Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
J Nutr. 2021 Jun 1;151(6):1487-1496. doi: 10.1093/jn/nxab026.
Exposure to a maternal high-fat diet (HFD) predisposes offspring to nonalcoholic fatty liver disease.
The aim of this study was to explore whether milk fat globule membrane (MFGM) supplementation during suckling exerts a long-term protective effect on hepatic lipid metabolism in adult offspring exposed to maternal HFD.
We fed 5-week-old female C57BL/6J mice either a HFD (60% kcal fat) or control diet (CD; 16.7% kcal fat) for 3 weeks before mating, as well as throughout gestation and lactation. After delivery, male offspring from HFD dams were supplemented with 1 g/(kg body weight·day) MFGM (HFD + MFGM group) or the same volume of vehicle (HFD group) during suckling. Male offspring from CD dams were also supplemented with vehicle during suckling (CD group). All offspring were weaned onto CD for 8 weeks. Histopathology, metabolic parameters, lipogenic level, oxidative stress, and mitochondria function in the liver were analyzed. A 1-way ANOVA and a Kruskal-Wallis test were used for multi-group comparisons.
As compared to the CD group, the HFD group had more lipid droplets in livers, and exhibited ∼100% higher serum triglycerides, ∼38% higher hepatic triglycerides, ∼75% higher serum aspartate aminotransferase, and ∼130% higher fasting blood glucose (P < 0.05). The changes of these metabolic parameters were normalized in the HFD + MFGM group. Phosphorylated mammalian targets of rapamycin and AKT were downregulated, but phosphorylated adenosine monophosphate-activated protein kinase was upregulated in the HFD + MFGM group as compared to the HFD group (P < 0.05). As compared to the CD group, the HFD group showed an ∼80% higher malondialdehyde level, and ∼20% lower superoxide dismutase activity (P < 0.05), which were normalized in the HFD + MFGM group. Additionally, mitochondria function was also impaired in the HFD group and normalized in the HFD + MFGM group.
MFGM supplementation during suckling ameliorates maternal HFD-induced hepatic steatosis in mice via suppressing de novo lipogenesis, reinforcing antioxidant defenses and improving mitochondrial function.
暴露于母体高脂肪饮食（HFD）会使后代易患非酒精性脂肪肝疾病。
本研究旨在探讨哺乳期补充乳脂肪球膜（MFGM）是否对暴露于母体 HFD 的成年后代的肝脂质代谢产生长期保护作用。
我们在交配前用 HFD（60%卡路里脂肪）或对照饮食（CD；16.7%卡路里脂肪）喂养 5 周龄的 C57BL/6J 雌性小鼠 3 周，并在整个妊娠期和哺乳期喂食。分娩后，HFD 母鼠的雄性后代在哺乳期补充 1g/（kg 体重·天）MFGM（HFD+MFGM 组）或相同体积的载体（HFD 组）。CD 母鼠的雄性后代也在哺乳期补充载体（CD 组）。所有后代均在断奶后 8 周内转为 CD 饮食。分析肝脏的组织病理学、代谢参数、脂肪生成水平、氧化应激和线粒体功能。采用单因素方差分析和 Kruskal-Wallis 检验进行多组比较。
与 CD 组相比，HFD 组肝脏中的脂滴更多，血清甘油三酯高约 100%，肝甘油三酯高约 38%，血清天冬氨酸氨基转移酶高约 75%，空腹血糖高约 130%（P < 0.05）。这些代谢参数的变化在 HFD+MFGM 组中得到了正常化。与 HFD 组相比，HFD+MFGM 组磷酸化哺乳动物雷帕霉素靶蛋白和 AKT 下调，但磷酸化腺苷单磷酸激活蛋白激酶上调（P < 0.05）。与 CD 组相比，HFD 组丙二醛水平高约 80%，超氧化物歧化酶活性低约 20%（P < 0.05），在 HFD+MFGM 组中得到了正常化。此外，HFD 组的线粒体功能也受损，在 HFD+MFGM 组中得到了正常化。
哺乳期补充 MFGM 通过抑制从头脂肪生成、增强抗氧化防御和改善线粒体功能，改善了母鼠高脂肪饮食诱导的肝脂肪变性。
