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HLH-11 modulates lipid metabolism in response to nutrient availability

Author

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  • Yi Li

    (Peking University
    Peking University
    Peking University)

  • Wanqiu Ding

    (Peking University)

  • Chuan-Yun Li

    (Peking University)

  • Ying Liu

    (Peking University
    Peking University
    Peking University)

Abstract

The ability of organisms to sense nutrient availability and tailor their metabolic states to withstand nutrient deficiency is critical for survival. To identify previously unknown regulators that couple nutrient deficiency to body fat utilization, we performed a cherry-picked RNAi screen in C. elegans and found that the transcription factor HLH-11 regulates lipid metabolism in response to food availability. In well-fed worms, HLH-11 suppresses transcription of lipid catabolism genes. Upon fasting, the HLH-11 protein level is reduced through lysosome- and proteasome-mediated degradation, thus alleviating the inhibitory effect of HLH-11, activating the transcription of lipid catabolism genes, and utilizing fat. Additionally, lipid profiling revealed that reduction in the HLH-11 protein level remodels the lipid landscape in C. elegans. Moreover, TFAP4, the mammalian homolog of HLH-11, plays an evolutionarily conserved role in regulating lipid metabolism in response to starvation. Thus, TFAP4 may represent a potential therapeutic target for lipid storage disorders.

Suggested Citation

  • Yi Li & Wanqiu Ding & Chuan-Yun Li & Ying Liu, 2020. "HLH-11 modulates lipid metabolism in response to nutrient availability," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19754-1
    DOI: 10.1038/s41467-020-19754-1
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