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

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.

SUBMITTER: Hefetz L

PROVIDER: S-EPMC9057621 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Hefetz Liron L Ben-Haroush Schyr Rachel R Bergel Michael M Arad Yhara Y Kleiman Doron D Israeli Hadar H Samuel Itia I Azulai Shira S Haran Arnon A Levy Yovel Y Sender Dana D Rottenstreich Amihai A Ben-Zvi Danny D

JCI insight 20220408 7

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) ...[more]

PMID: 35393955

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Project description:BackgroundPregnancies occurring after bariatric surgery are associated with various perinatal complications. However, there may be differences in the type of perinatal complications occurring after different methods of bariatric surgery. The aim of the current study was to compare adverse perinatal outcomes in pregnant women following Roux-en-Y Gastric Bypass (RYGB) vs. Sleeve Gastrectomy (SG).MethodsA systematic database search was performed in PubMed, Embase, Scopus and CINAHL. Observational studies comparing perinatal outcomes post-bariatric (RYGB and SG) surgery to pregnancies without prior surgery were selected. Outcomes of interest were: maternal body mass index (BMI) at the time of conception, mode of delivery, time from surgery to conception, birth weight, gestational age and intrauterine fetal death. Article selection, risk of bias assessment and data extraction, were performed by two authors. The study protocol was published in its revised form in PROSPERO, registration number: CRD42021234480.ResultsA total of 3201 records were extracted. After duplicates were removed, 3143 records were screened for inclusion. Six studies fitted the selection criteria, of which four studies were RYGB and two SG (1100 post-RYGB vs. 209 post-SG). For the included studies, higher incidence of both SGA (22.9%, 11.9%, 14.2%) and LGA (4.2%, 4.8%, 1.7%) in SG compared to Roux-en-Y (SGA: 8.8%, 7.7%, 11.5%, 8.3% and LGA: 3.4%, 0.7%) were observed. SG had a shorter surgery to conception interval as compared to RYGB. Risk of bias assessment was moderate to serious for the studies included in the review, with bias in selection of participants being the major reason.ConclusionOur systematic review demonstrated no major differences in BMI, mode of delivery, birthweight, gestational age, or rates of intrauterine death between women having undergone RYGB vs. SG. The rate of SGA and LGA births were higher in the SG group, but this group also had a shorter surgery to conception interval. Future studies are indicated to counsel women of reproductive age on the most appropriate type of bariatric surgery that is associated with the best perinatal outcomes.

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

Publications

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

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