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Maternal antagonism of Glp1 reverses the adverse outcomes of sleeve gastrectomy on mouse offspring
Liron Hefetz, … , Amihai Rottenstreich, Danny Ben-Zvi
Liron Hefetz, … , Amihai Rottenstreich, Danny Ben-Zvi
Published April 8, 2022
Citation Information: JCI Insight. 2022;7(7):e156424. https://doi.org/10.1172/jci.insight.156424.
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Research Article Metabolism

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

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Abstract

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 SG-operated 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.

Authors

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

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Figure 6

The long-term effects of SG on male offspring are reversed by maternal treatment with Exendin 9-39.

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The long-term effects of SG on male offspring are reversed by maternal t...
(A and B) Weight and nonfasting glucose levels of male offspring of sham- or SG-operated mice treated or untreated with Exendin 9-39 during pregnancy. The dashed black line denotes a switch from normal chow to a high-fat high-sucrose diet. (C–F) Oral glucose tolerance test, AUC, fasting glucose, and insulin levels at week 15 of the 4 experimental groups. (G) Representative H&E staining of the liver of the 4 experimental groups. (H) Histological grade of hepatic steatosis in the 4 experimental groups. Blue: male offspring of sham-operated mice untreated with Exendin 9-39 during pregnancy (full) or treated with Exendin 9-39 (dashed); Red: male offspring of sham-operated mice untreated with Exendin 9-39 during pregnancy (full) or treated with Exendin 9-39 (dashed). *P < 0.05, **P < 0.01 by 2-way ANOVA with Tukey HSD post hoc test in D, F, H, and I or by 3-way continuous measures ANOVA in A–C and E. All panels sham Ex9– n = 7, sham Ex9+ n = 7, SG Ex9– n = 7, SG Ex9+ n = 6. *P < 0.05, **P < 0.01 for the comparison between sham-Ex9– and SG-Ex9-. †P < 0.05, ††P < 0.01 for the comparison between SG-Ex9– and SG-Ex9+. ‡P < 0.05, ‡‡P < 0.01 for the comparison between sham-Ex9– and sham-Ex9+.

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