Obesity and Non-Alcoholic Fatty Liver Disease: Pathophysiology and Management Focused


  •   . Febyan

  •   Norman Delvano Weky


The continuing rise of obesity epidemic in the global population has been markedly associated with the escalating occurrence and severity of non-alcoholic fatty liver disease (NAFLD). This condition represents a complex metabolic imbalance, primarily characterized by excessive intrahepatic accumulation of triglycerides, known as hepatic steatosis. This pathophysiological process is initiated by the disproportionation between the uptake of dietary fatty acids in plasma, as well as the increase of de novo fatty acid synthesis, which is not equally accompanied by the exportation and oxidation of fatty acid in the form of triglycerides. As mentioned earlier, the underlying metabolic process becomes a significant risk factor for developing cardiometabolic complications, involving type 2 diabetes mellitus, insulin resistance, and dyslipidemia. This review presents a comprehensive understanding of the pathogenesis and pathophysiology of obesity and NAFLD to determine innovative management approaches for the prevention and treatment of the disease.

Keywords: Non-alcoholic fatty liver disease, obesity, lipid, metabolic disorder


Chalasani, N., Younossi, Z., Lavine, J.E., et al., “The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association,” Hepatology, vol. 55, no. 6, pp. 2005-2023, 2012.

Leite, N.C., Araujo, A.L., Villela-Nogueira, C.A., et al., “Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus,” Liver International: Official Journal of the International Association for the Study of the Liver, vol. 29, no. 1, pp. 113-119, 2009.

Ogden, C.L., Carroll, M.D., Kit, B.K., et al., “Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010,” JAMA, vol. 307, no. 5, pp. 483-490, 2012.

Tsigos, C., Hainer, V., Basdevant, A., et al., “Management of obesity in adults: European clinical practice guidelines,” Obesity Facts, vol. 1, no. 2, pp. 106-116, 2008.

Ogden C.L., Carroll M.D., “Prevalence of overweight, obesity, and extreme obesity among adults: United States, trends 1960–1962 through 2007–2008,” National Center for Health Statistics, 2010.

Kim, C.H., Younossi, Z.M., “Non-alcoholic fatty liver disease: a manifestation of the metabolic syndrome,” Cleveland Clinic Journal of Medicine, vol. 75, no. 10, pp. 721-728, 2008.

Younossi, Z.M., “Review article: current management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis,” Aliment Pharmacol Ther., vol. 28, pp. 2-12, 2008.

Ahmed, A., Wong, R.J., Harrison, S.A., “Non-alcoholic fatty liver disease review: Diagnosis, treatment and outcomes,” Clin Gastroenterol Hepatol., vol. 13, pp. 2062-2070, 2015.

Trovato, F.M., Castrogiovanni, P., Szychlinska, M.A., et al., “Early effects of high-fat diet, extra-virgin olive oil and vitamin D in a sedentary rat model of non-alcoholic fatty liver disease,” Histol Histopathol., vol. 33, pp. 1201-1213, 2018.

Cholankeril, G., Patel, R., Khurana, S., et al., “Hepatocellular carcinoma in non-alcoholic steatohepatitis: Current knowledge and implications for management,” World J Hepatol., vol. 9, pp. 533-543, 2017.

Satapathy, S.K., Sanyal, A.J., “Epidemiology and natural history of non-alcoholic fatty liver disease,” Seminars in Liver Disease, vol. 35, no. 3, pp. 1-15, 2015.

Vajro, P., Lenta, S., Socha, P., et al., “Diagnosis of non-alcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee,” JPGN, vol. 54, no. 5, pp. 700-713, 2012.

Divella, R., Mazzocca, A., Daniele, A., et al., “Obesity, non-alcoholic fatty liver disease and adipocytokines network in promotion of cancer,” Int J Biol Sci., vol. 15, no. 3, pp. 610-616, 2019.

Choi, S., Diehl, A., “Hepatic triglyceride synthesis and non-alcoholic fatty liver disease,” Curr Opin Lipidol., vol. 19, pp. 295-300, 2008.

Rector, R.S., Thyfault, J.P., Wei, Y., et al., “Non-alcoholic fatty liver disease and the metabolic syndrome: an update,” World J Gastroenterol, vol. 14, pp. 185-192, 2008.

Combs, T., Berg, A., Obici, S., et al., “Endogenous glucose production is inhibited by the adipose-derived protein Acrp30,” J Clin Invest., vol. 108, pp. 1875-1188, 2001.

Rajala, M., Scherer, P., “Minireview: the adipocyte at the crossroads of energy homeostasis, inflammation, and atherosclerosis,” Endocrinology, vol. 144, pp. 3765-3773, 2003.

Li, Z., Yang, S., Lin, H, et al., “Probiotics and antibodies to TNF inhibit inflammatory activity and improve non-alcoholic fatty liver disease,” Hepatology, vol. 37, pp. 343-359, 2003.

Unger, R., “Lipotoxic diseases,” Annu Rev Med., vol. 53, pp. 319-336, 2002.

Leclercq, I.A., Farrell, G.C., Schriemer, R., et al., “Leptin is essential for the hepatic fibrogenic response to chronic liver injury,” J Hepatol., vol. 27, pp. 206-213, 2002.

Bugianesi, E., McCullough, A., Marchesini, G., “Insulin resistance: A metabolic pathway to chronic liver disease,” Hepatology, vol. 42, pp. 987-1000, 2005.

Jiang, J., Torok, N., “Non-alcoholic steatohepatitis and the metabolic syndrome,” Metab Syndr Relat Disord., vol. 6, pp. 1-8, 2005.

Angulo P., “Non-alcoholic fatty liver disease,” N Engl J Med., vol. 346, pp. 1221-1231, 2002.

Polyzos, S.A., Kountouras, J., Mantzoros, C.S., “Adipose tissue, obesity and non-alcoholic fatty liver disease,” Minerva Endocrinol., vol. 42, pp. 92-108, 2017.

Mota, M., Banini, B.A., Cazanave, S.C., et al., “Molecular mechanisms of lipotoxicity and glucotoxicity in non-alcoholic fatty liver disease,” Metabolism, vol. 65, pp. 1049-1061, 2016.

Tordjman, J., Guerre-Millo, M., Clement, K., “Adipose tissue inflammation and liver pathology in human obesity,” Diabetes Metab., vol. 34, pp. 658-663, 2008.

Nati, M., Haddad, D., Birkenfeld, A.L., et al., “The role of immune cells in metabolism-related liver inflammation and development of non-alcoholic steatohepatitis (NASH),” Rev Endocr Metab Disord., vol. 17, pp. 29-39, 2016.

National Institute for Health and Care Excellence (UK), “Non-alcoholic fatty liver disease: assessment and management,” Available from http://www.niceorg.ukguidanceng49.

Paul, J., Venugopal, R.V., Peter, L., et al., “Effects of lifestyle modification on liver enzyme and Fibroscan in Indian patients with non-alcoholic fatty liver disease,” Gastroenterol Rep., vol. 6, pp. 49-53, 2018.

Saab, S., Mallam, D., Cox, G.A., et al., “Impact of coffee on liver diseases: a systematic review,” Liver Int, vol. 34, pp. 495-504, 2014.

Setiawan, V.W., Porcel, J., Wei, P., et al., “Coffee drinking and alcoholic and non-alcoholic fatty liver diseases and viral hepatitis in the multiethnic cohort,” Clin Gastroenterol Hepatol., vol. 15, no. 8, pp. 1305-1307, 2017.

Wenxia, L., Sainan, L., Jingjing, L., et al., “Effects of omega-3 fatty acid in non-alcoholic fatty liver disease: a meta-analysis,” Gastroenterol Res Pract., vol. 2016, no. 1459790, 2016.

Salomone, F., Galvano, F., Li, V.G., “Molecular bases underlying the hepatoprotective effects of coffee,” Nutrients, vol. 9, no. 1, pp. 85, 2017.

Marchesini, G., Day, C.P., Dufour, J.F., et al., “EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease,” J Hepatol., vol. 64, pp. 1388-1402, 2016.

US Department of Agriculture. Available at: www.choosemyplate.gov; and American Heart Association. Available at: www.heart.org.

Kargulewicz, A., Stankowiak-Kulpa, H., Grzymislawski, M., “Dietary recommendations for patients with non-alcoholic fatty liver disease,” Prz Gastroenterol., vol. 9, no. 1, pp. 18-23, 2014.

Zelber-Sagi, S., Kessler, A., Brazowsky, E., et al., “A double-blind randomized placebo-controlled trial of orlistat for the treatment of non-alcoholic fatty liver disease,” Clin Gastroenterol Hepatol., vol. 4, pp. 639-644, 2006.

Harrison, S.A., Brunt, E.M., Fecht, W.J., et al., “Orlistat for overweight subjects with non-alcoholic steatohepatitis (NASH): a randomized prospective trial,” Hepatology, vol. 49, pp. 80-86, 2009.

Uygun, A., Kadayifci, A., Isik, A.T., et al., “Metformin in the treatment of patients with non-alcoholic steatohepatitis,” Aliment Pharmacol Ther., vol. 19, pp. 537-544, 2004.

Belfort, R., Harrison, S.A., Brown, K., et al., “A placebo-controlled trial of pioglitazone in subjects with non-alcoholic steatohepatitis,” N Engl J Med., vol. 355, pp. 2297-2307, 2006.

Sanyal, A.J., Chalasani, N., Kowdley, K.V., et al., “Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis,” N Engl J Med., vol. 362, pp. 1675-1685, 2010.

Lincoff, A., Wolski, K., Nicholls, S., et al., “Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials,” JAMA, vol. 298, pp. 1180- 1188, 2007.

Harrison, S.A., Torgerson, S., Hayashi, P., et al., “Vitamin E and vitamin C treatment improves fibrosis in patients with non-alcoholic steatohepatitis,” Am J Gastroenterol, vol. 98, pp. 2485-2490, 2003.

Sanyal, A.J., Mofrad, P.S., Contos, M.J., et al., “A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of non-alcoholic steatohepatitis,” Clin Gastroenterol Hepatol., vol. 2, pp. 1107-1115, 2004.

Klein, E.A., Thompson, I.M., Tangen, C.M., et al., “Vitamin E and the risk of prostate cancer. The selenium and vitamin E cancer prevention trial (SELECT),” JAMA, vol. 306, pp. 1549-1556, 2011.

Leushner, U., Lindenthal, B., Herrman, G., et al., “High-dose ursodeoxycholic acid therapy for non-alcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial,” Hepatology, vol. 52, pp. 472-479, 2010.

Ratziu, V., de Ledinghen, V., Oberti, F., et al., “A randomized controlled trial of high-dose ursodeoxycholic acid for non-alcoholic steatohepatitis,” J Hepatol., vol. 54, pp. 1011-1019, 2011.

Spadaro, L., Magliocco, O., Spampinato, D., et al., “Effects of n-3 polyunsaturated fatty acids in subjects with non-alcoholic fatty liver disease,” Dig Liver Dis., vol. 40, pp. 194-199, 2008.

Lewis, J.H., Mortensen, M.E., Zweig, S., et al. in Chronic Liver Disease Study Investigators, “Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial,” Hepatology, vol. 46, no. 5, pp. 1453-1463, 2007.

Nelson, A, Torres, D.M., Morgan, A.E., et al., “A pilot study using simvastatin in the treatment of non-alcoholic steatohepatitis: a randomized placebo-controlled trial,” J Clin Gastroenterol., vol. 43, pp. 990-994, 2009.

Zolfaghari, H., Askari, G., Siassi, F., et al., “Intake of nutrients, fiber, and sugar in patients with non-alcoholic fatty liver disease in comparison to healthy individuals,” Int J Prev Med., vol. 7, no. 98, 2016.

Beilfuss, A., Sowa, J.P., Sydor, S., et al., “Vitamin D counteracts fibrogenic TGF-beta signalling in human hepatic stellate cells both receptor-dependently and independently,” Gut, vol. 64, pp. 791-799, 2015.

Amiri, H.L., Agah, S., Mousavi, S.N., et al., “Regression of non-alcoholic fatty liver by vitamin D supplement: a double-blind randomized controlled clinical trial,” Arch Iran Med, vol. 19, no. 9, pp. 631-638, 2016.


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How to Cite
Febyan, ., & Weky, N. D. (2021). Obesity and Non-Alcoholic Fatty Liver Disease: Pathophysiology and Management Focused. European Journal of Medical and Health Sciences, 3(1), 6-12. https://doi.org/10.24018/ejmed.2021.3.1.645