Jiayu Lu1,2,3, Ying Gong4,2,3, Xinhong Wei5, Zhenyu Yao4,2,3, Rui Yang6, Jinxing Xin1,2,3, Ling Gao2,3,7, Shanshan Shao8,9,10. 1. Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 544, Jing 4 Rd., Jinan, 250021, Shandong, China. 2. Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, 250021, Shandong, China. 3. Shandong Institute of Endocrine and Metabolic Disease, Jinan, 250021, Shandong, China. 4. Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China. 5. Shandong Medical Imaging Research Institute, Shandong University, Jinan, 250021, Shandong, China. 6. Experimental Animal Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. 7. Scientific Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. 8. Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 544, Jing 4 Rd., Jinan, 250021, Shandong, China. shaoshanshan11@126.com. 9. Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, 250021, Shandong, China. shaoshanshan11@126.com. 10. Shandong Institute of Endocrine and Metabolic Disease, Jinan, 250021, Shandong, China. shaoshanshan11@126.com.
Abstract
BACKGROUND: To meet the needs of foetal growth and development, marked changes in lipid profiles occur during pregnancy. Abnormal lipid metabolism is often accompanied by adverse pregnancy outcomes, which seriously affect maternal and infant health. Further understanding of the mechanism of lipid metabolism during pregnancy would be helpful to reduce the incidence of adverse pregnancy outcomes. METHODS: Pregnant mice were euthanized in the virgin (V) state, on day 5 of pregnancy (P5), on day 12 of pregnancy (P12), on day 19 of pregnancy (P19) and on lactation day 2 (L2). Body weight and energy expenditure were assessed to evaluate the general condition of the mice. Triglyceride (TG) levels, the cholesterol content in the liver, liver histopathology, serum lipid profiles, serum β-hydroxybutyrate levels, fibroblast growth factor-21 (FGF21) levels and the levels of relevant target genes were analysed. RESULTS: During early pregnancy, anabolism was found to play a major role in liver lipid deposition. In contrast, advanced pregnancy is an overall catabolic condition associated with both increased energy expenditure and reduced lipogenesis. Moreover, the accumulation of hepatic TG did not appear until P12, after the onset of endoplasmic reticulum (ER) stress on P5. Then, catabolism was enhanced, and FGF21 secretion was increased in the livers of female mice in late pregnancy. We further found that the expression of sec23a, which as the coat protein complex II (COPII) vesicle coat proteins regulates the secretion of FGF21, in the liver was decreased on P19. CONCLUSION: With the activation of ER stress and increased FGF21 secretion during pregnancy, the hepatic TG content changes, suggesting that ER stress and FGF21 may play an important role in balancing lipid homeostasis and meeting maternal and infant energy requirements in late pregnancy.
BACKGROUND: To meet the needs of foetal growth and development, marked changes in lipid profiles occur during pregnancy. Abnormal lipid metabolism is often accompanied by adverse pregnancy outcomes, which seriously affect maternal and infant health. Further understanding of the mechanism of lipid metabolism during pregnancy would be helpful to reduce the incidence of adverse pregnancy outcomes. METHODS: Pregnant mice were euthanized in the virgin (V) state, on day 5 of pregnancy (P5), on day 12 of pregnancy (P12), on day 19 of pregnancy (P19) and on lactation day 2 (L2). Body weight and energy expenditure were assessed to evaluate the general condition of the mice. Triglyceride (TG) levels, the cholesterol content in the liver, liver histopathology, serum lipid profiles, serum β-hydroxybutyrate levels, fibroblast growth factor-21 (FGF21) levels and the levels of relevant target genes were analysed. RESULTS: During early pregnancy, anabolism was found to play a major role in liverlipid deposition. In contrast, advanced pregnancy is an overall catabolic condition associated with both increased energy expenditure and reduced lipogenesis. Moreover, the accumulation of hepatic TG did not appear until P12, after the onset of endoplasmic reticulum (ER) stress on P5. Then, catabolism was enhanced, and FGF21 secretion was increased in the livers of female mice in late pregnancy. We further found that the expression of sec23a, which as the coat protein complex II (COPII) vesicle coat proteins regulates the secretion of FGF21, in the liver was decreased on P19. CONCLUSION: With the activation of ERstress and increased FGF21 secretion during pregnancy, the hepatic TG content changes, suggesting that ERstress and FGF21 may play an important role in balancing lipid homeostasis and meeting maternal and infant energy requirements in late pregnancy.
Authors: Rachel Kadakia; Michael Nodzenski; Octavious Talbot; Alan Kuang; James R Bain; Michael J Muehlbauer; Robert D Stevens; Olga R Ilkayeva; Sara K O'Neal; Lynn P Lowe; Boyd E Metzger; Christopher B Newgard; Denise M Scholtens; William L Lowe Journal: Diabetologia Date: 2018-11-27 Impact factor: 10.122
Authors: Yufeng Zhang; Christine Kallenberg; Hayden W Hyatt; Andreas N Kavazis; Wendy R Hood Journal: Front Physiol Date: 2017-07-26 Impact factor: 4.566