Transcriptional control and hormonal response of thermogenic fat
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Figure 1
Transcriptional regulators of the thermogenic program. The PPARγ/RXR heterodimer plays a key role in regulating the development of all adipocytes. In thermogenic adipocytes (left), it also plays a major role in the regulation of the thermogenic program. A number of coactivators interact with PPARγ, including PGC1α which is regulated in part by IRF4, and PRDM16, which interacts with both PPARγ and C/EBPβ to drive thermogenesis. Other transcriptional regulators of thermogenesis include EBF2, which forms a ribonucleoprotein complex with Blinc1 to upregulate thermogenic genes. In white adipocytes (right) the PPARγ/RXR heterodimer instead interacts with TLE3, leading to the expression of white fat-selective genes. RB1, p107, and RIP140 also work in white adipocytes to inhibit the transcription of thermogenic genes.
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Figure 2
The regulation of thermogenic fat cells by secreted factors. A number of secreted factors regulate the thermogenic program in brown and beige cells. Cold exposure induces production of catecholamines from the sympathetic nervous system (solid teal line) and may also activate beige fat through a cell autonomous mechanism (dashed teal line). Anti-inflammatory macrophages can also produce catecholamines. FGF21, PG, RA, NPs, thyroid hormone, METRNL, BMPs, adenosine, and PTHrP regulate thermogenesis in brown and beige cells. In addition, the myokine irisin regulates thermogenesis in beige fat. FGF21, some BMPs, and adenosine have also been shown to be secreted by thermogenic adipocytes. To differentiate the factors that work in concert with central activation of thermogenesis and through β-adrenergic signaling from those that work through independent pathways, these independent factors, RA, adenosine, Irisin, and METRNL, have been bolded.
- © 2015 Society for Endocrinology
