Leptin receptor-expressing nucleus tractus solitarius neurons suppress food intake independently of GLP1 in mice
- 9 April 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
Abstract
Leptin receptor-expressing (LepRb-expressing) neurons of the nucleus tractus solitarius (NTS; LepRb(NTS) neurons) receive gut signals that synergize with leptin action to suppress food intake. NTS neurons that express preproglucagon (Ppg) (and that produce the food intake-suppressing PPG cleavage product glucagon-like peptide-1 [GLP1]) represent a subpopulation of mouse LepRb(NTS) cells. Using Lein(cre), Ppg(cre), and Ppg(fl) mouse lines, along with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we examined roles for Ppg in GLP1(NTS) and LepRP(NTS) cells for the control of food intake and energy balance. We found that the cre-dependent ablation of NTS Ppg(fl) early in development or in adult mice failed to alter energy balance, suggesting the importance of pathways independent of NTS GLP1 for the long-term control of food intake. Consistently, while activating GLP1(NTS) cells decreased food intake, LepRb(NTS) cells elicited larger and more durable effects. Furthermore, while the ablation of NTS Ppg(fl) blunted the ability of GLP1(NTS) neurons to suppress food intake during activation, it did not impact the suppression of food intake by LepRb(NTS) cells. While Ppg/GLP1-mediated neurotransmission plays a central role in the modest appetite-suppressing effects of GLP1(NTS) cells,additional pathways engaged by LepRb(NTS) cells dominate for the suppression of food intake.Keywords
Funding Information
- NIDDK (1P01DK117821,DK082480,DK104999)
- American Diabetes Association (1-16-PDF-021)
- AstraZeneca (no grant number)
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