Deer Evangeline M, Phillips Charles L, Welch Bradley A, Himel Alexandra R, Duncan Brittany C, Spann Redin A, Grayson Bernadette E
Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Curr Res Physiol. 2020 Dec;3:50-58. doi: 10.1016/j.crphys.2020.11.002. Epub 2020 Dec 8.
Bariatric surgery produces significant positive benefits to recipients such as significant body fat loss and resolution of the various obesity-related comorbidities, such as reduced reproductive function. Females of childbearing age seek bariatric surgical remedies to improve their chance of successful pregnancy; however, limited knowledge exists on the impact of surgical weight loss to subsequently born offspring. We previously reported that circulating leptin levels were reduced in pregnant females having previously received vertical sleeve gastrectomy (VSG) in comparison to control dams having received Sham surgery. Furthermore, the levels of leptin receptors in the VSG placenta were also reduced in VSG. These data suggest a significant difference in leptin signaling during pregnancy that may produce an altered developmental environment for the offspring. Here, we investigate the adult offspring of dams having received VSG or Sham-VSG prior to pregnancy. Endogenous fasting plasma leptin levels were not different between Sham and VSG offspring. Fasting leptin receptor mRNA in the medial basal hypothalamus (MBH) was elevated in VSG offspring in comparison to Sham. Intraperitoneal administration of exogenous leptin produced reductions in acute food intake in male Sham offspring, but did not reduce food intake at any time point measured in male VSG offspring. Using Western blot, we identified elevated and ratios in the MBH of post-VSG offspring in comparison to controls. Using immunohistochemistry, we found an increased number of positive cells in the arcuate nucleus in the Sham offspring in comparison to VSG. In contrast, within the paraventricular and ventromedial nuclei in the hypothalamus of the VSG offspring had elevated numbers of -positive cells in comparison to controls. Collectively, these data support our hypothesis that leptin signaling is dysregulated in VSG offspring and may be partially responsible for the long-term impact of maternal bariatric surgery on the metabolic health of offspring.
减肥手术给接受者带来了显著的积极益处，比如大量体脂减少以及各种与肥胖相关的合并症得到缓解，如生殖功能减退。育龄女性寻求减肥手术治疗以提高成功怀孕的几率；然而，关于手术减肥对随后出生后代的影响，目前了解有限。我们之前报道过，与接受假手术的对照母鼠相比，先前接受垂直袖状胃切除术（VSG）的怀孕母鼠循环瘦素水平降低。此外，VSG组胎盘的瘦素受体水平也降低。这些数据表明孕期瘦素信号存在显著差异，这可能会为后代产生改变的发育环境。在此，我们研究怀孕前接受VSG或假VSG手术的母鼠的成年后代。假手术组和VSG组后代的内源性空腹血浆瘦素水平没有差异。与假手术组相比，VSG组后代内侧基底下丘脑（MBH）中的空腹瘦素受体mRNA升高。对雄性假手术组后代腹腔注射外源性瘦素可使急性食物摄入量减少，但在测量的任何时间点，对雄性VSG组后代的食物摄入量均无减少作用。使用蛋白质印迹法，我们发现与对照组相比，VSG组后代MBH中的 和 比率升高。使用免疫组织化学方法，我们发现与VSG组相比，假手术组后代弓状核中 阳性细胞数量增加。相反，与对照组相比，VSG组后代下丘脑室旁核和腹内侧核内 阳性细胞数量增加。总体而言，这些数据支持了我们的假设，即VSG组后代的瘦素信号失调，这可能部分导致了母体减肥手术对后代代谢健康的长期影响。
