differentiation share many key important features, such as a requirement for the master adipogenic regulator, peroxisome proliferator-activated receptor-γ (PPARγ), but they also have important differences.

  • The identification of committed precursor cells within adipose tissue has been important for understanding adipogenesis in vivo.

  • Adipogenic stimuli activate signalling pathways that coordinate transcription factors to promote stem cell commitment to an adipogenic fate.

  • Extensive epigenomic modifications underlie the commitment and stability of differentiation into adipocytes.

Abstract

Adipose tissue, which is primarily composed of adipocytes, is crucial for maintaining energy and metabolic homeostasis. Adipogenesis is thought to occur in two stages: commitment of mesenchymal stem cells to a preadipocyte fate and terminal differentiation. Cell shape and extracellular matrix remodelling have recently been found to regulate preadipocyte commitment and competency by modulating WNT and RHO-family GTPase signalling cascades. Adipogenic stimuli induce terminal differentiation in committed preadipocytes through the epigenomic activation of peroxisome proliferator-activated receptor-γ (PPARγ). The coordination of PPARγ with CCAAT/enhancer-binding protein (C/EBP) transcription factors maintains adipocyte gene expression. Improving our understanding of these mechanisms may allow us to identify therapeutic targets against metabolic diseases that are rapidly becoming epidemic globally.

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Figure 1: Cues influencing white adipogenic progression.
Figure 2: Relationship between white and brown adipogenesis.
Figure 3: WNT signalling in adipogenesis.
Figure 4: RHO-family GTPases in adipogenesis.
Figure 5: Activation of C/EBPs and PPARγ during terminal differentiation.

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Acknowledgements

We thank P. Seale and members of the Lazar laboratory for insightful discussions. Work on adipogenesis in the Lazar laboratory is supported by US National Institutes of Health grant number DK49780. A.G.C. was supported by the Gilliam Fellowship from the Howard Hughes Medical Institute. We apologize for not being able to discuss and cite all worthy papers and topics as a result of space limitations.

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  1. Division of Endocrinology, Department of Medicine, Department of Genetics and The Institute for Diabetes, Diabetes and Metabolism, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Ana G. Cristancho & Mitchell A. Lazar

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Glossary

Type 2 diabetes

A chronic disease that is characterized by increased blood glucose and is related to insulin resistance and pancreatic failure.

Cancer cachexia

Loss of weight, muscle atrophy, fatigue, weakness and loss of appetite in the setting of cancer.

Lipodystrophies

Reduced or abnormally redistributed adipose compartments (acquired or genetic).

Unilocular

Having one large lipid droplet.

Thermogenesis

The process of producing heat.

Fluorodeoxyglucose positron emission tomography

A molecular imaging technique that uses a labelled glucose analogue.

Epigenomic

Of the epigenome; that is, chromatin modifications, including DNA methylation and histone modification, that regulate gene expression and function without a corresponding alteration in DNA sequence.

Subscapular

Referring to the region below the scapula (the shoulder blade).

Uncoupling protein 1

(UCP1). A mitochondrial protein that dissociates oxidative phosphorylation from energy production, leading to increased thermogenesis.

A-Zip mice

Mice in which a dominant-negative transcription factor that interferes with CCAAT/enhancer-binding protein (C/EBP) function is expressed by adipocytes, leading to lipodystrophy.

Integrin

A heterodimeric, cation-dependent cell surface receptor that attaches cells to their surrounding environment, connecting extracellular matrix cues to intracellular signalling.

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Cristancho, A., Lazar, M. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol 12, 722–734 (2011). https://doi.org/10.1038/nrm3198

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