Location: Children's Nutrition Research Center
Title: A neural basis for brain leptin action on reducing type 1 diabetic hyperglycemiaAuthor
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FAN, SHENGJIE - Shanghai University |
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XU, YUANZHONG - University Of Texas Health Science Center |
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LU, YUNGANG - University Of Texas Health Science Center |
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JIANG, ZHIYING - University Of Texas Health Science Center |
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LI, HONGLI - University Of Texas Health Science Center |
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MORRILL, JESSIE - University Of Texas Health Science Center |
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CAI, JING - University Of Texas Health Science Center |
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WU, QI - Children'S Nutrition Research Center (CNRC) |
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XU, YONG - Children'S Nutrition Research Center (CNRC) |
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XUE, MINGSHAN - Baylor College Of Medicine |
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ARENKIEL, BENJAMIN - Baylor College Of Medicine |
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HUANG, CHENG - Shanghai University |
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TONG, QINGCHUN - University Of Texas Health Science Center |
Submitted to: Nature Communications
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 4/7/2021 Publication Date: 5/11/2021 Citation: Fan, S., Xu, Y., Lu, Y., Jiang, Z., Li, H., Morrill, J., Cai, J., Wu, Q., Xu, Y., Xue, M., Arenkiel, B., Huang, C., Tong, Q. 2021. A neural basis for brain leptin action on reducing type 1 diabetic hyperglycemia. Nature Communications. 12. Article 2662. https://doi.org/10.1038/s41467-021-22940-4. DOI: https://doi.org/10.1038/s41467-021-22940-4 Interpretive Summary: Type 1 diabetes (T1D) is a very prevalent disease, but the only current treatment option is insulin. Recent studies in rodents have shown that the hormone leptin is capable of reducing high blood sugar in T1D. Researchers investigated the neurons related to leptin's effect on T1D. Our results showed that leptin receptor-expressing neurons are selectively activated in T1D. We also show that this activation is reversed by leptin. Our findings provide an understanding of the mechanism underlying leptin action. This work is important for a full understanding of T1D, which may lead to better treatment strategies. Technical Abstract: Central leptin action rescues type 1 diabetic (T1D) hyperglycemia; however, the underlying mechanism and the identity of mediating neurons remain elusive. Here, we show that leptin receptor (LepR)-expressing neurons in arcuate (LepRArc) are selectively activated in T1D. Activation of LepRArc neurons, Arc GABAergic (GABAArc) neurons, or arcuate AgRP neurons, is able to reverse the leptin’s rescuing effect. Conversely, inhibition of GABAArc neurons, but not AgRP neurons, produces leptin-mimicking rescuing effects. Further, AgRP neuron function is not required for T1D hyperglycemia or leptin’s rescuing effects. Finally, T1D LepRArc neurons show defective nutrient sensing and signs of cellular energy deprivation, which are both restored by leptin, whereas nutrient deprivation reverses the leptin action. Our results identify aberrant activation of LepRArc neurons owing to energy deprivation as the neural basis for T1D hyperglycemia and that leptin action is mediated by inhibiting LepRArc neurons through reversing energy deprivation. |