Transcriptional control of adipose lipid handling by IRF4

By Jun Eguchi, Xun Wang, Songtao Yu, E. Kershaw, Patricia C Chiu, J. Dushay, J. Estall, U. Klein, E. Maratos-Flier, E. Rosen. Cell Metabolism, 2011

597 citations recorded by the source corpus.

Summary Adipocytes store triglyceride during periods of nutritional affluence and release free fatty acids during fasting through coordinated cycles of lipogenesis and lipolysis. While much is known about the acute regulation of these processes during fasting and feeding, less is understood about the transcriptional basis by which adipocytes control lipid handling. Here we show that interferon regulatory factor 4 (IRF4) is a critical determinant of the transcriptional response to nutrient availability in adipocytes. Fasting induces IRF4 in an insulin- and FoxO1-dependent manner. IRF4 is required for lipolysis, at least in part due to direct effects on the expression of adipocyte triglyceride lipase and hormone-sensitive lipase. Conversely, reduction of IRF4 enhances lipid synthesis. Mice lacking adipocyte IRF4 exhibit increased adiposity and deficient lipolysis. These studies establish a link between IRF4 and the disposition of calories in adipose tissue, with consequences for systemic metabolic homeostasis.

Subfields: Biochemistry, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/28fedb90b2ad83ea83eab45348778b2c093b0242

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biochemistry

1. B. Spiegelman
2. P. Seale
3. Gerald I. Shulman
4. Jun Wu
5. S. Kajimura

In Epidemiology

1. B. Spiegelman
2. S. Kajimura
3. P. Seale
4. Gerald I. Shulman
5. Jun Wu
6. E. Rosen
7. Haiming Cao
8. L. Sidossis

In Physiology

1. S. Kajimura
2. B. Spiegelman
3. P. Seale
4. Jun Wu
5. P. Cohen
6. Gerald I. Shulman
7. Alexander S. Banks
8. L. Sidossis

Citations in the corpus

• INFLAMMATION AND LIPID SIGNALING IN THE ETIOLOGY OF INSULIN RESISTANCE (2012, unknown): “Conversely, reduction of IRF4 enhances lipid synthesis (Eguchi et al., 2011).”
• What We Talk About When We Talk About Fat (2014, unknown): “Over a slightly longer timescale, insulin also represses lipolysis by transcriptionally silencing lipase genes via repression of the transcription factors FoxO1 and IRF4 (Chakrabarti and Kandror, 2009; Eguchi et al., 2011).”
• Molecular Mechanisms That Influence the Macrophage M1–M2 Polarization Balance (2014, background): “In a similar fashion, IRF4 is also involved in regulating the expression of genes associated with macrophage M2 polarization (49).”
• Ablation of PRDM16 and Beige Adipose Causes Metabolic Dysfunction and a Subcutaneous to Visceral Fat Switch (2014, methodology): “We next crossed Prdm16 and Adiponectin-cre mice (Eguchi et al., 2011) to generate mice with an adipocyte-specific knockout (KO) of Prdm16 (Adipo-PRDM16 KO).”
• The PI3K/AKT pathway in obesity and type 2 diabetes (2018, background): “PI3K, Phosphoinositide 3-kinase; AKT, protein kinase B; T2DM, type 2 diabetes mellitus; RTKs, receptor tyrosine kinases; GPCR, G-protein-coupled receptors; PIP2, phosphatidylinositol 4,5-biphosphate; PIP3, phosphatidylinositol 3,4,5-triphosphate; PTEN, Phosphatase and tensin homologue; PDK1, phospho”