Dysregulated appetitive leptin signaling in male rodent offspring from post-bariatric dams

Deer, Evangeline; Phillips, Charles L.; Welch, Bradley A.; Himel, Alexandra R; Duncan, Brittany; Spann, Redin A.; Grayson, Bernadette E.

doi:10.1016/j.crphys.2020.11.002

Cited by 5 publications

(10 citation statements)

References 38 publications

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“…Finally, as mentioned, prepregnancy weight loss is accompanied by a higher likelihood of excessive GWG, which has been associated with impaired insulin sensitivity and beta‐cell function 46–48 . Beyond GWG, animal models have also revealed that prepregnancy weight loss results in structural and biological alterations in the placenta (e.g., reduced weight, increased inflammation, dysregulated leptin signaling) 49–51 . Considering that the placenta plays a crucial role in glucose regulation in pregnancy, the disruptions in its structure and function may affect insulin sensitivity thus modifying the metabolic effect of pregnancy weight loss.…”

Section: Discussionmentioning

confidence: 99%

Prepregnancy weight loss and maternal metabolic and inflammatory biomarkers during pregnancy: An analysis of National Health and Nutrition Examination Survey

Yu,

Ma,

Groth

2024

J of Obstet and Gynaecol

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AimWomen with overweight or obesity are recommended to lose weight before conception to optimize pregnancy outcomes. However, the obstetrical implications of prepregnancy weight loss have been minimally examined. The objective of this study was to investigate the association between prepregnancy weight loss and maternal metabolic and inflammatory profiles during a subsequent pregnancy.MethodsThis study was a retrospective analysis of National Health and Nutrition Examination Survey data (2003–2018). Participants were women who were pregnant at the time of assessment. Prepregnancy weight loss was described as percent weight change based on self‐reported baseline (1 year before pregnancy) and prepregnancy weight. Metabolic (e.g., blood pressure [BP]) and inflammatory biomarkers (i.e., high‐sensitivity C‐reactive protein [hs‐CRP]) were determined by standard medical tests. Statistical analyses included linear regressions with appropriate imputation, weighting, and variance estimation techniques.ResultsParticipants (N = 236) reported a mean percent weight loss of 4.6% (standard error [SE] = 0.3%) during the year before pregnancy. Regression models showed that prepregnancy weight loss was inversely associated with levels of total cholesterol (β = −1.24, p = 0.01), low‐density lipoprotein‐cholesterol (β = −0.79, p < 0.01), and high‐density lipoprotein‐cholesterol (β = −0.18, p < 0.01). The effect of prepregnancy weight loss on BP, insulin sensitivity, and hs‐CRP was not significant, although there was a trend toward higher levels of diastolic BP (β = 0.24, p = 0.07) and hs‐CRP (β = 0.10, p = 0.08).ConclusionsThis study found favorable changes in lipid profiles following prepregnancy weight loss. Due to limitations such as a relatively small sample size, self‐reported weight measures, and missing data on several outcome variables, future studies are needed to confirm study findings.

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Section: Discussionmentioning

confidence: 99%

Prepregnancy weight loss and maternal metabolic and inflammatory biomarkers during pregnancy: An analysis of National Health and Nutrition Examination Survey

Yu,

Ma,

Groth

2024

J of Obstet and Gynaecol

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“…The rats were subsequently separated into two weight-matched groups: sham, N = 20, and VSG, N = 24. These bariatric animals were previously well characterized [ 26 , 27 ] and were used to generate the female offspring who were subjects used in this study.…”

Section: Methodsmentioning

confidence: 99%

“…Animal care was performed as previously described [ 22 , 25 , 26 , 27 ]. Briefly, animals were maintained on Osmolite OneCal liquid diet (Abbott Laboratories, North Chicago, IL, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Animals received 5 ml of 0.9% saline daily with buprenorphine and carprofen for pain management for three days. Animals were weight-stabilized for six weeks before mating, as previously described [ 22 , 25 , 26 , 27 ].…”

Section: Methodsmentioning

confidence: 99%

“…We have described macronutrient and hormone differences in the milk produced by dams with previous VSG surgery compared to controls [ 24 ]. Both ghrelin [ 25 ] and leptin [ 26 ] signaling are dysregulated in the offspring of dams with bariatric surgery prior to pregnancy. Further, VSG offspring exhibit profound changes to their immune systems as a result of being born to dams that have lost weight through bariatric means [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Altered Estrous Cyclicity and Feeding Neurocircuitry, but Not Cardiovascular Indices in Female Offspring from Dams with Previous Vertical Sleeve Gastrectomy Surgery

Johnson,

Welch,

Aravindan

et al. 2023

Brain Sciences

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Metabolic syndrome (MetS), which includes obesity, diabetes, hypertension, hyperlipidemia, and fatty-liver disease, affects more than two-thirds of the U.S. population. Surgical weight loss has been popularized in the last several decades as a means to produce significant weight loss and improvements in the comorbidities of MetS. Women are by far the most common recipients of these surgeries (more than 85%). Women of childbearing age are very likely to pursue surgical weight loss to improve their reproductive function and fertility for childbearing purposes. Significant research using pre-clinical models from our laboratory and clinical data from around the world suggest that surgical weight loss before pregnancy may have negative consequences for offspring. The present study investigates the metabolic endpoints in female-rodent offspring born to dams who had previously received vertical sleeve gastrectomy (VSG) before pregnancy. Comparisons were made to offspring from lean and obese dams. In the adult offspring of either maternal VSG or sham surgery, no differences in body weight, body fat, or lean body mass between groups were identified. The blood pressure measured in a subset of female offspring showed no differences between the VSG and the sham groups. Estrus cyclicity measured by lavage on serial days showed altered cycles in the VSG offspring compared to the controls. For animals that had previously only been exposed to chow, rats were fasted overnight and then given a 1 g meal of either chow or a novel high-fat diet (HFD). The animals were euthanized and paraformaldehyde (PFA)-perfused to perform brain immunohistochemistry for c-Fos, an immediate–early gene activated by novel stimuli. In the VSG rats exposed to either the chow or the HFD meal, the c-Fos-activated cells were significantly blunted in the nucleus of the solitary tract (p < 0.05), the paraventricular nucleus of the hypothalamus (PVN) (p < 0.05), and the dorsal medial nucleus of the hypothalamus (DMH) (p < 0.05) in comparison to the sham controls. These data suggest that the hypothalamic wiring within the brain that controls the response to nutrients and reproductive function was significantly altered in the VSG offspring compared to the offspring of the dams that did not receive weight-loss surgery.

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The association of higher offspring early‐childhood weight gain with prepregnancy metabolic and bariatric surgery

Hilaire,

Babcock,

White

et al. 2024

Obesity

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ObjectiveThe objective of this study was to assess maternal gestational outcomes and offspring growth trajectories following prepregnancy metabolic and bariatric surgery (MBS) compared with non‐MBS controls.MethodsSingle‐center deliveries between January 2020 and March 2023 with prepregnancy Roux‐en‐Y gastric bypass (herein referred to as “bypass”), sleeve gastrectomy (herein referred to as “sleeve”), and non‐MBS controls were included. Offspring growth trajectories were compared with the World Health Organization child growth standards. Linear mixed models assessed MBS‐bypass and MBS‐sleeve offspring weight, length, and BMI trajectories with a prepregnancy BMI 27 to 37 kg/m2 and propensity score‐matched controls.ResultsThe study included 440 participants with prepregnancy MBS (MBS‐bypass, 185; MBS‐sleeve, 225; 76% Hispanic/Latino) and 13,434 non‐MBS controls. Gestational weight gain and gestational diabetes mellitus were similar, whereas hypertensive disorders of pregnancy were more common after MBS. The post‐MBS offspring had lower birth weight but higher weight gain at 24 months (sleeve, +1.4 kg [95% CI: 1.0–1.9]; bypass, +0.5–0.7 kg [95% CI: 0.0–1.2]) compared with non‐MBS groups. Male children had higher weight gain than females. The post‐MBS‐sleeve but not the post‐MBS‐bypass offspring had higher BMI z scores.ConclusionsThe higher early‐life weight gain and sex differences in the post‐MBS‐sleeve group compared with the post‐MBS‐bypass group provide a window toward elucidating pathways to mitigate intergenerational metabolic risk transfer.image

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Dysregulated appetitive leptin signaling in male rodent offspring from post-bariatric dams

Cited by 5 publications

References 38 publications

Prepregnancy weight loss and maternal metabolic and inflammatory biomarkers during pregnancy: An analysis of National Health and Nutrition Examination Survey

Prepregnancy weight loss and maternal metabolic and inflammatory biomarkers during pregnancy: An analysis of National Health and Nutrition Examination Survey

Altered Estrous Cyclicity and Feeding Neurocircuitry, but Not Cardiovascular Indices in Female Offspring from Dams with Previous Vertical Sleeve Gastrectomy Surgery

The association of higher offspring early‐childhood weight gain with prepregnancy metabolic and bariatric surgery

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