Overweight & Fatty Liver

In the United States non-alcoholic fatty liver disease (NAFLD) affects approximately 30% of adults and is the most common form of liver disease and comprises most of the chronic liver disorders worldwide (Westfall et al., 2020). Typically asymptomatic, NAFLD is a hepatic indicator of metabolic syndrome with intensifying prevalence that equals the escalation in diabetes and obesity (Jensen et al., 2018). NAFLD is closely connected with cardiovascular disease, obesity, and type 2 diabetes.

Previously NAFLD was believed to have resulted from a sedentary lifestyle and overconsumption of processed foods. Current research findings implicate diets high in refined sugar from high-fructose corn syrup (HFCS) and sucrose increasing the prevalence of NAFLD and non-alcoholic steatohepatitis (NASH) (Jensen et al., 2018).

NAFLD manifests as simple steatosis to fulminant NASH, fibrosis, and deteriorating to cirrhosis, and then hepatocellular carcinoma (Fang et al., 2021; Liu et al., 2020). Technically, non-alcoholic fatty liver disease is a series of diseases, involving excessive lipid deposition in the liver and is often comorbid with abnormal blood pressure, diabetes, dyslipidemia, obesity, and other metabolic disorders (Rong et al., 2022).

Individuals exhibiting elevated liver enzymes or hepatic steatosis on abdominal imaging should be suspected of having NAFLD (Westfall et al., 2020). Laboratory findings of NAFLD demonstrate an accumulation of liver triacylglycerols (steatosis) and is marked by infiltration of hepatic fat deposits of > 5% by liver weight or >5% of hepatocytes filled with large fatty vacuoles. In approximately one fourth of affected individuals, fatty liver deposits rise as liver inflammation morphs into non-alcoholic steatohepatitis (NASH) (Jennison et al., 2019).

Researchers Samuel and Shulman (2018) report NAFLD is intertwined with hepatic insulin resistance. Buildup of hepatic diacylglycerol triggers PKC-ε, damaging insulin-stimulated glycogen synthesis and insulin receptor activation. Peripheral insulin resistance circuitously influences lipid metabolism and hepatic glucose via increasing fluctuation of substrates that promote gluconeogenesis (glycerol and fatty acid-derived acetyl-CoA, an allosteric activator of pyruvate carboxylase) and glucose and fatty acids (aka lipogenesis). Fang et al. (2021) claim microRNAs (miRNAs), significant epigenetic features, were recently found to add to NAFLD pathogenesis. Important factors that contribute to the occurrence and progression of NAFLD and its roles in miRNAs include apoptosis, fibrosis, hepatic stellate cell activation, inflammation, insulin resistance, lipid metabolism, and oxidative stress.

Because the origin of NAFLD is multifactorial, traditional

medication therapies predominantly focus on pathogenic aspects. Typical NAFLD interventions concentrate on protecting the liver via regulation of glucose, lipid metabolism, and anti-inflammation. Newer NAFLD interventions are addressing the enterohepatic axis and gastrointestinal microbiome dysregulation (Rong et al., 2022).

One primary NAFLD treatment stresses weight loss through diet and exercise. Healthy weight loss occurs by incorporating healthier lifestyle behaviors which increase regular physical activity and pattern eating selections after the Mediterranean diet. These subtle changes are evidenced based interventions that have helped persons with NAFLD reverse the progression (Zelber-Sagi & Moore, 2024).

Papadopoulos et al. (2023) agrees one common dietary ingredient implicated in contributing to the exacerbation of NAFLD is the prevalence of High-Fructose Corn Syrup (HFCS), an ingredient, which is extensively used in processed foods and beverages of the western diet. Regular consumption of HFCS is correlated to the development and advancement of NAFLD. A mouse study discovered HFCS significantly contributed to steatosis intensification during obesity-related NAFLD, probably stemming from DNL upregulation, together with TCA cycle overactivation and worsening hepatic insulin resistance (Papadopoulos et al., 2023).

Researchers believe macronutrient structure, food selections, and timing of eating can be customized to culture, financial circumstances, and personal preferences. Prescribed NAFLD dietary interventions exclude processed foods and meats, refined carbohydrates, sugar, and saturated fat. These diets are higher in fruits, legumes, nuts, seeds, vegetables, whole grains, lean meats and fish and include healthy fats, high fiber, minerals, polyphenols, and vitamins (Zelber-Sagi & Moore, 2024).

Other treatments can include bariatric surgery, vitamin E supplementation, and pharmacologic therapy (glucagon-like peptide-1 analogues and/or thiazolidinediones) which have shown some promise, but data is limited, and these therapies are not first line (Westfall et al., 2020). Zelber-Sagi and Moore (2024) reports physical activity can autonomously improve steatosis, avert fibrosis and cirrhosis, and decrease mortality.

References

Fang, Z., Dou, G., & Wang, L. (2021). MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease. International Journal of Biological Sciences, 17(7), 1851–1863. https://doi.org/10.7150/ijbs.59588

Jennison, E., Patel, J., Scorletti, E., & Byrne, C. D. (2019). Diagnosis and management of non-alcoholic fatty liver disease. Postgraduate Medical Journal, 95(1124), 314–322. https://doi.org/10.1136/postgradmedj-2018-136316

Jensen, T., Abdelmalek, M. F., Sullivan, S., Nadeau, K. J., Green, M., Roncal, C., Nakagawa, T., Kuwabara, M., Sato, Y., Kang, D.-H., Tolan, D. R., Sanchez-Lozada, L. G., Rosen, H. R., Lanaspa, M. A., Diehl, A. M., & Johnson, R. J. (2018). Fructose and sugar: A major mediator of non-alcoholic fatty liver disease. Journal of Hepatology, 68(5), 1063–1075. https://doi.org/10.1016/j.jhep.2018.01.019

Liu, X., Chen, S., & Zhang, L. (2020). Downregulated microRNA-130b-5p prevents lipid accumulation and insulin resistance in a murine model of nonalcoholic fatty liver disease. American Journal of Physiology. Endocrinology and Metabolism, 319(1), E34–E42. https://doi.org/10.1152/ajpendo.00528.2019

Papadopoulos, G., Legaki, A.-I., Georgila, K., Vorkas, P., Giannousi, E., Stamatakis, G., Moustakas, I. I., Petrocheilou, M., Pyrina, I., Gercken, B., Kassi, E., Chavakis, T., Pateras, I. S., Panayotou, G., Gika, H., Samiotaki, M., Eliopoulos, A. G., & Chatzigeorgiou, A. (2023). Integrated omics analysis for characterization of the contribution of high fructose corn syrup to non-alcoholic fatty liver disease in obesity. Metabolism, 144, 155552. https://doi.org/10.1016/j.metabol.2023.155552

Rong, L., Zou, J., Ran, W., Qi, X., Chen, Y., Cui, H., & Guo, J. (2022). Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD). Frontiers in Endocrinology, 13, 1087260. https://doi.org/10.3389/fendo.2022.1087260

Samuel, V. T., & Shulman, G. I. (2018). Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases. Cell Metabolism, 27(1), 22–41. https://doi.org/10.1016/j.cmet.2017.08.002

Westfall, E., Jeske, R., & Bader, A. R. (2020). Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management. American Family Physician, 102(10), 603–612. https://pubmed.ncbi.nlm.nih.gov/33179890/

Zelber-Sagi, S., & Moore, J. B. (2024). Practical Lifestyle Management of Nonalcoholic Fatty Liver Disease for Busy Clinicians. Diabetes Spectrum: A Publication of the American Diabetes Association, 37(1), 39–47. https://doi.org/10.2337/dsi23-0009