低剂量双酚A通过调控PPARγ致小鼠糖脂代谢紊乱的研究

doi:10.3969/j.issn.1004-616x.2020.04.001

Abstract

Abstract: OBJECTIVE: To investigate the effect and mechanism of low doses of bisphenol A (BPA) alone or in combination with high fat diet (HFD) on glucose and lipid metabolism in mice. METHODS: Sixty C57BL/6J mice were randomly divided into five groups for exposure to BPA at different concentrations[1,10, 100,1 000 μg/(kg·d)]. After determining the optimal dose,another 60 C57BL/6J mice were randomly divided into 5 groups:control,BPA,BPA+HFD,HFD,BPA+Ginsenoside Rh1 (Rh1). The function of glucose and lipid metabolism in mice was evaluated by measuring liver triglyceride (TG) content and glucose tolerance. RESULTS: After exposure of 10 μg/(kg·d) BPA,morphological and biochemical determinations showed that these mice had the highest lipid accumulation. Compared with the control group, BPA exposure resulted in increased liver TG levels and decreased glucose tolerance (P < 0.05). Compared with HFD group,mice from the BPA + HFD group had increased liver TG content and decreased glucose tolerance (P < 0.05). Expression levels of peroxidosomal proliferator activated receptor γ (PPARγ), sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FASN) and stearyl coenzyme A desaturase 1 (SCD-1), which are related to adipogenesis, were significantly increased (P < 0.05). In BPA exposed mice treated with Rh1, liver TG levels were significantly reduced compared with the BPA exposed mice (P < 0.05). CONSLUSION: BPA exposure induced glucose and lipid metabolism disorders in mice, and aggravate HFD-induced glucose and lipid metabolism disorders. BPA regulated a series of lipid metabolism-related genes to induce lipid accumulation, leading to the disorder of glucose and lipid metabolism. Inhibition of PPARγ expression with Rh1 significantly alleviated BPA-induced disorders of glucose and lipid metabolism. Therefore, increased PPARγ transcription could be a key reason of glucose and lipid metabolism disorder induced by BPA.

Key words: bisphenol A, low dose exposure, high fat diet, PPARγ, glucose and lipid metabolic disorder

CLC Number:

R994.6

LONG Zi, FAN Junshu, WU Guangyuan, WANG Xin, HAI Chunxu. Low-dose of bisphenol A induced glucose and lipid metabolism disorders in mice by regulating PPARγ[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(4): 245-255.

References

[1] LOOMBA R, SANYAL A J. The global NAFLD epidemic[J]. Nat Rev Gastroenterol Hepatol, 2013, 10(11):686-690.
[2] MACHADO M V, CORTEZ-PINTO H. Non-alcoholic fatty liver disease:what the clinician needs to know[J]. World J Gastroenterol, 2014, 20(36):12956-12980.
[3] WANG J, SUN B, HOU M, et al. The environmental obesogen bisphenol A promotes adipogenesis by increasing the amount of 11β-hydroxysteroid dehydrogenase type 1 in the adipose tissue of children[J]. Int J Obes (Lond), 2013, 37(7):999-1005.
[4] MARMUGI A, DUCHEIX S, LASSERRE F, et al. Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumulation in adult mouse liver[J]. Hepatology, 2012, 55(2):395-407.
[5] BAILLIE-HAMILTON P F. Chemical toxins:a hypothesis to explain the global obesity epidemic[J]. J Altern Complement Med, 2002, 8(2):185-192.
[6] VANDENBERG L N, HAUSER R, MARCUS M, et al. Human exposure to bisphenol A (BPA)[J]. Reproductive Toxicol, 2007, 24(2):139-177.
[7] DING S B, FAN Y, ZHAO N N, et al. High-fat diet aggravates glucose homeostasis disorder caused by chronic exposure to bisphenol A[J]. J Endocrinol, 2014, 221(1):167-179.
[8] HALDEN R U. Plastics and health risks[J]. Annu Rev Public Health, 2010, 31:179-194.
[9] ARNOLD S M, CLARK K E, STAPLES C A, et al. Relevance of drinking water as a source of human exposure to bisphenol A[J]. J Expo Sci Environ Epidemiol, 2013, 23(2):137-144.
[10] COLIN A, BACH C, ROSIN C, et al. Is drinking water a major route of human exposure to alkylphenol and bisphenol contaminants in France?[J]. Arch Environ Contam Toxicol, 2014, 66(1):86-99.
[11] VANDENBERG L N, CHAHOUD I, HEINDEL J J, et al. Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A[J]. Environ Health Perspect, 2010, 118(8):1055-1070.
[12] WELSHONS W V, NAGEL S C, VOM SAAL F S. Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure[J]. Endocrinology, 2006, 147(Sup 6):S56-S69.
[13] CALAFAT A M, YE X Y, WONG L Y, et al. Exposure of the US population to bisphenol A and 4-tertiary-octylphenol:2003-2004[J]. Environ Health Perspect, 2008, 116(1):39-44.
[14] SAJIKI J, TAKAHASHI K, YONEKUBO J. Sensitive method for the determination of bisphenol-A in serum using two systems of high-performance liquid chromatography[J]. J Chromatogr B Biomed Sci Appl, 1999, 736(1/2):255-261.
[15] VOM SAAL F S, WELSHONS W V. Evidence that bisphenol A (BPA) can be accurately measured without contamination in human serum and urine, and that BPA causes numerous hazards from multiple routes of exposure[J]. Mol Cell Endocrinol, 2014, 398(1/2):101-113.
[16] SAVASTANO S, TARANTINO G, D'ESPOSITO V, et al. Bisphenol-A plasma levels are related to inflammatory markers, visceral obesity and insulin-resistance:a cross-sectional study on adult male population[J]. J Transl Med, 2015, 13:169.
[17] CAMARCA A, GIANFRANI C, ARIEMMA F, et al. Human peripheral blood mononuclear cell function and dendritic cell differentiation are affected by bisphenol-A exposure[J]. PLoS One, 2016, 11(8):e0161122.
[18] HOWDESHELL K L, HOTCHKISS A K, THAYER K A, et al. Exposure to bisphenol A advances puberty[J]. Nature, 1999, 401(6755):763-764.
[19] CABATON N J, WADIA P R, RUBIN B S, et al. Perinatal exposure to environmentally relevant levels of bisphenol A decreases fertility and fecundity in CD-1 mice[J]. Environ Health Perspect, 2011, 119(4):547-552.
[20] SALIAN S, DOSHI T, VANAGE G. Neonatal exposure of male rats to Bisphenol A impairs fertility and expression of Sertoli cell junctional proteins in the testis[J]. Toxicology, 2009, 265(1/2):56-67.
[21] MANIKKAM M, TRACEY R, GUERRERO-BOSAGNA C, et al. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations[J]. PLoS One, 2013, 8(1):e55387.
[22] MARTELLA A, SILVESTRI C, MARADONNA F, et al. Bisphenol A induces fatty liver by an endocannabinoid-mediated positive feedback loop[J]. Endocrinology, 2016, 157(5):1751-1763.
[23] VOM SAAL F S. Bisphenol A and risk of metabolic disorders[J]. JAMA, 2008, 300(11):1353.
[24] PRINS G S, BIRCH L, TANG W Y, et al. Developmental estrogen exposures predispose to prostate carcinogenesis with aging[J]. Reprod Toxicol, 2007, 23(3):374-382.
[25] BHANDARI R, XIAO J, SHANKAR A. Urinary bisphenol A and obesity in US children[J]. Am J Epidemiol, 2013, 177(11):1263-1270.
[26] DOLINOY D C, JIRTLE R L. Environmental epigenomics in human health and disease[J]. Environ Mol Mutagen, 2008, 49(1):4-8.
[27] HUGO E R, BRANDEBOURG T D, WOO J G, et al. Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose tissue explants and adipocytes[J]. Environ Health Perspect, 2008, 116(12):1642-1647.
[28] LANG I A, GALLOWAY T S, SCARLETT A, et al. Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults[J]. JAMA, 2008, 300(11):1303-1310.
[29] LI D, ZHOU Z, QING D, et al. Occupational exposure to bisphenol-A (BPA) and the risk of self-reported male sexual dysfunction[J]. Hum Reprod, 2010, 25(2):519-527.
[30] VALENTINO R, D'ESPOSITO V, ARIEMMA F, et al. Bisphenol A environmental exposure and the detrimental effects on human metabolic health:is it necessary to revise the risk assessment in vulnerable population?[J]. J Endocrinol Invest, 2016, 39(3):259-263.
[31] MELZER D, RICE, LEWIS C, et al. Association of urinary bisphenol a concentration with heart disease:evidence from NHANES 2003/06[J]. PLoS One, 2010, 5(1):e8673.
[32] BIEDERMANN S, TSCHUDIN P, GROB K. Transfer of bisphenol A from thermal printer paper to the skin[J]. Anal Bioanal Chem, 2010, 398(1):571-576.
[33] BERNIER M R, VANDENBERG L N. Handling of thermal paper:Implications for dermal exposure to bisphenol A and its alternatives[J]. PLoS One, 2017, 12(6):e0178449.
[34] MARMUGI A, LASSERRE F, BEUZELIN D, et al. Adverse effects of long-term exposure to bisphenol A during adulthood leading to hyperglycaemia and hypercholesterolemia in mice[J]. Toxicology, 2014, 325:133-143.
[35] NEUSCHWANDER-TETRI B A. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis:the central role of nontriglyceride fatty acid metabolites[J]. Hepatology, 2010, 52(2):774-788.
[36] MATSUSUE K, AIBARA D, HAYAFUCHI R, et al. Hepatic PPARγ and LXRα independently regulate lipid accumulation in the livers of genetically obese mice[J]. FEBS Lett, 2014, 588(14):2277-2281.
[37] TAM D N H, TRUONG D H, NGUYEN T T H, et al. Ginsenoside Rh1:a systematic review of its pharmacological properties[J]. Planta Med, 2018, 84(3):139-152.
[38] GU W, KIM K A, KIM D H. Ginsenoside Rh1 ameliorates high fat diet-induced obesity in mice by inhibiting adipocyte differentiation[J]. Biol Pharm Bull, 2013, 36(1):102-107.

Low-dose of bisphenol A induced glucose and lipid metabolism disorders in mice by regulating PPARγ

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 5

Recommended Articles

Metrics

Comments

[1]	LIAO Nai, LONG Zi, HAI Chunxu, WANG Xin. 2,3,7,8-tetrachlorodibenzo-p-dioxin alone or in combination with high fat diet on glucose and lipid metabolism in mice [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(2): 111-118.
[2]	CHEN Yin-chang;HAO Wei-dong;SHANG Lan-qin;WEI Xue-tao;JIANG Jian-jun;LIU Ran;XING Li-na;WU Shuang. The effect of perinatal exposure to Bisophenol A on reproductive system of female offspring rats and changes in expression of estrogen receptor [J]. , 2010, 22(3): 196-201.
[3]	WU Shuang;WEI Xue-tao; HAO Wei-dong. Effects of Bisphenol A and Diazinon on Proliferation of MCF-7 Cells [J]. , 2009, 21(4): 249-253.
[4]	SONG Qing_kun, HAO Wei_dong, SHANG Lan_qin, WEI Xue_tao, JIANG Jian_jun, XING Li_na, WANG Hui, WU Shuang, ZHAO Yan, QIAO Yang_zheng, HAO Chang_fu. The Effects of Bisphenol A on Reproduction and Development of Pubertal Male Rats [J]. , 2008, 20(4): 267-271.
[5]	HUANG Yi-na, CHENG Wei-bo, XU Pei-yu, YU Wen-san, etal.. IMMATURE SD RAT UTEROTROPHIC ASSAY OF BISPHENOL A [J]. , 2002, 14(4): 234-237.