Lipid metabolism in atrial fibrillation and its current research status_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LV Mengwei ^1,2 , LI Tao ³ , QIAN Yongjun ³ ,  ZHANG Yangyang ¹

1. Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, P.R.China;
2. Shanghai East Hospital of Clinical Medical College, Nanjing Medical University, Shanghai, 200120, P.R.China;
3. Department of Cardiovascular Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;

Corresponding author：

ZHANG Yangyang, Email: zhangyangyang_wy@vip.sina.com

Keywords：

Atrial fibrillation; lipid metabolism; metabolic remodeling; diagnosis and treatment; review

DOI：

10.7507/1007-4848.202010001

Video：

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Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. The metabolic changes of atrial myocytes, especially lipid metabolism, have a significant impact on the electrical signals and structural remodeling of atrial tissue, and play an important role in the occurrence and development of AF. The reduction of fatty acid oxidation ratio and increased aerobic glycolysis ratio are characteristic changes of tissue metabolic remodeling in AF. In this review, we will introduce the latest research status of lipid metabolism in AF from aspects of AF metabolism, clinical treatment and diagnosis and prognosis.

Citation： LV Mengwei, LI Tao, QIAN Yongjun, ZHANG Yangyang. Lipid metabolism in atrial fibrillation and its current research status. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2021, 28(11): 1371-1375. doi: 10.7507/1007-4848.202010001 Copy

1.	Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J, 2016, 37(38): 2893-2962.
2.	Opacic D, van Bragt KA, Nasrallah HM, et al. Atrial metabolism and tissue perfusion as determinants of electrical and structural remodelling in atrial fibrillation. Cardiovasc Res, 2016, 109(4): 527-541.
3.	Homan EA, Reyes MV, Hickey KT, et al. Clinical overview of obesity and diabetes mellitus as risk factors for atrial fibrillation and sudden cardiac death. Front Physiol, 2019, 9: 1847.
4.	Floriani C, Gencer B, Collet TH, et al. Subclinical thyroid dysfunction and cardiovascular diseases: 2016 update. Eur Heart J, 2018, 39(7): 503-507.
5.	Tu T, Zhou S, Liu Z, et al. Quantitative proteomics of changes in energy metabolism-related proteins in atrial tissue from valvular disease patients with permanent atrial fibrillation. Circ J, 2014, 78(4): 993-1001.
6.	Liu Y, Bai F, Liu N, et al. The Warburg effect: A new insight into atrial fibrillation. Clin Chim Acta, 2019, 499: 4-12.
7.	Bertero E, Maack C. Metabolic remodelling in heart failure. Nat Rev Cardiol, 2018, 15(8): 457-470.
8.	Liu Y, Bai F, Liu N, et al. Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation. BMC Cardiovasc Disord, 2020, 20(1): 50.
9.	Steinbusch LK, Schwenk RW, Ouwens DM, et al. Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes. Cell Mol Life Sci, 2011, 68(15): 2525-2538.
10.	Kolwicz SC, Tian R. Glucose metabolism and cardiac hypertrophy. Cardiovasc Res, 2011, 90(2): 194-201.
11.	Harada M, Nattel SN, Nattel S. AMP-activated protein kinase: Potential role in cardiac electrophysiology and arrhythmias. Circ Arrhythm Electrophysiol, 2012, 5(4): 860-867.
12.	Harada M, Tadevosyan A, Qi X, et al. Atrial fibrillation activates amp-dependent protein kinase and its regulation of cellular calcium handling: Potential role in metabolic adaptation and prevention of progression. J Am Coll Cardiol, 2015, 66(1): 47-58.
13.	Hu HJ, Zhang C, Tang ZH, et al. Regulating the Warburg effect on metabolic stress and myocardial fibrosis remodeling and atrial intracardiac waveform activity induced by atrial fibrillation. Biochem Biophys Res Commun, 2019, 516(3): 653-660.
14.	Faubert B, Boily G, Izreig S, et al. AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell Metab, 2013, 17(1): 113-124.
15.	Abed HS, Samuel CS, Lau DH, et al. Obesity results in progressive atrial structural and electrical remodeling: Implications for atrial fibrillation. Heart Rhythm, 2013, 10(1): 90-100.
16.	Verma SK, Krishnamurthy P, Barefield D, et al. Interleukin-10 treatment attenuates pressure overload-induced hypertrophic remodeling and improves heart function via signal transducers and activators of transcription 3-dependent inhibition of nuclear factor-κB. Circulation, 2012, 126(4): 418-429.
17.	Lee HC, Lin YH. The pathogenic role of very low density lipoprotein on atrial remodeling in the metabolic syndrome. Int J Mol Sci, 2020, 21(3): 891.
18.	Lee HC, Chen CC, Tsai WC, et al. Very-low-density lipoprotein of metabolic syndrome modulates gap junctions and slows cardiac conduction. Sci Rep, 2017, 7(1): 12050.
19.	Liu GZ, Hou TT, Yuan Y, et al. Fenofibrate inhibits atrial metabolic remodelling in atrial fibrillation through PPAR-α/sirtuin 1/PGC-1α pathway. Br J Pharmacol, 2016, 173(6): 1095-1109.
20.	Bell DSH, Goncalves E. Atrial fibrillation and type 2 diabetes: Prevalence, etiology, pathophysiology and effect of anti-diabetic therapies. Diabetes Obes Metab, 2019, 21(2): 210-217.
21.	Shimano M, Tsuji Y, Inden Y, et al. Pioglitazone, a peroxisome proliferator-activated receptor-gamma activator, attenuates atrial fibrosis and atrial fibrillation promotion in rabbits with congestive heart failure. Heart Rhythm, 2008, 5(3): 451-459.
22.	Xu D, Murakoshi N, Igarashi M, et al. PPAR-γ activator pioglitazone prevents age-related atrial fibrillation susceptibility by improving antioxidant capacity and reducing apoptosis in a rat model. J Cardiovasc Electrophysiol, 2012, 23(2): 209-217.
23.	Nolly MB, Caldiz CI, Yeves AM, et al. The signaling pathway for aldosterone-induced mitochondrial production of superoxide anion in the myocardium. J Mol Cell Cardiol, 2014, 67: 60-68.
24.	Reil JC, Hohl M, Selejan S, et al. Aldosterone promotes atrial fibrillation. Eur Heart J, 2012, 33(16): 2098-2108.
25.	Takemoto Y, Ramirez RJ, Kaur K, et al. Eplerenone reduces atrial fibrillation burden without preventing atrial electrical remodeling. J Am Coll Cardiol, 2017, 70(23): 2893-2905.
26.	Jie QQ, Li G, Duan JB, et al. Remodeling of myocardial energy and metabolic homeostasis in a sheep model of persistent atrial fibrillation. Biochem Biophys Res Commun, 2019, 517(1): 8-14.
27.	Wang R, Yi X, Li X, et al. Fibroblast growth factor-21 is positively associated with atrial fibrosis in atrial fibrillation patients with rheumatic heart disease. Int J Clin Exp Pathol, 2015, 8(11): 14901-14908.
28.	Han X, Chen C, Cheng G, et al. Serum fibroblast growth factor 21 levels are increased in atrial fibrillation patients. Cytokine, 2015, 73(1): 176-180.
29.	Han SH, Quon MJ, Kim JA, et al. Adiponectin and cardiovascular disease: Response to therapeutic interventions. J Am Coll Cardiol, 2007, 49(5): 531-538.
30.	Choi BJ, Heo JH, Choi IS, et al. Hypoadiponectinemia in patients with paroxysmal atrial fibrillation. Korean Circ J, 2012, 42(10): 668-673.
31.	Golaszewska K, Harasim-Symbor E, Polak-Iwaniuk A, et al. Serum fatty acid binding proteins as a potential biomarker in atrial fibrillation. J Physiol Pharmacol, 2019, 70(1): 25-35.
32.	Rader F, Pujara AC, Pattakos G, et al. Perioperative heart-type fatty acid binding protein levels in atrial fibrillation after cardiac surgery. Heart Rhythm, 2013, 10(2): 153-157.
33.	Malik V, Kale SC, Chowdhury UK, et al. Myocardial injury in coronary artery bypass grafting: On-pump versus off-pump comparison by measuring heart-type fatty-acid-binding protein release. Tex Heart Inst J, 2006, 33(3): 321-327.

1. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J, 2016, 37(38): 2893-2962.
2. Opacic D, van Bragt KA, Nasrallah HM, et al. Atrial metabolism and tissue perfusion as determinants of electrical and structural remodelling in atrial fibrillation. Cardiovasc Res, 2016, 109(4): 527-541.
3. Homan EA, Reyes MV, Hickey KT, et al. Clinical overview of obesity and diabetes mellitus as risk factors for atrial fibrillation and sudden cardiac death. Front Physiol, 2019, 9: 1847.
4. Floriani C, Gencer B, Collet TH, et al. Subclinical thyroid dysfunction and cardiovascular diseases: 2016 update. Eur Heart J, 2018, 39(7): 503-507.
5. Tu T, Zhou S, Liu Z, et al. Quantitative proteomics of changes in energy metabolism-related proteins in atrial tissue from valvular disease patients with permanent atrial fibrillation. Circ J, 2014, 78(4): 993-1001.
6. Liu Y, Bai F, Liu N, et al. The Warburg effect: A new insight into atrial fibrillation. Clin Chim Acta, 2019, 499: 4-12.
7. Bertero E, Maack C. Metabolic remodelling in heart failure. Nat Rev Cardiol, 2018, 15(8): 457-470.
8. Liu Y, Bai F, Liu N, et al. Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation. BMC Cardiovasc Disord, 2020, 20(1): 50.
9. Steinbusch LK, Schwenk RW, Ouwens DM, et al. Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes. Cell Mol Life Sci, 2011, 68(15): 2525-2538.
10. Kolwicz SC, Tian R. Glucose metabolism and cardiac hypertrophy. Cardiovasc Res, 2011, 90(2): 194-201.
11. Harada M, Nattel SN, Nattel S. AMP-activated protein kinase: Potential role in cardiac electrophysiology and arrhythmias. Circ Arrhythm Electrophysiol, 2012, 5(4): 860-867.
12. Harada M, Tadevosyan A, Qi X, et al. Atrial fibrillation activates amp-dependent protein kinase and its regulation of cellular calcium handling: Potential role in metabolic adaptation and prevention of progression. J Am Coll Cardiol, 2015, 66(1): 47-58.
13. Hu HJ, Zhang C, Tang ZH, et al. Regulating the Warburg effect on metabolic stress and myocardial fibrosis remodeling and atrial intracardiac waveform activity induced by atrial fibrillation. Biochem Biophys Res Commun, 2019, 516(3): 653-660.
14. Faubert B, Boily G, Izreig S, et al. AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell Metab, 2013, 17(1): 113-124.
15. Abed HS, Samuel CS, Lau DH, et al. Obesity results in progressive atrial structural and electrical remodeling: Implications for atrial fibrillation. Heart Rhythm, 2013, 10(1): 90-100.
16. Verma SK, Krishnamurthy P, Barefield D, et al. Interleukin-10 treatment attenuates pressure overload-induced hypertrophic remodeling and improves heart function via signal transducers and activators of transcription 3-dependent inhibition of nuclear factor-κB. Circulation, 2012, 126(4): 418-429.
17. Lee HC, Lin YH. The pathogenic role of very low density lipoprotein on atrial remodeling in the metabolic syndrome. Int J Mol Sci, 2020, 21(3): 891.
18. Lee HC, Chen CC, Tsai WC, et al. Very-low-density lipoprotein of metabolic syndrome modulates gap junctions and slows cardiac conduction. Sci Rep, 2017, 7(1): 12050.
19. Liu GZ, Hou TT, Yuan Y, et al. Fenofibrate inhibits atrial metabolic remodelling in atrial fibrillation through PPAR-α/sirtuin 1/PGC-1α pathway. Br J Pharmacol, 2016, 173(6): 1095-1109.
20. Bell DSH, Goncalves E. Atrial fibrillation and type 2 diabetes: Prevalence, etiology, pathophysiology and effect of anti-diabetic therapies. Diabetes Obes Metab, 2019, 21(2): 210-217.
21. Shimano M, Tsuji Y, Inden Y, et al. Pioglitazone, a peroxisome proliferator-activated receptor-gamma activator, attenuates atrial fibrosis and atrial fibrillation promotion in rabbits with congestive heart failure. Heart Rhythm, 2008, 5(3): 451-459.
22. Xu D, Murakoshi N, Igarashi M, et al. PPAR-γ activator pioglitazone prevents age-related atrial fibrillation susceptibility by improving antioxidant capacity and reducing apoptosis in a rat model. J Cardiovasc Electrophysiol, 2012, 23(2): 209-217.
23. Nolly MB, Caldiz CI, Yeves AM, et al. The signaling pathway for aldosterone-induced mitochondrial production of superoxide anion in the myocardium. J Mol Cell Cardiol, 2014, 67: 60-68.
24. Reil JC, Hohl M, Selejan S, et al. Aldosterone promotes atrial fibrillation. Eur Heart J, 2012, 33(16): 2098-2108.
25. Takemoto Y, Ramirez RJ, Kaur K, et al. Eplerenone reduces atrial fibrillation burden without preventing atrial electrical remodeling. J Am Coll Cardiol, 2017, 70(23): 2893-2905.
26. Jie QQ, Li G, Duan JB, et al. Remodeling of myocardial energy and metabolic homeostasis in a sheep model of persistent atrial fibrillation. Biochem Biophys Res Commun, 2019, 517(1): 8-14.
27. Wang R, Yi X, Li X, et al. Fibroblast growth factor-21 is positively associated with atrial fibrosis in atrial fibrillation patients with rheumatic heart disease. Int J Clin Exp Pathol, 2015, 8(11): 14901-14908.
28. Han X, Chen C, Cheng G, et al. Serum fibroblast growth factor 21 levels are increased in atrial fibrillation patients. Cytokine, 2015, 73(1): 176-180.
29. Han SH, Quon MJ, Kim JA, et al. Adiponectin and cardiovascular disease: Response to therapeutic interventions. J Am Coll Cardiol, 2007, 49(5): 531-538.
30. Choi BJ, Heo JH, Choi IS, et al. Hypoadiponectinemia in patients with paroxysmal atrial fibrillation. Korean Circ J, 2012, 42(10): 668-673.
31. Golaszewska K, Harasim-Symbor E, Polak-Iwaniuk A, et al. Serum fatty acid binding proteins as a potential biomarker in atrial fibrillation. J Physiol Pharmacol, 2019, 70(1): 25-35.
32. Rader F, Pujara AC, Pattakos G, et al. Perioperative heart-type fatty acid binding protein levels in atrial fibrillation after cardiac surgery. Heart Rhythm, 2013, 10(2): 153-157.
33. Malik V, Kale SC, Chowdhury UK, et al. Myocardial injury in coronary artery bypass grafting: On-pump versus off-pump comparison by measuring heart-type fatty-acid-binding protein release. Tex Heart Inst J, 2006, 33(3): 321-327.

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