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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
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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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 1

The effects of SG or sham surgery on female mice before and during pregnancy.

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The effects of SG or sham surgery on female mice before and during pregn...
(A and B) Mice weight and blood glucose measured at 7 am in the month after SG. (C and D) Glucose levels and AUC following an oral glucose tolerance test. (E) Mice weight at E18.5. (F and G) Nonfasting and fasting blood glucose during pregnancy. (H–J) Fasting levels of BCAA, insulin, and glucagon at E18.5. (K) Glp1 levels 10 minutes after gavage at E18.5. Blue: sham-operated mice; red: SG-operated mice. In A–D, sham-operated mice n = 28, SG-operated mice n = 25; in E–G, sham-operated mice n = 11, SG-operated mice n = 10; in H–J, sham-operated mice n = 5, SG-operated mice n = 5; in K, sham-operated mice n = 7, SG-operated mice n = 4. *P < 0.05, **P < 0.01 by 2-way continuous measure ANOVA for A–C, by 2-tailed Student’s t test for D–I; and by Mann-Whitney nonparametric U test for J and K.

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