Maternal and post-weaning high-fat, high-sucrose diet modulates glucose homeostasis and hypothalamic POMC promoter methylation in mouse offspring.
Substantial evidence demonstrated that maternal dietary nutrients can significantly determine the susceptibility to developing metabolic disorders in the offspring. Therefore, we aimed to investigate the later-life effects of maternal and postweaning diets interaction on epigenetic modification of the central nervous system in the offspring. We examined the effects of dams fed a high-fat, high-sucrose (FS) diet during pregnancy and lactation and weaned to FS diet continuously until 32 weeks of age. Then, DNA methylation and gene expressions of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in the offspring. Offspring of FS diet had heavier body weight, impaired glucose tolerance, decreased insulin sensitivity and higher serum leptin level at 32-week age (p < 0.05). The expression of POMC and MC4R genes were significantly increased in offspring exposed to FS diet during gestation, lactation and into 32-week age (p < 0.05). Consistently, hypomethylation of POMC promoter in the hypothalamus occurred in the FS diet offspring (p < 0.05), compared with the C group. However, no methylation was detected of MC4R promoter in both the two groups. Furthermore, POMC-specific methylation (%) was negatively associated with glucose response to a glucose load (r = -0.273, p = 0.039). Maternal and post-weaning high-fat diet predisposes the offspring for obesity, glucose intolerance and insulin resistance in later life. Our findings can advance our thinking around the DNA methylation status of the promoter of the POMC and MC4R genes between long-term high-fat, high-sucrose diet and glucose homeostasis in mouse.
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Diabetes Research Center of Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, People's Republic of China.
Jia
J
Zheng
Xinhua
X
Xiao
Qian
Q
Zhang
Miao
M
Yu
Jianping
J
Xu
Zhixin
Z
Wang
Cuijuan
C
Qi
Tong
T
Wang
D000818:Animals; D001835:Body Weight / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects*; D019422:Dietary Sucrose / Q000009:adverse effects*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis*; D044105:Receptor, Melanocortin, Type 4 / Q000096:biosynthesis; D014886:Weaning
D019422:Dietary Sucrose; C574273:MC4R protein, mouse; D044105:Receptor, Melanocortin, Type 4; D011333:Pro-Opiomelanocortin; D005947:Glucose