Nonalcoholic fatty liver disease (NAFLD) is a growing health issue affecting one-third of adults and increasing numbers of children in developed countries. It begins with the accumulation of triglycerides (TGs) in the liver, which can lead to inflammation, cirrhosis, and liver cancer. Although NAFLD is linked to obesity and insulin resistance, its causes and treatments remain unclear. Recent research, particularly from human genetic and metabolic studies, has provided new insights into the mechanisms of NAFLD. TGs are stored in adipose tissue and are mobilized under specific conditions, such as in migratory birds. In humans, excessive calorie intake can lead to fatty liver, which is maladaptive and can have severe consequences. NAFLD encompasses a range of liver disorders, starting with hepatic steatosis (fat accumulation in liver cells) and progressing to nonalcoholic steatohepatitis (NASH), which involves inflammation and fibrosis, and eventually cirrhosis. Cirrhosis can lead to liver cancer. The accumulation of TG in the liver is influenced by dietary intake, de novo lipogenesis, and adipose tissue. Factors such as obesity, insulin resistance, and fructose consumption contribute to NAFLD. Genetic studies have identified variants, such as the PNPLA3-I148M mutation, that are associated with increased hepatic TG content and NAFLD risk. These genetic factors can influence the progression of NAFLD to NASH and cirrhosis. NAFLD is influenced by gender, ethnicity, and other genetic factors. While obesity and insulin resistance are major risk factors, other factors also contribute to the disease. The PNPLA3 gene variant is strongly associated with NAFLD and affects the progression of the disease. However, the relationship between hepatic TG accumulation and insulin resistance remains unclear. Animal models have provided insights into the mechanisms of NAFLD, but human studies are essential for understanding the disease. The progression of NAFLD to cirrhosis and liver cancer is a major concern, especially in children. Current treatments include bariatric surgery, diet, and lifestyle changes, which can improve liver health. However, more research is needed to develop effective therapies and improve early detection methods for NAFLD.Nonalcoholic fatty liver disease (NAFLD) is a growing health issue affecting one-third of adults and increasing numbers of children in developed countries. It begins with the accumulation of triglycerides (TGs) in the liver, which can lead to inflammation, cirrhosis, and liver cancer. Although NAFLD is linked to obesity and insulin resistance, its causes and treatments remain unclear. Recent research, particularly from human genetic and metabolic studies, has provided new insights into the mechanisms of NAFLD. TGs are stored in adipose tissue and are mobilized under specific conditions, such as in migratory birds. In humans, excessive calorie intake can lead to fatty liver, which is maladaptive and can have severe consequences. NAFLD encompasses a range of liver disorders, starting with hepatic steatosis (fat accumulation in liver cells) and progressing to nonalcoholic steatohepatitis (NASH), which involves inflammation and fibrosis, and eventually cirrhosis. Cirrhosis can lead to liver cancer. The accumulation of TG in the liver is influenced by dietary intake, de novo lipogenesis, and adipose tissue. Factors such as obesity, insulin resistance, and fructose consumption contribute to NAFLD. Genetic studies have identified variants, such as the PNPLA3-I148M mutation, that are associated with increased hepatic TG content and NAFLD risk. These genetic factors can influence the progression of NAFLD to NASH and cirrhosis. NAFLD is influenced by gender, ethnicity, and other genetic factors. While obesity and insulin resistance are major risk factors, other factors also contribute to the disease. The PNPLA3 gene variant is strongly associated with NAFLD and affects the progression of the disease. However, the relationship between hepatic TG accumulation and insulin resistance remains unclear. Animal models have provided insights into the mechanisms of NAFLD, but human studies are essential for understanding the disease. The progression of NAFLD to cirrhosis and liver cancer is a major concern, especially in children. Current treatments include bariatric surgery, diet, and lifestyle changes, which can improve liver health. However, more research is needed to develop effective therapies and improve early detection methods for NAFLD.