title: High levels of chorionic gonadotrophin attenuate insulin sensitivity and promote inflammation in adipocytes.
abstract: Gestational diabetes mellitus (GDM) presents with moderate inflammation, insulin resistance and impaired glucose uptake, which may result from increased maternal fat mass and increased circulation of placental hormones and adipokines. In this study, we set out to test whether the surge in chorionic gonadotrophin (CG) secretion is a cause of inflammation and impaired insulin sensitivity in GDM. We first found that LH/chorionic gonadotrophin receptors (CG/LHR) were expressed at low levels in insulin-sensitive murine 3T3-L1 adipocytes and murine C2C12 myocytes. CG treatment not only directly reduced insulin-responsive gene expression, including that of glucose transporter 4 (GLUT4), but also impaired insulin-stimulated glucose uptake in 3T3-L1 cells. Moreover, CG treatment increased the expression of the proinflammatory cytokine monocyte chemotactic protein 1 (MCP1) and upregulated nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activity in 3T3-L1 cells. Clinically, pregnant women who had higher CG levels and elevated MCP1 developed GDM. Above all, apart from prepregnancy BMI and MCP1 level, CG level was associated with abnormal glucose tolerance. In summary, our findings confirmed that higher CG levels in pregnancy possibly played a role in GDM development partly by impairing the functions of insulin, such those involved in as glucose uptake, while promoting inflammation in adipocyte.
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors and E-Institute of Shanghai UniversitiesDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, China National Clinical Research for Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, ChinaDepartment of Obstetrics and GynecologyInternational Peace Maternity and Child Health Hospital affiliated Shanghai Jiaotong University School of Medicine, 910 Hengshan Road, Shanghai 200030, ChinaDepartment of Obstetrics and GynecologyObstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: Qinyun
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors and E-Institute of Shanghai UniversitiesDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, China National Clinical Research for Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, ChinaDepartment of Obstetrics and GynecologyInternational Peace Maternity and Child Health Hospital affiliated Shanghai Jiaotong University School of Medicine, 910 Hengshan Road, Shanghai 200030, ChinaDepartment of Obstetrics and GynecologyObstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: Jianxia
authors.initials: J
authors.lastname: Fan
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors and E-Institute of Shanghai UniversitiesDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, China National Clinical Research for Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, ChinaDepartment of Obstetrics and GynecologyInternational Peace Maternity and Child Health Hospital affiliated Shanghai Jiaotong University School of Medicine, 910 Hengshan Road, Shanghai 200030, ChinaDepartment of Obstetrics and GynecologyObstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: Jiqiu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors and E-Institute of Shanghai UniversitiesDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, China National Clinical Research for Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, ChinaDepartment of Obstetrics and GynecologyInternational Peace Maternity and Child Health Hospital affiliated Shanghai Jiaotong University School of Medicine, 910 Hengshan Road, Shanghai 200030, ChinaDepartment of Obstetrics and GynecologyObstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors and E-Institute of Shanghai UniversitiesDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, China National Clinical Research for Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, ChinaDepartment of Obstetrics and GynecologyInternational Peace Maternity and Child Health Hospital affiliated Shanghai Jiaotong University School of Medicine, 910 Hengshan Road, Shanghai 200030, ChinaDepartment of Obstetrics and GynecologyObstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cong
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors and E-Institute of Shanghai UniversitiesDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, China National Clinical Research for Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, ChinaDepartment of Obstetrics and GynecologyInternational Peace Maternity and Child Health Hospital affiliated Shanghai Jiaotong University School of Medicine, 910 Hengshan Road, Shanghai 200030, ChinaDepartment of Obstetrics and GynecologyObstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors and E-Institute of Shanghai UniversitiesDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, China National Clinical Research for Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, ChinaDepartment of Obstetrics and GynecologyInternational Peace Maternity and Child Health Hospital affiliated Shanghai Jiaotong University School of Medicine, 910 Hengshan Road, Shanghai 200030, ChinaDepartment of Obstetrics and GynecologyObstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors and E-Institute of Shanghai UniversitiesDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, China National Clinical Research for Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, ChinaDepartment of Obstetrics and GynecologyInternational Peace Maternity and Child Health Hospital affiliated Shanghai Jiaotong University School of Medicine, 910 Hengshan Road, Shanghai 200030, ChinaDepartment of Obstetrics and GynecologyObstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: Ruixin
authors.initials: R
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors and E-Institute of Shanghai UniversitiesDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, China National Clinical Research for Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, ChinaDepartment of Obstetrics and GynecologyInternational Peace Maternity and Child Health Hospital affiliated Shanghai Jiaotong University School of Medicine, 910 Hengshan Road, Shanghai 200030, ChinaDepartment of Obstetrics and GynecologyObstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, China gning@sibs.ac.cn.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000097:blood* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D016640:Diabetes, Gestational / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011247:Pregnancy; D011974:Receptors, LH / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D006063:Chorionic Gonadotropin; D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; D016328:NF-kappa B; D011974:Receptors, LH; D051550:I-kappa B Kinase
keywords: 3T3-L1 cells; chorionic gonadotrophin (CG); gestational diabetes mellitus (GDM); insulin resistance; proinflammation