MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
Eur J Nutr. 2020 Jun;59(4):1707-1716. doi: 10.1007/s00394-019-02025-1. Epub 2019 Jun 14.
Excessive exposure of glucocorticoids activates adipose lipolysis, increases circulating free fatty acids, and contributes to ectopic lipid deposition in liver and skeletal muscle. Our previous study demonstrated that maternal betaine supplementation attenuates glucocorticoid-induced hepatic lipid accumulation in rat offspring. However, it is unclear whether maternal betaine supplementation is effective in preventing glucocorticoid-induced lipolysis in the adipose tissue of offspring.
In this study, 20 pregnant rats were fed with basal or betaine-supplemented (10 g/kg) diets throughout gestation and lactation, and the offspring rats were raised on the basal diet from weaning till 3 months of age followed by daily intraperitoneal injection of saline or 0.1 mg/kg dexamethasone (DEX) for 3 weeks.
Chronic DEX treatment significantly (P < 0.05) decreased serum corticosterone level and increased proinflammatory cytokines, such as TNFα, IL-1β, and IL-6. Meanwhile, GR protein content in adipose tissue was increased in response to DEX treatment, which was associated with a significant (P < 0.05) up-regulation of ATGL and HSL expression at both mRNA and protein levels. All these DEX-induced changes were significantly (P < 0.05) attenuated in progeny rats derived from betaine-supplemented dams. Furthermore, DEX-induced hypomethylation of ATGL and HSL gene promoters was reversed by maternal betaine supplementation.
Taken together, these results suggest that maternal betaine supplementation is effective in alleviating glucocorticoid-induced lipolysis in adipose tissue with modification of DNA methylation on the promoter of lipolytic genes.
糖皮质激素过度暴露会激活脂肪分解，增加循环游离脂肪酸，并导致肝脏和骨骼肌的异位脂质沉积。我们之前的研究表明，母体甜菜碱补充可减轻糖皮质激素诱导的大鼠子代肝脏脂质堆积。然而，母体甜菜碱补充是否能有效预防糖皮质激素诱导的子代脂肪组织脂肪分解尚不清楚。
在这项研究中，20 只怀孕大鼠在整个妊娠期和哺乳期均接受基础或甜菜碱补充（10 g/kg）饮食喂养，子代大鼠在断奶后继续接受基础饮食喂养，直至 3 个月大，然后每天腹腔注射生理盐水或 0.1 mg/kg 地塞米松（DEX）3 周。
慢性 DEX 处理显著（P<0.05）降低了血清皮质酮水平，并增加了促炎细胞因子，如 TNFα、IL-1β 和 IL-6。同时，DEX 处理后脂肪组织中的 GR 蛋白含量增加，这与 ATGL 和 HSL 的表达在 mRNA 和蛋白水平上的显著（P<0.05）上调有关。母鼠补充甜菜碱可显著（P<0.05）减轻这些 DEX 诱导的变化。此外，DEX 诱导的 ATGL 和 HSL 基因启动子低甲基化也被母鼠甜菜碱补充所逆转。
综上所述，这些结果表明，母体甜菜碱补充可有效缓解糖皮质激素诱导的脂肪分解，同时改变脂肪分解基因启动子上的 DNA 甲基化。
