Biased signaling via NtsR1 restrains food intake and weight gain in obese mice
- 1Michigan State University
Abstract
Neurotensin receptor 1 (NTSR1) activation suppresses feeding and promotes weight loss but is limited by adverse effects associated with Gq signaling. SBI-553 is a {beta}-arrestin-biased allosteric modulator of NTSR1 that avoids these effects. We evaluated the effects of SBI-553 (5 or 12 mg/kg, i.p.) on food intake and body weight in lean and diet-induced obese mice. Neither dose altered metabolic parameters, locomotor activity, or wheel running. SBI-553 did not affect ad libitum feeding in lean mice; however, both doses acutely reduced high-fat diet intake in obese mice. While 5 mg/kg had no effect on hunger-induced feeding, 12 mg/kg suppressed refeeding in both chow- and high-fat-fed mice of both sexes and reduced weight regain in obese mice. These findings identify SBI-553 as a potential strategy for reducing food intake and supporting weight loss.
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BibTeX
@misc{ramirezvirella2026biased,
title = {{Biased signaling via NtsR1 restrains food intake and weight gain in obese mice}},
author = {J. Ramirez-Virella and K. Black and N. F. Dennis and R. Bugescu and K. Thompson and S. H. Olsen and L. M. Slosky and Z. A. McElligott and G. M. Leinninger},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.30.748142},
url = {https://www.biorxiv.org/content/10.64898/2026.08.30.748142v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Biased signaling via NtsR1 restrains food intake and weight gain in obese mice
AU - J. Ramirez-Virella
AU - K. Black
AU - N. F. Dennis
AU - R. Bugescu
AU - K. Thompson
AU - S. H. Olsen
AU - L. M. Slosky
AU - Z. A. McElligott
AU - G. M. Leinninger
PY - 2026
DA - 2026/08/30
PB - bioRxiv
DO - 10.64898/2026.08.30.748142
UR - https://www.biorxiv.org/content/10.64898/2026.08.30.748142v1
AB - Neurotensin receptor 1 (NTSR1) activation suppresses feeding and promotes weight loss but is limited by adverse effects associated with Gq signaling. SBI-553 is a {beta}-arrestin-biased allosteric modulator of NTSR1 that avoids these effects. We evaluated the effects of SBI-553 (5 or 12 mg/kg, i.p.) on food intake and body weight in lean and diet-induced obese mice. Neither dose altered metabolic parameters, locomotor activity, or wheel running. SBI-553 did not affect ad libitum feeding in lean mice; however, both doses acutely reduced high-fat diet intake in obese mice. While 5 mg/kg had no effect on hunger-induced feeding, 12 mg/kg suppressed refeeding in both chow- and high-fat-fed mice of both sexes and reduced weight regain in obese mice. These findings identify SBI-553 as a potential strategy for reducing food intake and supporting weight loss.
ER -