PMID- 25691497 OWN - NLM STAT- MEDLINE DCOM- 20151222 LR - 20150320 IS - 1479-6813 (Electronic) IS - 0952-5041 (Linking) VI - 54 IP - 2 DP - 2015 Apr TI - High levels of chorionic gonadotrophin attenuate insulin sensitivity and promote inflammation in adipocytes. PG - 161-70 LID - 10.1530/JME-14-0284 [doi] AB - 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 kappa-light-chain-enhancer of activated B cells (NF-kappaB) 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. CI - (c) 2015 Society for Endocrinology. FAU - Ma, Qinyun AU - Ma Q AD - 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. FAU - Fan, Jianxia AU - Fan J AD - 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. FAU - Wang, Jiqiu AU - Wang J AD - 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. FAU - Yang, Shuai AU - Yang S AD - 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. FAU - Cong, Qing AU - Cong Q AD - 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. FAU - Wang, Rui AU - Wang R AD - 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. FAU - Lv, Qianqian AU - Lv Q AD - 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. FAU - Liu, Ruixin AU - Liu R AD - 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. FAU - Ning, Guang AU - Ning G AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150217 PL - England TA - J Mol Endocrinol JT - Journal of molecular endocrinology JID - 8902617 RN - 0 (Blood Glucose) RN - 0 (Chorionic Gonadotropin) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Insulin) RN - 0 (NF-kappa B) RN - 0 (Receptors, LH) RN - EC 2.7.11.10 (I-kappa B Kinase) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/drug effects/metabolism/*pathology MH - Adult MH - Animals MH - Blood Glucose/metabolism MH - Chorionic Gonadotropin/*blood/pharmacology MH - Cytokines/metabolism MH - Diabetes, Gestational/blood MH - Female MH - Glucose Tolerance Test MH - Humans MH - I-kappa B Kinase/metabolism MH - Inflammation/metabolism/*pathology MH - Inflammation Mediators/metabolism MH - Insulin/*pharmacology MH - Mice MH - NF-kappa B/metabolism MH - Pregnancy MH - Receptors, LH/metabolism MH - Signal Transduction/drug effects OTO - NOTNLM OT - 3T3-L1 cells OT - chorionic gonadotrophin (CG) OT - gestational diabetes mellitus (GDM) OT - insulin resistance OT - proinflammation EDAT- 2015/02/19 06:00 MHDA- 2015/12/23 06:00 CRDT- 2015/02/19 06:00 PHST- 2015/02/19 06:00 [entrez] PHST- 2015/02/19 06:00 [pubmed] PHST- 2015/12/23 06:00 [medline] AID - JME-14-0284 [pii] AID - 10.1530/JME-14-0284 [doi] PST - ppublish SO - J Mol Endocrinol. 2015 Apr;54(2):161-70. doi: 10.1530/JME-14-0284. Epub 2015 Feb 17.