Maternal antagonism of Glp1 reverses the adverse outcomes of sleeve gastrectomy on mouse offspring

Liron Hefetz, Rachel Ben-Haroush Schyr, Michael Bergel, Yhara Arad, Doron Kleiman, Hadar Israeli, Itia Samuel, Shira Azulai, Arnon Haran, Yovel Levy, Dana Sender, Amihai Rottenstreich, Danny Ben-Zvi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Mothers that underwent bariatric surgery are at higher risk for delivering a small-for-gestational age (SGA) infant. This phenomenon is attributed to malabsorption and rapid weight loss following surgery. We compared pregnancy outcomes in lean mice that underwent sham surgery or sleeve gastrectomy (SG). SG led to a reduction in glucose levels and an increase in postprandial levels of glucagon-like peptide 1 (Glp1) without affecting mice weight during pregnancy. Pups of SGoperated mice (SG pups) were born SGA. The placenta and pancreas of the pups were not affected by SG, although a high-fat diet caused hepatic steatosis and glucose intolerance in male SG pups. Treatment with a Glp1 receptor antagonist during pregnancy normalized the birth weight of SG pups and diminished the adverse response to a high-fat diet without affecting glucose levels of pregnant mice. The antagonist did not affect the birth weight of pups of sham-operated mice. Our findings link elevated Glp1 signaling, rather than weight loss, to the increased prevalence of SGA births following bariatric surgery with metabolic consequences for the offspring. The long-term effects of bariatric surgery on the metabolic health of offspring of patients require further investigation.

Original languageAmerican English
Article numbere156424
JournalJCI insight
Issue number7
StatePublished - 8 Apr 2022

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© 2022, Hefetz et al.


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