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中华肥胖与代谢病电子杂志 ›› 2024, Vol. 10 ›› Issue (03) : 177 -183. doi: 10.3877/cma.j.issn.2095-9605.2024.03.004

青年专家论坛

肥胖与胆囊疾病研究进展
王思奇, 张念荣, 周彪, 刘宝胤, 孟化()   
  1. 100029 北京,中日友好医院普外科·代谢减重中心
  • 收稿日期:2024-03-10 出版日期:2024-08-30
  • 通信作者: 孟化
  • 基金资助:
    中日友好医院"菁英计划"人才培育工程(ZRJY2024-GG09); 中日友好医院中央高水平医院临床科研业务费(2024-NHLHCRF-PY II-06; ZRJY2024-GG09; 2023-NHLHCRF-YYPP-TS-02;2023-NHLHCRF-YS-0103)

Progress in research on obesity and gallbladder diseases

Siqi Wang, Nianrong Zhang, Biao Zhou, Baoyin Liu, Hua Meng()   

  1. Department of General Surgery and Obesity and Metabolic Disease Center, China-Japan Friendship Hospital, Beijing 100029, China
  • Received:2024-03-10 Published:2024-08-30
  • Corresponding author: Hua Meng
引用本文:

王思奇, 张念荣, 周彪, 刘宝胤, 孟化. 肥胖与胆囊疾病研究进展[J]. 中华肥胖与代谢病电子杂志, 2024, 10(03): 177-183.

Siqi Wang, Nianrong Zhang, Biao Zhou, Baoyin Liu, Hua Meng. Progress in research on obesity and gallbladder diseases[J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2024, 10(03): 177-183.

近年来,肥胖已成为全球性的公共卫生问题,严重损害人类生命健康。肥胖作为全身性的代谢性疾病,与多种胆囊疾病的发生发展相关。大量研究表明肥胖与胆囊结石、胆囊炎症和胆囊恶性肿瘤之间存在着密切联系。本文总结了肥胖与胆囊疾病之间的生理和代谢机制,同时探讨了减重过程中伴随的胆囊疾病风险,旨在阐明肥胖对胆囊的重要影响,并强调科学减重对维护胆囊健康的必要性,为开展共患人群的科学防治提供参考依据。

In recent years, obesity has become a global public health problem, seriously damaging human health. At the same time, obesity, as a systemic metabolic disease, is closely related to a variety of gallbladder diseases. A large number of studies have shown a close correlation between obesity and gallbladder stones, gallbladder inflammation and gallbladder malignancy. This article summarizes the physiological and metabolic mechanisms linking obesity and gallbladder diseases, and explores the risks of gallbladder diseases associated with weight loss. It aims to clarify the significant impact of obesity on gallbladder health and emphasizes the necessity of scientific weight loss for maintaining gallbladder health, providing a reference for the scientific prevention and treatment of comorbid populations.

图1 肥胖影响胆囊结石生成的多个途径
图2 肥胖引起胆囊恶性肿瘤的机制注:IGFBP为胰岛素样生长因子结合蛋白;IGF-1为胰岛素样生长因子-1;IR为胰岛素受体;IGF-IR为胰岛素样生长因子受体;Ras/Raf/MAPK为Ras/Raf/丝裂原活化蛋白激酶;TNF-α为肿瘤坏死因子-α;IL-6为白细胞介素-6;AMPK为腺苷酸活化蛋白激酶;PI3K为磷脂酰肌醇3-激酶;Akt为蛋白激酶B
[1]
Wang Y, Zhao L, Gao L, et al. Health policy and public health implications of obesity in China [J]. Lancet Diabetes Endocrinol, 2021, 9(7): 446-461.
[2]
Bray GA, Kim KK, Wilding JPH, et al. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation [J]. Obes Rev, 2017, 18(7): 715-723.
[3]
Hurt RT, Edakkanambeth Varayil J, Mundi MS, et al. Designation of obesity as a disease: lessons learned from alcohol and tobacco [J]. Curr Gastroenterol Rep, 2014, 16(11): 415.
[4]
Avgerinos KI, Spyrou N, Mantzoros CS, et al. Obesity and cancer risk: Emerging biological mechanisms and perspectives [J]. Metabolism, 2019, 92: 121-135.
[5]
Mendez-Sanchez N, Chavez-Tapia NC, Uribe M. Gallbladder disease and obesity.[J]. Gac Med Mex, 2004, 140(Suppl 2): S59-66.
[6]
Cariou B, Chetiveaux M, Zaïr Y, et al. Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults [J]. Nutr Metab (Lond), 2011, 8(1): 48.
[7]
Glicksman C, Pournaras DJ, Wright M, et al. Postprandial plasma bile acid responses in normal weight and obese subjects [J]. Ann Clin Biochem, 2010, 47(Pt 5): 482-484.
[8]
Haeusler RA, Astiarraga B, Camastra S, et al. Human insulin resistance is associated with increased plasma levels of 12alpha-hydroxylated bile acids [J]. Diabetes, 2013, 62(12): 4184-4191.
[9]
Watanabe M, Houten SM, Wang L, et al. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c [J]. J Clin Invest, 2004, 113(10): 1408-1418.
[10]
Sayin SI, Wahlström A, Felin J, et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist [J]. Cell Metab, 2013, 17(2): 225-235.
[11]
European Association for the Study of the Liver (EASL). Electronic address: easloffice@easloffice.eu. EASL Clinical Practice Guidelines on the prevention, diagnosis and treatment of gallstones [J]. J Hepatol, 2016, 65(1): 146-181.
[12]
Wang DQ, Cohen DE, Carey MC. Biliary lipids and cholesterol gallstone disease [J]. J Lipid Res, 2009, 50 Suppl(Suppl): S406-411.
[13]
Aune D, Norat T, Vatten LJ. Body mass index, abdominal fatness and the risk of gallbladder disease [J]. Eur J Epidemiol, 2015, 30(9): 1009-1019.
[14]
Méndez-Sánchez N, Chávez-Tapia NC, Zamora-Valdés D, et al. Hepatobiliary diseases and insulin resistance [J]. Curr Med Chem, 2007, 14(18): 1988-1999.
[15]
Leitzmann MF, Giovannucci EL, Rimm EB, et al. The relation of physical activity to risk for symptomatic gallstone disease in men [J]. Ann Intern Med, 1998, 128(6): 417-425.
[16]
Portincasa P, Di Ciaula A, Palmieri V, et al. Effects of cholestyramine on gallbladder and gastric emptying in obese and lean subjects [J]. Eur J Clin Invest, 1995, 25(10): 746-753.
[17]
Hou L, Shu XO, Gao YT, et al. Anthropometric measurements, physical activity, and the risk of symptomatic gallstone disease in Chinese women [J]. Ann Epidemiol, 2009, 19(5): 344-350.
[18]
Parra-Landazury NM, Cordova-Gallardo J, Méndez-Sánchez N. Obesity and Gallstones [J]. Visc Med, 2021, 37(5): 394-402.
[19]
Hyogo H, Roy S, Cohen DE. Restoration of gallstone susceptibility by leptin in C57BL/6J ob/ob mice [J]. J Lipid Res, 2003, 44(6): 1232-1240.
[20]
Tran KQ, Graewin SJ, Swartz-Basile DA, et al. Leptin-resistant obese mice have paradoxically low biliary cholesterol saturation [J]. Surgery, 2003, 134(2): 372-377.
[21]
Yu DD, Andrali SS, Li H, et al. Novel FXR (farnesoid X receptor) modulators: Potential therapies for cholesterol gallstone disease [J]. Bioorg Med Chem, 2016, 24(18): 3986-3993.
[22]
Hu H, Shao W, Liu Q, et al. Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion [J]. Nat Commun, 2022, 13(1): 252.
[23]
Dittrick GW, Thompson JS, Campos D, et al. Gallbladder pathology in morbid obesity [J]. Obes Surg, 2005, 15(2): 238-242.
[24]
Kim MS, Song M, Kim S, et al. Causal effect of adiposity on the risk of 19 gastrointestinal diseases: a Mendelian randomization study [J]. Obesity (Silver Spring), 2023, 31(5): 1436-1444.
[25]
Yokoe M, Hata J, Takada T, et al. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis (with videos) [J]. J Hepatobiliary Pancreat Sci, 2018, 25(1): 41-54.
[26]
Augustin T, Moslim MA, Brethauer S, et al. Obesity and its implications for morbidity and mortality after cholecystectomy: A matched NSQIP analysis [J]. Am J Surg, 2017, 213(3): 539-543.
[27]
Al-Azzawi HH, Nakeeb A, Saxena R, et al. Cholecystosteatosis: an explanation for increased cholecystectomy rates [J]. J Gastrointest Surg, 2007, 11(7): 835-42; discussion 842-843.
[28]
Goldblatt MI, Swartz-Basile DA, Svatek CL, et al. Decreased gallbladder response in leptin-deficient obese mice [J]. J Gastrointest Surg, 2002, 6(3): 438-442; discussion 443-444.
[29]
Patel SB. Ezetimibe: a novel cholesterol-lowering agent that highlights novel physiologic pathways [J]. Curr Cardiol Rep, 2004, 6(6): 439-442.
[30]
Mathur A, Al-Azzawi HH, Lu D, et al. Steatocholecystitis: the influence of obesity and dietary carbohydrates [J]. J Surg Res, 2008, 147(2): 290-297.
[31]
Tsai CJ. Steatocholecystitis and fatty gallbladder disease [J]. Dig Dis Sci, 2009, 54(9): 1857-1863.
[32]
Hu J, Tang J, Zhang X, et al. Landscape in the gallbladder mycobiome and bacteriome of patients undergoing cholelithiasis with chronic cholecystitis [J]. Front Microbiol, 2023, 14: 1131694.
[33]
Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies [J]. Lancet, 2008, 371(9612): 569-578.
[34]
Larsson SC, Wolk A. Obesity and the risk of gallbladder cancer: a meta-analysis. [J]. British Journal of Cancer, 2007, 96(9): 1457-1461.
[35]
Zatonski WA, Lowenfels AB, Boyle P, et al. Epidemiologic aspects of gallbladder cancer: a case-control study of the SEARCH Program of the International Agency for Research on Cancer [J]. J Natl Cancer Inst, 1997, 89(15): 1132-1138.
[36]
Ryu S, Chang Y, Yun KE, et al. Gallstones and the Risk of Gallbladder Cancer Mortality: A Cohort Study [J]. Am J Gastroenterol, 2016, 111(10): 1476-1487.
[37]
Park J, Morley TS, Kim M, et al. Obesity and cancer--mechanisms underlying tumour progression and recurrence [J]. Nat Rev Endocrinol, 2014, 10(8): 455-465.
[38]
Kitasato A, Tajima Y, Kuroki T, et al. Inflammatory cytokines promote inducible nitric oxide synthase-mediated DNA damage in hamster gallbladder epithelial cells [J]. World J Gastroenterol, 2007, 13(47): 6379-6384.
[39]
Werner H, Bruchim I. The insulin-like growth factor-I receptor as an oncogene [J]. Arch Physiol Biochem, 2009, 115(2): 58-71.
[40]
Wang F, Wang B, Qiao L. Association between obesity and gallbladder cancer [J]. Front Biosci (Landmark Ed), 2012, 17(7): 2550-2558.
[41]
Sharma A, Sharma KL, Gupta A, et al. Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update [J]. World J Gastroenterol, 2017, 23(22): 3978-3998.
[42]
Stender S, Nordestgaard BG, Tybjaerg-Hansen A. Elevated body mass index as a causal risk factor for symptomatic gallstone disease: a Mendelian randomization study [J]. Hepatology, 2013, 58(6): 2133-2141.
[43]
Aronne LJ, Sattar N, Horn DB, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial [J]. JAMA, 2024, 331(1): 38-48.
[44]
Mathus-Vliegen EM, Van Ierland-Van Leeuwen ML, Terpstra A. Lipase inhibition by orlistat: effects on gall-bladder kinetics and cholecystokinin release in obesity [J]. Aliment Pharmacol Ther, 2004, 19(5): 601-611.
[45]
Jonas E, Marsk R, Rasmussen F, et al. Incidence of postoperative gallstone disease after antiobesity surgery: population-based study from Sweden [J]. Surg Obes Relat Dis, 2010, 6(1): 54-58.
[46]
Alsallamin I, Chakhachiro D, Bawwab A, et al. Prevalence of Symptomatic Gallbladder Disease After Bariatric Surgery: A Literature Review [J]. Cureus, 2023, 15(4): e37777.
[47]
Moon RC, Teixeira AF, DuCoin C, et al. Comparison of cholecystectomy cases after Roux-en-Y gastric bypass, sleeve gastrectomy, and gastric banding [J]. Surg Obes Relat Dis, 2014, 10(1): 64-68.
[48]
Erlinger S. Gallstones in obesity and weight loss [J]. Eur J Gastroenterol Hepatol, 2000, 12(12): 1347-1352.
[49]
Veyrie N, Servajean S, Berger N, et al. Gallbladder complications after bariatric surgery[J]. Gastroenterol Clin Biol, 2007, 31(4): 378-384.
[50]
Schauer PR, Burguera B, Ikramuddin S, et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus [J]. Ann Surg, 2003, 238(4): 467-484; discussion 84-85.
[51]
Al-Jiffry BO, Shaffer EA, Saccone GT, et al. Changes in gallbladder motility and gallstone formation following laparoscopic gastric banding for morbid obestity [J]. Can J Gastroenterol, 2003, 17(3): 169-174.
[52]
Jansen PL, van Werven J, Aarts E, et al. Alterations of hormonally active fibroblast growth factors after Roux-en-Y gastric bypass surgery [J]. Dig Dis, 2011, 29(1): 48-51.
[53]
Tiong L, Oh J. Safety and efficacy of a laparoscopic cholecystectomy in the morbid and super obese patients [J]. HPB (Oxford), 2015, 17(7): 600-604.
[54]
Wong A, Naidu S, Lancashire RP, et al. The impact of obesity on outcomes in patients undergoing emergency cholecystectomy for acute cholecystitis [J]. ANZ J Surg, 2022, 92(5): 1091-1096.
[55]
Paajanen H, Käkelä P, Suuronen S, et al. Impact of obesity and associated diseases on outcome after laparoscopic cholecystectomy [J]. Surg Laparosc Endosc Percutan Tech, 2012, 22(6): 509-513.
[56]
Johansson K, Sundström J, Marcus C, et al. Risk of symptomatic gallstones and cholecystectomy after a very-low-calorie diet or low-calorie diet in a commercial weight loss program: 1-year matched cohort study [J]. Int J Obes (Lond), 2014, 38(2): 279-284.
[57]
Sulaberidze G, Okujava M, Liluashvili K, et al. Dietary fiber's benefit for gallstone disease prevention during rapid weight loss in obese patients [J]. Georgian Med News, 2014(231): 95-99.
[58]
Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: cholelithiasis and cancer [J]. Gut Liver, 2012, 6(2): 172-187.
[59]
Banim PJ, Luben RN, Wareham NJ, et al. Physical activity reduces the risk of symptomatic gallstones: a prospective cohort study [J]. Eur J Gastroenterol Hepatol, 2010, 22(8): 983-988.
[60]
Lander EM, Wertheim BC, Koch SM, et al. Vegetable protein intake is associated with lower gallbladder disease risk: Findings from the Women's Health Initiative prospective cohort [J]. Prev Med, 2016, 88: 20-26.
[61]
Uy MC, Talingdan-Te MC, Espinosa WZ, et al. Ursodeoxycholic acid in the prevention of gallstone formation after bariatric surgery: a meta-analysis [J]. Obes Surg, 2008, 18(12): 1532-1538.
[62]
Stokes CS, Gluud LL, Casper M, et al. Ursodeoxycholic acid and diets higher in fat prevent gallbladder stones during weight loss: a meta-analysis of randomized controlled trials [J]. Clin Gastroenterol Hepatol, 2014, 12(7): 1090-1100 e2; quiz e61.
[63]
Méndez-Sánchez N, González V, Aguayo P, et al. Fish oil (n-3) polyunsaturated fatty acids beneficially affect biliary cholesterol nucleation time in obese women losing weight [J]. J Nutr, 2001, 131(9): 2300-2303.
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