Energy storage capacity under positive energy balance is important for metabolic health. An increased energy intake, particularly after consuming increased amounts of glucose, fructose, and saturated fat, and when energy expenditure is low, results in the storage of energy mostly in the form of triglycerides in adipose tissue.

An unhealthy diet results in increased hepatic de novo lipogenesis and hepatic inflammation. This process is amplified by a lipodystrophy-like phenotype with expansion of visceral adipose tissue. By increased secretion of very low-density lipoproteins, ceramides, pro-coagulants, glucose, and dysregulated secretion of microRNAs and hepatokines, the fatty liver impacts metabolically important organs and tissues and the cardiovascular system.

Pathophysiological targeted treatment of hepatic steatosis, e.g. by inhibiting cortisol production in metabolically active tissues, such as the liver, is effective to fight the epidemic of NAFLD.