The decrease in ATP increases oxidative stress and impairments in proper protein synthesis and mitochondrial function in the liver. Insulin resistance
Insulin resistance contributes to the accumulation of toxic fat in the liver in several ways. First, it promotes the release of free fatty acids (FFAs) from adipose tissue into the blood. Typically, adipose tissue stores lipids in the form of triglycerides, slowly releasing them into the bloodstream when insulin is low. In insulin-resistant adipose tissue, such as in people with obesity and type 2 diabetes, more triglycerides are broken down into FFAs and released into the bloodstream, promoting uptake by the liver. Second, insulin promotes the production of new FFAs in the liver via de novo lipogenesis; this production of liver fats continues to be stimulated by insulin, even when other tissues are insulin-resistant. These FFAs are combined back into triglycerides in the liver, forming the major constituent of the accumulated fat in the liver. The three sources of free fatty acids that contribute to liver triglyceride accumulation include FFAs circulating in the bloodstream (59%), FFAs derived from carbohydrates such as fructose and glucose (26%), and diet (14%). Despite the accumulation of triglycerides in the liver, they are not directly toxic to liver tissue.
Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), with the latter also including liver inflammation. Non-alcoholic fatty liver is less dangerous than NASH and usually does not progress to NASH or liver cirrhosis. When NAFL does progress to NASH, it may eventually lead to complications such as cirrhosis, liver cancer, liver failure, or cardiovascular disease.Obesity and type 2 diabetes are strong risk factors for NAFLD. Other risks include being overweight, metabolic syndrome (defined as at least three of the five following medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum HDL cholesterol), a diet high in fructose, and older age. NAFLD and alcoholic liver disease are types of fatty liver disease. Obtaining a sample of the liver after excluding other potential causes of fatty liver can confirm the diagnosis.Treatment for NAFLD is weight loss by dietary changes and exercise. There is tentative evidence for pioglitazone and vitamin E; bariatric surgery can improve or resolve severe cases. Those with NASH have a 2.6% increased risk of dying per year.NAFLD is the most common liver disorder worldwide and is present in approximately 25% of the worlds population. It is also very common in developed nations, such as the United States, and affected about 75 to 100 million Americans in 2017.