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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #395827
Research Project: Molecular, Cellular, and Regulatory Aspects of Obesity Development

Location: Children's Nutrition Research Center

Title: A neural basis for brain leptin action on reducing type 1 diabetic hyperglycemia

Author
item FAN, SHENGJIE - Shanghai University
item XU, YUANZHONG - University Of Texas Health Science Center
item LU, YUNGANG - University Of Texas Health Science Center
item JIANG, ZHIYING - University Of Texas Health Science Center
item LI, HONGLI - University Of Texas Health Science Center
item MORRILL, JESSIE - University Of Texas Health Science Center
item CAI, JING - University Of Texas Health Science Center
item WU, QI - Children'S Nutrition Research Center (CNRC)
item XU, YONG - Children'S Nutrition Research Center (CNRC)
item XUE, MINGSHAN - Baylor College Of Medicine
item ARENKIEL, BENJAMIN - Baylor College Of Medicine
item HUANG, CHENG - Shanghai University
item 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.