GIPR-Ab/GLP-1 peptide–antibody conjugate requires brain GIPR and GLP-1R for additive weight loss in obese mice

Apr 29, 2025Nature metabolism

Combined activation of brain GIP and GLP-1 receptors helps reduce weight in obese mice

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Abstract

A peptide-antibody conjugate that blocks while activating is essential for maximal weight loss in obese mice.

  • CNS GIPR and GLP-1R are both necessary for achieving the full weight loss benefits of the GIPR-Ab/GLP-1 treatment.
  • Dulaglutide leads to greater weight loss in mice lacking CNS GIPR compared to those with it.
  • The combination of dulaglutide and GIPR-Ab results in reduced weight loss in CNS GIPR knockout mice.
  • Mice treated with GIPR-Ab/GLP-1 and CNS GIPR knockout mice show similar changes in gene expression related to fat tissue and liver function.
  • Activation of specific brain regions related to appetite regulation occurs with the GIPR-Ab/GLP-1 treatment.

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Key numbers

31.9%
Weight Loss Percentage
Average weight loss observed by day 18 in treated mice.
19.4%
Body Weight Change in Female Mice
Percentage weight loss in female mice treated with .

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