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Brown and Beige Adipose Tissues in Health and Disease

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ABSTRACT

Brown and beige adipocytes arise from distinct developmental origins. Brown adipose tissue (BAT) develops embryonically from precursors that also give to skeletal muscle. Beige fat develops postnatally and is highly inducible. Beige fat recruitment is mediated by multiple mechanisms, including de novo beige adipogenesis and white‐to‐brown adipocyte transdifferentiaiton. Beige precursors reside around vasculatures, and proliferate and differentiate into beige adipocytes. PDGFRα+Ebf2+ precursors are restricted to beige lineage cells, while another PDGFRα+ subset gives rise to beige adipocytes, white adipocytes, or fibrogenic cells. White adipocytes can be reprogramed and transdifferentiated into beige adipocytes. Brown and beige adipocytes display many similar properties, including multilocular lipid droplets, dense mitochondria, and expression of UCP1. UCP1‐mediated thermogenesis is a hallmark of brown/beige adipocytes, albeit UCP1‐independent thermogenesis also occurs. Development, maintenance, and activation of BAT/beige fat are guided by genetic and epigenetic programs. Numerous transcriptional factors and coactivators act coordinately to promote BAT/beige fat thermogenesis. Epigenetic reprograming influences expression of brown/beige adipocyte‐selective genes. BAT/beige fat is regulated by neuronal, hormonal, and immune mechanisms. Hypothalamic thermal circuits define the temperature setpoint that guides BAT/beige fat activity. Metabolic hormones, paracrine/autocrine factors, and various immune cells also play a critical role in regulating BAT/beige fat functions. BAT and beige fat defend temperature homeostasis, and regulate body weight and glucose and lipid metabolism. Obesity is associated with brown/beige fat deficiency, and reactivation of brown/beige fat provides metabolic health benefits in some patients. Pharmacological activation of BAT/beige fat may hold promise for combating metabolic diseases. © 2017 American Physiological Society. Compr Physiol 7:1281‐1306, 2017.

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Figure 1. Figure 1. A schematic representation of the core thermal circuitry. DRG, dorsal root ganglia; LPB, lateral parabrachial nucleus; MnPO, median preoptic subnucleus; MPA, medial preoptic area; DMH/DHA, dorsomedial hypothalamus/dorsal hypothalamic area; rRPa, the rostral raphe pallidus; IML, intermediolateral nucleus.


Figure 1. A schematic representation of the core thermal circuitry. DRG, dorsal root ganglia; LPB, lateral parabrachial nucleus; MnPO, median preoptic subnucleus; MPA, medial preoptic area; DMH/DHA, dorsomedial hypothalamus/dorsal hypothalamic area; rRPa, the rostral raphe pallidus; IML, intermediolateral nucleus.
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Teaching Material

L. Rui. Brown and Beige Adipose Tissues in Health and Disease. Compr Physiol 7: 2017, 1281-1306. doi:10.1002/cphy.c170001

Didactic Synopsis

Major Teaching Points:

  • Understanding of the development, maintenance, and activation of brown fat and beige fat is critical to appreciate body temperature homeostasis, energy balance, and body weight control.
  • Understanding of the thermogenic machinery is necessary to explain the metabolic function of brown fat and beige fat.
  • Understanding of neuronal, humoral, and immune regulation of brown fat and beige fat is important to appreciate the role of brown fat and beige fat in obesity and metabolic disease development.
  • Understanding of adipose signaling pathways, genetic programs, and epigenetic reprograming is critical to appreciate brown and beige adipogenesis.
  • Understanding of human brown/beige fat characteristics is important to guide development of new obesity and metabolic disease therapies.

Didactic Legends

The figures—in a freely downloadable PowerPoint format—can be found on the Images tab along with the formal legends published in the article. The following legends to the same figures are written to be useful for teaching.

Figure 1. Teaching Points: A schematic representation of the core thermal circuitry. DRG, dorsal root ganglia; LPB, lateral parabrachial nucleus; MnPO, median preoptic subnucleus; MPA, medial preoptic area; DMH/DHA, dorsomedial hypothalamus/dorsal hypothalamic area; rRPa, the rostral raphe pallidus; IML, intermediolateral nucleus.


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Hormonal Regulation of Adipogenesis
Central Nervous System Regulation of Brown Adipose Tissue

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How to Cite

Liangyou Rui. Brown and Beige Adipose Tissues in Health and Disease. Compr Physiol 2017, 7: 1281-1306. doi: 10.1002/cphy.c170001