title: Bisphenol A Promotes Adiposity and Inflammation in a Nonmonotonic Dose-response Way in 5-week-old Male and Female C57BL/6J Mice Fed a Low-calorie Diet.
abstract: A growing body of epidemiological research show that Bisphenol A (BPA) is positively correlated with obesity and metabolic disorders. However, the mechanisms of BPA on adiposity remain largely unknown. In this study, we found that 5-week-old male and female C57BL/6J mice exposed to four dosages of BPA (5, 50, 500, and 5000 μg/kg/d) by oral intake for 30 days showed significantly increased body weight and fat mass in a nonmonotonic dose-dependent manner when fed a chow diet. The effect occurred even at the lowest concentration (5μg/kg/d), lower than the tolerable daily intake of 50 μg/kg/day for BPA. However, no significant difference in body weight and fat mass was observed in either male or female mice fed a high-fat diet, suggesting that BPA may interact with diet in promoting obesity risk. In vitro study showed that BPA treatment drives the differentiation of white adipocyte progenitors from the stromal vascular fraction, partially through glucocorticoid receptor. BPA exposure increased circulating inflammatory factors and the local inflammation in white adipose tissues in both genders fed a chow diet, but not under high-fat diet. We further found that BPA concentration was associated with increased circulating inflammatory factors, including leptin and TNFα, in lean female subjects (body mass index < 23.0 kg/m(2)) but not in lean male subjects or in both sexes of overweight/obese subjects (body mass index > 25.0 kg/m(2)). In conclusion, we demonstrated the nonmonotonic dose effects of BPA on adiposity and chronic inflammation in 5-week-old mice, which is related to caloric uptake.
authors.affiliation: Shanghai Rui-Jin Hospital (M.Y., M.C., J.W., M.X., L.D., X.L., Q.M., Y.B., R.L., J.H., G.N.), Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai 200025, China; and Laboratory for Endocrine & Metabolic Diseases (J.S.), Institute of Health Science, Shanghai Jiao-Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Minglan
authors.initials: M
authors.lastname: Yang
authors.affiliation: Shanghai Rui-Jin Hospital (M.Y., M.C., J.W., M.X., L.D., X.L., Q.M., Y.B., R.L., J.H., G.N.), Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai 200025, China; and Laboratory for Endocrine & Metabolic Diseases (J.S.), Institute of Health Science, Shanghai Jiao-Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Maopei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Shanghai Rui-Jin Hospital (M.Y., M.C., J.W., M.X., L.D., X.L., Q.M., Y.B., R.L., J.H., G.N.), Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai 200025, China; and Laboratory for Endocrine & Metabolic Diseases (J.S.), Institute of Health Science, Shanghai Jiao-Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Jiqiu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Rui-Jin Hospital (M.Y., M.C., J.W., M.X., L.D., X.L., Q.M., Y.B., R.L., J.H., G.N.), Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai 200025, China; and Laboratory for Endocrine & Metabolic Diseases (J.S.), Institute of Health Science, Shanghai Jiao-Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Shanghai Rui-Jin Hospital (M.Y., M.C., J.W., M.X., L.D., X.L., Q.M., Y.B., R.L., J.H., G.N.), Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai 200025, China; and Laboratory for Endocrine & Metabolic Diseases (J.S.), Institute of Health Science, Shanghai Jiao-Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Jichao
authors.initials: J
authors.lastname: Sun
authors.affiliation: Shanghai Rui-Jin Hospital (M.Y., M.C., J.W., M.X., L.D., X.L., Q.M., Y.B., R.L., J.H., G.N.), Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai 200025, China; and Laboratory for Endocrine & Metabolic Diseases (J.S.), Institute of Health Science, Shanghai Jiao-Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ding
authors.affiliation: Shanghai Rui-Jin Hospital (M.Y., M.C., J.W., M.X., L.D., X.L., Q.M., Y.B., R.L., J.H., G.N.), Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai 200025, China; and Laboratory for Endocrine & Metabolic Diseases (J.S.), Institute of Health Science, Shanghai Jiao-Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Lv
authors.affiliation: Shanghai Rui-Jin Hospital (M.Y., M.C., J.W., M.X., L.D., X.L., Q.M., Y.B., R.L., J.H., G.N.), Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai 200025, China; and Laboratory for Endocrine & Metabolic Diseases (J.S.), Institute of Health Science, Shanghai Jiao-Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Qinyun
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Shanghai Rui-Jin Hospital (M.Y., M.C., J.W., M.X., L.D., X.L., Q.M., Y.B., R.L., J.H., G.N.), Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai 200025, China; and Laboratory for Endocrine & Metabolic Diseases (J.S.), Institute of Health Science, Shanghai Jiao-Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Shanghai Rui-Jin Hospital (M.Y., M.C., J.W., M.X., L.D., X.L., Q.M., Y.B., R.L., J.H., G.N.), Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai 200025, China; and Laboratory for Endocrine & Metabolic Diseases (J.S.), Institute of Health Science, Shanghai Jiao-Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Ruixin
authors.initials: R
authors.lastname: Liu
authors.affiliation: Shanghai Rui-Jin Hospital (M.Y., M.C., J.W., M.X., L.D., X.L., Q.M., Y.B., R.L., J.H., G.N.), Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai 200025, China; and Laboratory for Endocrine & Metabolic Diseases (J.S.), Institute of Health Science, Shanghai Jiao-Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.affiliation: Shanghai Rui-Jin Hospital (M.Y., M.C., J.W., M.X., L.D., X.L., Q.M., Y.B., R.L., J.H., G.N.), Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai 200025, China; and Laboratory for Endocrine & Metabolic Diseases (J.S.), Institute of Health Science, Shanghai Jiao-Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D050154:Adiposity / Q000187:drug effects / Q000235:genetics; D000368:Aged; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D031204:Caloric Restriction; D002454:Cell Differentiation / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D020738:Leptin; D010636:Phenols; D011965:Receptors, Glucocorticoid; C006780:bisphenol A; D000098826:Bisphenol A Compounds