Problem: Exposures during the perinatal period, a phase of rapid development and growth, may have a profound and sustained effect on metabolic disturbances later in life. The pro-inflammatory advanced glycation end products (AGEs) are widely consumed in the Western diet. The purpose of this study was to determine whether perinatal exposure to these dietary AGEs alters metabolic parameters, in particular adiposity and glucose hemostasis, in male mice offspring.

Methods: Seven-week-old female CD1 mice were placed before mating and then throughout pregnancy and lactation on either a low AGE (L-AGE; n = 13) or high AGE (H-AGE; n = 13) diet. All offspring in both groups were weaned postnatal day 21 onto normal diet and studied through to 21 weeks of age. The offspring were counted and weighed weekly, starting at birth until 21 weeks of age, to assess the growth curve. At the time of sacrifice, Echo MRI was performed to measure adiposity and to record liver, white epididymal adipose tissue (WAT), and inguinal fat weights. Serum levels of leptin as well as insulin and glucose tolerance tests (ITT and GTT) were compared.

Results: The Body weight at birth of offspring of dams that were on H-AGE diet was significantly lower compared to the body weight of offspring of dams that were on L-AGE diet. Echo MRI data showed that the offspring of dams that were H-AGE diet had significantly lower fat mass, lower epididymal WAT fat weight, and lower inguinal fat weight but higher lean body mass and similar liver weight. They also had significantly higher glucose levels during GTT and ITT, as well as significantly lower serum leptin levels compared to the offspring of dams that were on the L-AGE diet.

Conclusions: These results indicate that perinatal exposure to a maternal diet elevated in AGEs causes deficits in perinatal growth and impairment in glucose hemostasis in male mice. These findings suggest that AGEs may represent an important new class of mediators of adiposity and the metabolic syndrome.

Keywords: adiposity; advanced glycation end products; glucose; homeostasis.

© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

问题： 孕期暴露于快速发育和生长阶段，可能会对生命后期的代谢紊乱产生深远而持久的影响。晚期糖基化终末产物（AGEs）在西方饮食中广泛存在，并具有促炎作用。本研究旨在确定孕期摄入这些膳食AGEs是否会影响雄性小鼠后代的代谢参数，特别是脂肪堆积和血糖稳态。

方法： 七周大的雌性CD1小鼠在接受交配前以及怀孕和哺乳期间被分为两组，分别食用低AGE（L-AGE；n = 13）或高AGE（H-AGE；n = 13）饮食。所有后代在21天断奶后换为正常饮食，并研究至21周龄。从出生到21周龄期间每周对小鼠进行计数和称重，以评估生长曲线。在牺牲时进行了Echo MRI扫描来测量脂肪量并记录肝脏、白色附睾脂肪组织（WAT）和腹股沟脂肪的重量。比较了血清瘦素水平以及胰岛素耐受试验（ITT）和葡萄糖耐受试验（GTT）的结果。

结果： 与食用低AGE饮食的小鼠后代相比，食用高AGE饮食的母亲所生小鼠在出生时体重显著较低。Echo MRI数据显示，这些小鼠的脂肪量、附睾WAT脂肪重量和腹股沟脂肪重量均显著降低，但瘦体重增加且肝脏重量相似。它们还在葡萄糖耐受试验（GTT）和胰岛素耐受试验（ITT）中表现出更高的血糖水平，并且血清瘦素水平显著低于食用低AGE饮食的小鼠后代。

结论： 这些结果表明，孕期暴露于高AGEs的母鼠会导致雄性小鼠幼崽生长发育迟缓和糖代谢障碍。这提示AGEs可能代表了肥胖症和代谢综合征的重要新一类介质。

关键词： 脂肪堆积；晚期糖基化终末产物；葡萄糖；稳态