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• How does protein misfolding in the endoplasmic reticulum affect lipid metabolism in the liver?

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         headline:Changes in hepatic triglyceride content with the activation of ER stress and increased FGF21 secretion during pregnancy
         description: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. 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. 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. 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.
         datePublished:2021-04-13T00:00:00Z
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            Endoplasmic reticulum stress
            FGF21
            Pregnancy
            Lipid metabolism
            Clinical Nutrition
            Metabolic Diseases
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      headline:Changes in hepatic triglyceride content with the activation of ER stress and increased FGF21 secretion during pregnancy
      description: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. 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. 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. 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.
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         FGF21
         Pregnancy
         Lipid metabolism
         Clinical Nutrition
         Metabolic Diseases
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            name:Shandong University
            address:
               name:Shandong Medical Imaging Research Institute, Shandong University, Jinan, China
               type:PostalAddress
            type:Organization
      name:Zhenyu Yao
      affiliation:
            name:Shandong University
            address:
               name:Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
               type:PostalAddress
            type:Organization
            name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism
            address:
               name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
               type:PostalAddress
            type:Organization
            name:Shandong Institute of Endocrine and Metabolic Disease
            address:
               name:Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
               type:PostalAddress
            type:Organization
      name:Rui Yang
      affiliation:
            name:Shandong Provincial Hospital Affiliated to Shandong First Medical University
            address:
               name:Experimental Animal Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
               type:PostalAddress
            type:Organization
      name:Jinxing Xin
      affiliation:
            name:Shandong Provincial Hospital Affiliated to Shandong First Medical University
            address:
               name:Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
               type:PostalAddress
            type:Organization
            name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism
            address:
               name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
               type:PostalAddress
            type:Organization
            name:Shandong Institute of Endocrine and Metabolic Disease
            address:
               name:Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
               type:PostalAddress
            type:Organization
      name:Ling Gao
      affiliation:
            name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism
            address:
               name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
               type:PostalAddress
            type:Organization
            name:Shandong Institute of Endocrine and Metabolic Disease
            address:
               name:Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
               type:PostalAddress
            type:Organization
            name:Shandong Provincial Hospital Affiliated to Shandong First Medical University
            address:
               name:Scientific Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
               type:PostalAddress
            type:Organization
      name:Shanshan Shao
      url:http://orcid.org/0000-0002-7759-3938
      affiliation:
            name:Shandong Provincial Hospital Affiliated to Shandong First Medical University
            address:
               name:Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
               type:PostalAddress
            type:Organization
            name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism
            address:
               name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
               type:PostalAddress
            type:Organization
            name:Shandong Institute of Endocrine and Metabolic Disease
            address:
               name:Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
      name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
      name:Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
      name:Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
      name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
      name:Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
      name:Shandong Medical Imaging Research Institute, Shandong University, Jinan, China
      name:Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
      name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
      name:Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
      name:Experimental Animal Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
      name:Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
      name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
      name:Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
      name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
      name:Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
      name:Scientific Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
      name:Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
      name:Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
      name:Shandong Institute of Endocrine and Metabolic Disease, Jinan, China

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