Bourreau, J. | bioRxiv Science

bioRxiv2024

Vertical sleeve gastrectomy in rodents: impact on metabolic, cardiovascular and hepatic functions of mothers and perinatal consequences

BackgroundMaternal obesity is a well-known risk factor for obstetrical complications during pregnancy, and cardiovascular and metabolic pathologies in the offspring. In the last two decades, bariatric surgery has emerged as the most effective treatment for severe obesity, and is known to improve fertility, leading to a rise in procedures among women of childbearing age. ObjectivesThis study investigates the impact of pre-conceptional sleeve gastrectomy (SG) on metabolic, cardiovascular and hepatic functions of mothers at short and middle terms after surgery, and its perinatal consequences. MethodsSprague-Dawley female control rats (CM) received a standard diet, while others were fed a high-fat, high-sugar diet (HFHS). HFHS rats were divided into obese mothers (OM) and sleeve gastrectomy mothers (SM). One month after surgery, all groups underwent gestation and subsequent lactation Metabolic function was assessed at 1 and 4 months after surgery; cardiovascular and hepatic functions were evaluated only 4 months after SG. ResultsFrom 1 month post-surgery, SM showed normalized leptin and insulin levels compared to OM. Moreover, SG normalized body weight associated with a decreased white adipose tissue weight and adipocyte size at 4 months post-surgery. Interestingly, although steatosis has been detected in HFHS rats, SM exhibited only hepatic fibrosis at 4 months post-surgery. Moreover, SM showed a hypertrophic remodeling of thoracic aorta without effect on its vasoreactivity but along with endothelial dysfunction of mesenteric artery, associated with a stronger involvement of COX/PGI2 pathway. In the offspring, obesity in mothers was associated to a decreased liter size, reversed by sleeve gastrectomy without any effect on the birth weight of pups. ConclusionWhile this study reports an improvement of metabolic function at short- and medium-terms after bariatric surgery, our results highlight an alteration of hepatic and vascular functions by sleeve gastrectomy, with minimal effect on the offspring in the perinatal period.

physiology↗

bioRxiv2023

Adaptive remodeling of rat adrenomedullary stimulus-secretion coupling in response to a chronic hypertensive environment

Chronic elevated blood pressure impinges on the functioning of multiple organs and therefore harms body homeostasis. Elucidating the protective mechanisms whereby the organism copes with sustained or repetitive blood pressure rises is therefore a topical challenge. Here we address this issue in the adrenal medulla, the master neuroendocrine tissue involved in the secretion of catecholamines, influential hormones in blood pressure regulation. Using acute adrenal slices from spontaneously hypertensive rats, we show that chromaffin cell stimulus-secretion coupling is remodeled, resulting in a less efficient secretory function primarily upon sustained electrical or cholinergic challenges. The remodeling is supported by revamped cellular and tissular mechanisms, including chromaffin cell excitability through voltage-gated ion channel expression changes, gap junctional communication and cholinergic synaptic transmission. As such, by weakening its competence to release catecholamines, the hypertensive medulla has elaborated an adaptive shielding mechanism against damaging effects of redundant elevated catecholamine secretion and associated blood pressure.

physiology↗