**1. Introduction**

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders defined by the presence of steatosis in more than 5% of hepatocytes with little or no alcohol consumption [1]. NAFLD is also associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, and metabolic syndrome. Currently, NAFLD is increasing at approximately to be 25% in the general adult population [2–4] and 10% among children [5]. It encompasses six histological subtypes: simple liver steatosis, non-alcoholic steatohepatitis (NASH), non-alcoholic fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation [6]. The global prevalence of NASH has been estimated to range from 3–5%. NAFLD is also associated with increased mortality, particularly due to cardiovascular disease, hepatocellular carcinoma, and liver-related events [7].

All of these complications of NASH can put significant health, economic, and patient-experience burdens to the patients and the society [8].

Hepatic steatosis is the hallmark of NAFLD, which also encompasses hepatic inflammation, hepatocyte damage, and even fibrosis, highlighting the potentially progressive nature of the disease. Although fibrosis also occurs in patients with steatosis alone, NASH has even higher rates of progression and overall mortality in NAFLD [9]. Additionally, hepatic steatosis is associated with metabolic dysfunctions, such as obesity status, insulin resistance, dyslipidemia, and cardiovascular disease [10].

The liver is an essential central regulator of lipid homeostasis organ, which is keeping the balance between lipid acquisition and disposal [11]. The liver acquires lipids through the uptake of circulating fatty acids (FAs) and *via de novo* lipogenesis (DNL) and be disposed of through fatty acid oxidation (FAO) in the mitochondria, peroxisomes, and cytochromes and through export as very low density lipoprotein (VLDL) particles. Lipid accumulation is the result of lipid acquisition pathways exceeding disposal pathways consequently. The disruption of one or more of these pathways may precipitate the retention of fat within the liver and the subsequent development of NAFLD. These processes are closely regulated by complex interactions between hormones, nuclear receptors, and transcription factors, keeping hepatic lipid homeostasis under tight control [12].

However, molecular mechanisms of hepatic lipid homeostasis in NAFLD are not fully elucidated. This chapter explores current insights into these four pathways and the molecular mechanisms regulating the pathological aggregation of NAFLD, discussing processes that may be instrumental in the development and progression of hepatic steatosis.
