Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil.
Life Sci. 2022 Oct 15;307:120873. doi: 10.1016/j.lfs.2022.120873. Epub 2022 Aug 8.
Perinatal maternal hypercaloric diets increase the susceptibility to metabolic disorders in the offspring. We hypothesized that maternal intake of an isocaloric moderate-fat diet (mMFD) would disturb the glucose homeostasis and favor the β-cell failure in response to fructose overload in adult male offspring.
Female Wistar rats received an isocaloric diet (3.9 kcal/g) containing 29 % (mMFD) or 9 % as fat (mSTD) prior mating and throughout gestation and lactation. After weaning, male offspring received standard chow and fructose-drinking water (15 %) between 120 and 150 days old.
mMFD offspring had higher body weight, visceral adiposity and, fasting glycemia, with normal insulinemia. Fructose increased glycemia at 15 min from oral glucose administration, but only mMFD had returned to basal glucose levels at 120 min. Fructose increased HOMA-IR index regardless diet, but only mMFD exhibited hyperinsulinemia and a higher HOMA-β index. mMFD pancreatic islets showed increased area and insulin immunostaining density, suggesting β-cell hypertrophy. Fructose induced the expected compensatory hypertrophy in mSTD islets, while the opposite occurred in mMFD islets, associated with reduced insulin immunostaining, suggesting lower insulin storage. Pancreatic islets isolated from mMFD offspring exhibited higher glucose-stimulated insulin release at physiological concentrations. However, at higher glucose concentrations, the islets from fructose-treated mMFD reduced dramatically their insulin release, suggesting exhaustion.
Isocaloric mMFD induced adaptive mechanism in the offspring allowing insulin hypersecretion, but under metabolic challenge with fructose, β-cell compensation shifts to exhaustion, favoring dysfunction. Therefore, a maternal MFD may contribute to developing diabetes under fructose overload in the adult offspring.
围产期母体高卡路里饮食会增加后代代谢紊乱的易感性。我们假设，母体摄入等热量的中脂肪饮食（mMFD）会干扰葡萄糖稳态，并使成年雄性后代果糖过载时β细胞衰竭。
雌性 Wistar 大鼠在交配前和整个妊娠期及哺乳期接受含 29%（mMFD）或 9%脂肪（mSTD）的等热量饮食。断奶后，雄性后代在 120-150 天龄时接受标准饲料和果糖饮用水（15%）。
mMFD 后代体重、内脏脂肪和空腹血糖升高，但胰岛素正常。果糖在口服葡萄糖后 15 分钟增加血糖，但只有 mMFD 在 120 分钟后恢复基础血糖水平。果糖增加 HOMA-IR 指数，但无论饮食如何，只有 mMFD 表现出高胰岛素血症和更高的 HOMA-β 指数。mMFD 胰岛显示出面积和胰岛素免疫染色密度增加，提示β细胞肥大。果糖诱导 mSTD 胰岛发生预期的代偿性肥大，而 mMFD 胰岛则相反，胰岛素免疫染色减少，提示胰岛素储存减少。从 mMFD 后代分离的胰岛在生理浓度下表现出更高的葡萄糖刺激胰岛素释放。然而，在更高的葡萄糖浓度下，果糖处理的 mMFD 胰岛的胰岛素释放显著减少，表明衰竭。
等热量 mMFD 诱导后代适应性机制，允许胰岛素分泌过多，但在果糖代谢挑战下，β细胞代偿转向衰竭，促进功能障碍。因此，母体 MFD 可能会导致成年后代果糖过载时发生糖尿病。
