Role of glucagon-like peptide-1, chronic inflammation, and atherosclerosis in non-alcoholic fatty liver disease: a cross-sectional observational study_West China Medical Journal

Authors：

DENG Lisha ¹ , DONG Yajie ¹ ^共 , LÜ Qingguo ¹ , WAN Heng ² , LU Yutao ² , XIANG Biying ² , FAN Qiuyan ² ,  TONG Nanwei ¹

1. Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Xi’an Road Community Health Service Center, Chengdu, Sichuan 610072, P. R. China;

Corresponding author：

TONG Nanwei, Email: buddyjun@hotmail.com

Keywords：

Non-alcoholic fatty liver disease; Glucagon-like peptide-1; Atherosclerosis; Chronic inflammation

DOI：

10.7507/1002-0179.201712096

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Objective To investigate and analyze the relationships among glucagon-like peptide-1 (GLP-1) level, chronic inflammation, and atherosclerosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods From October 2016 to February 2017, using cross-sectional investigation, the GLP-1 level, chronic inflammation, and atherosclerosis were investigated in 80 subjects (40 NAFLD patients in NAFLD group, and 40 non-fatty liver disease participants in control group) who underwent physical examination at Xi’an Road Community Hospital. Results Compared with those in the control group, GLP-1 fasting level in patients with NAFLD [(9.09±1.03) vs. (9.15±1.06) pmol/L, P=0.807] and postprandial plasma GLP-1 [(15.96±3.37) vs. (17.46±4.76) pmol/L, P=0.108] had no changes. The correlations of GLP-1 level with chronic inflammation and insulin resistance (IR) were not significant either. The increased risk of carotid intima-media thickness related cardiovascular disease (CVD) in the NAFLD group was greater than that in the control group, and the difference was statistically significant [22 (55.0%)vs.13 (32.5%), P=0.043]. When the plasma lipoprotein-associated phospholipase A2 level increased, the risk of NAFLD increased [odd ratio (OR)=1.16, 95% confidence interval (CI) (1.02, 1.32), P=0.023]. Plasma ceramide kinase (CERK) in the NAFLD group was lower than that in the control group, and the difference was statistically significant [(12.36±2.45) vs. (18.33±3.71) ng/mL, P<0.001]. When the plasma CERK level of the fasting plasma was elevated, the risk of NAFLD decreased [OR=0.30, 95%CI (0.12, 0.78), P=0.014]. The homeostasis model assessment of insulin resistance (HOMA-IR) in the NAFLD group was higher than that in the control group, and the difference was statistically significant (2.46±2.53 vs. 1.11±0.66, P=0.002). The Matsuda index in the NAFLD group was less than that in the control group, and the difference was statistically significant (5.88±4.09 vs. 10.46±7.90, P=0.002). When HOMA-IR increased, the risk of NAFLD increased [OR=2.75, 95%CI (2.49, 3.12), P=0.036]. Conclusions Plasma GLP-1 level is not a sensitive indicator of chronic inflammation and IR in patients with NAFLD. Patients with NAFLD are in an increased risk of atherosclerosis and CVD. It suggests that NAFLD might be involved in chronic inflammation and IR. Chronic inflammation can cause IR, and then chronic inflammation and IR can cause NAFLD and subclinical atherosclerosis. In return for this, NAFLD increases chronic inflammation and IR.

Citation： DENG Lisha, DONG Yajie, LÜ Qingguo, WAN Heng, LU Yutao, XIANG Biying, FAN Qiuyan, TONG Nanwei. Role of glucagon-like peptide-1, chronic inflammation, and atherosclerosis in non-alcoholic fatty liver disease: a cross-sectional observational study. West China Medical Journal, 2018, 33(5): 520-526. doi: 10.7507/1002-0179.201712096 Copy

1.	Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology, 2003, 37(4): 917-923.
2.	Fuchs CD, Claudel T, Trauner M. Role of metabolic lipases and lipolytic metabolites in the pathogenesis of NAFLD. Trends Endocrinol Metab, 2014, 25(11): 576-585.
3.	Fan JG, Li F, Cai XB, et al. The importance of metabolic factors for the increasing prevalence of fatty liver in Shanghai factory workers. J Gastroenterol Hepatol, 2007, 22(5): 663-668.
4.	Fan JG, Zhu J, Li XJ, et al. Prevalence of and risk factors for fatty liver in a general population of Shanghai, China. J Hepatol, 2005, 43(3):508-514.
5.	Liao XH, Cao X, Liu J, et al. Prevalence and features of fatty liver detected by physical examination in Guangzhou. World J Gastroenterol, 2013, 19(32): 5334-5339.
6.	Hamaguchi M, Kojima T, Takeda N, et al. Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol, 2007, 13(10): 1579-1584.
7.	Bril F, Sninsky JJ, Baca AM, et al. Hepatic steatosis and insulin resistance, but not steatohepatitis, promote atherogenic dyslipdemia in NAFLD. J Clin Endocrinol Metab, 2016, 101(2): 644-652.
8.	Everard A, Lazarevic V, Derrien M, et al. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes, 2011, 60(11): 2775-2786.
9.	Cani PD, Osto M, Geurts L, et al. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes, 2012, 3(4): 279-288.
10.	Svegliati-Baroni G, Saccomanno S, Rychlicki C, et al. Glucagon-like peptide-1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high-fat diet in nonalcoholic steatohepatitis. Liver Int, 2011, 31(9): 1285-1297.
11.	Bozzetto L, Annuzzi G, Ragucci M, et al. Insulin resistance, postprandial GLP-1 and adaptive immunity are the main predictors of NAFLD in a homogeneous population at high cardiovascular risk. Nutr Metab Cardiovasc Dis, 2016, 26(7): 623-629.
12.	Dong Y, Lv Q, Li S, et al. Efficacy and safety of glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol, 2017, 41(3): 284-295.
13.	Bernsmeier C, Meyer-Gerspach AC, Blaser LS, et al. Glucose-induced glucagon-like peptide 1 secretion is deficient in patients with non-alcoholic fatty liver disease. PloS One, 2014, 9(1): e87488.
14.	Kullman EL, Kelly KR, Haus JM, et al. Short-term aerobic exercise training improves gut peptide regulation in nonalcoholic fatty liver disease. J Appl Physiol (1985), 2016, 120(10): 1159-1164.
15.	Farrell GC, Chitturi S, Lau GK, et al. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary. J Gastroenterol Hepatol, 2007, 22(6): 775-777.
16.	World Health Organization. WHO expert consultation on waist circumference and waist-hip ratio. (2008-12-11)[2018-04-08]. http://www.who.int/nutrition/topics/expert_consultation_wc_whr/en/.
17.	Ashwell M, Gunn P, Gibson S. Waist-to-height ratio is a better screening tool than waist circumference and BMI for adult cardiometabolic risk factors: systemic review and meta-analysis. Obes Rev, 2012, 13(3): 275-286.
18.	Liu Y, Tong G, Tong W, et al. Can body mass index, waist circumference, waist-hip ratio and waist-height ratio predict the presence of multiple metabolic risk factors in Chinese subjects?. BMC Public Health, 2011, 11: 35.
19.	Browning LM, Hsieh SD, Ashwell M. A systemic review of waist-to-height ratio as a screening tool for the prediction of cardiovascular disease and diabetes: 0.5 could be a suitable global boundary value. Nutr Res Rev, 2010, 23(2): 247-269.
20.	Jung S, Kim OY, Kim M, et al. Age-related increase in alanine aminotransferase correlates with elevated levels of plasma amino acids, decanoylcarnitine, Lp-PLA2 activity, oxidative stress, and arterial stiffness. J Proteome Res, 2014, 13(7): 3467-3475.
21.	Bornancin F. Ceramide kinase: the first decade. Cell Signal, 2011, 23(6): 999-1008.
22.	DeFronzo RA, Matsuda M. Reduced time points to calculate the composite index. Diabetes Care, 2010, 33(7): e93.
23.	中华人民共和国国家质量监督检验检疫总局, 中国国家标准化管理委员会. WS/T 428－2013 成人体重判定. 北京: 中国标准出版社, 2013: 1-2.
24.	翁建平. 中国2型糖尿病防治指南(四). 中国社区医师, 2011(46): 9-12.
25.	Stein JH, Korcarz CE, Hurst RT, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascula. J Am Soc Echocardiogr, 2008, 21(2): 93-111.
26.	Ao N, Yang J, Wang X, et al. Glucagon-like peptide-1 preserves non-alcoholic fatty liver disease through inhibition of the endoplasmic reticulum stress-associated pathway. Hepatol Res, 2016, 46(4): 343-353.
27.	Tilg H, Moschen AR. Insulin resistance, inflammation and non-alcoholic fatty liver disease. Trends Endocrinol Metab, 2008, 19(10): 371-379.
28.	Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med, 2016, 374(14): 1321-1331.
29.	Ratziu V, Giral P, Jacqueminet S, et al. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology, 2008, 135(1): 100-110.

1. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology, 2003, 37(4): 917-923.
2. Fuchs CD, Claudel T, Trauner M. Role of metabolic lipases and lipolytic metabolites in the pathogenesis of NAFLD. Trends Endocrinol Metab, 2014, 25(11): 576-585.
3. Fan JG, Li F, Cai XB, et al. The importance of metabolic factors for the increasing prevalence of fatty liver in Shanghai factory workers. J Gastroenterol Hepatol, 2007, 22(5): 663-668.
4. Fan JG, Zhu J, Li XJ, et al. Prevalence of and risk factors for fatty liver in a general population of Shanghai, China. J Hepatol, 2005, 43(3):508-514.
5. Liao XH, Cao X, Liu J, et al. Prevalence and features of fatty liver detected by physical examination in Guangzhou. World J Gastroenterol, 2013, 19(32): 5334-5339.
6. Hamaguchi M, Kojima T, Takeda N, et al. Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol, 2007, 13(10): 1579-1584.
7. Bril F, Sninsky JJ, Baca AM, et al. Hepatic steatosis and insulin resistance, but not steatohepatitis, promote atherogenic dyslipdemia in NAFLD. J Clin Endocrinol Metab, 2016, 101(2): 644-652.
8. Everard A, Lazarevic V, Derrien M, et al. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes, 2011, 60(11): 2775-2786.
9. Cani PD, Osto M, Geurts L, et al. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes, 2012, 3(4): 279-288.
10. Svegliati-Baroni G, Saccomanno S, Rychlicki C, et al. Glucagon-like peptide-1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high-fat diet in nonalcoholic steatohepatitis. Liver Int, 2011, 31(9): 1285-1297.
11. Bozzetto L, Annuzzi G, Ragucci M, et al. Insulin resistance, postprandial GLP-1 and adaptive immunity are the main predictors of NAFLD in a homogeneous population at high cardiovascular risk. Nutr Metab Cardiovasc Dis, 2016, 26(7): 623-629.
12. Dong Y, Lv Q, Li S, et al. Efficacy and safety of glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol, 2017, 41(3): 284-295.
13. Bernsmeier C, Meyer-Gerspach AC, Blaser LS, et al. Glucose-induced glucagon-like peptide 1 secretion is deficient in patients with non-alcoholic fatty liver disease. PloS One, 2014, 9(1): e87488.
14. Kullman EL, Kelly KR, Haus JM, et al. Short-term aerobic exercise training improves gut peptide regulation in nonalcoholic fatty liver disease. J Appl Physiol (1985), 2016, 120(10): 1159-1164.
15. Farrell GC, Chitturi S, Lau GK, et al. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary. J Gastroenterol Hepatol, 2007, 22(6): 775-777.
16. World Health Organization. WHO expert consultation on waist circumference and waist-hip ratio. (2008-12-11)[2018-04-08]. http://www.who.int/nutrition/topics/expert_consultation_wc_whr/en/.
17. Ashwell M, Gunn P, Gibson S. Waist-to-height ratio is a better screening tool than waist circumference and BMI for adult cardiometabolic risk factors: systemic review and meta-analysis. Obes Rev, 2012, 13(3): 275-286.
18. Liu Y, Tong G, Tong W, et al. Can body mass index, waist circumference, waist-hip ratio and waist-height ratio predict the presence of multiple metabolic risk factors in Chinese subjects?. BMC Public Health, 2011, 11: 35.
19. Browning LM, Hsieh SD, Ashwell M. A systemic review of waist-to-height ratio as a screening tool for the prediction of cardiovascular disease and diabetes: 0.5 could be a suitable global boundary value. Nutr Res Rev, 2010, 23(2): 247-269.
20. Jung S, Kim OY, Kim M, et al. Age-related increase in alanine aminotransferase correlates with elevated levels of plasma amino acids, decanoylcarnitine, Lp-PLA2 activity, oxidative stress, and arterial stiffness. J Proteome Res, 2014, 13(7): 3467-3475.
21. Bornancin F. Ceramide kinase: the first decade. Cell Signal, 2011, 23(6): 999-1008.
22. DeFronzo RA, Matsuda M. Reduced time points to calculate the composite index. Diabetes Care, 2010, 33(7): e93.
23. 中华人民共和国国家质量监督检验检疫总局, 中国国家标准化管理委员会. WS/T 428－2013 成人体重判定. 北京: 中国标准出版社, 2013: 1-2.
24. 翁建平. 中国2型糖尿病防治指南(四). 中国社区医师, 2011(46): 9-12.
25. Stein JH, Korcarz CE, Hurst RT, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascula. J Am Soc Echocardiogr, 2008, 21(2): 93-111.
26. Ao N, Yang J, Wang X, et al. Glucagon-like peptide-1 preserves non-alcoholic fatty liver disease through inhibition of the endoplasmic reticulum stress-associated pathway. Hepatol Res, 2016, 46(4): 343-353.
27. Tilg H, Moschen AR. Insulin resistance, inflammation and non-alcoholic fatty liver disease. Trends Endocrinol Metab, 2008, 19(10): 371-379.
28. Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med, 2016, 374(14): 1321-1331.
29. Ratziu V, Giral P, Jacqueminet S, et al. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology, 2008, 135(1): 100-110.

West China Medical Journal

Role of glucagon-like peptide-1, chronic inflammation, and atherosclerosis in non-alcoholic fatty liver disease: a cross-sectional observational study

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