Figure 2.

The liver in the context of MAFLD. Lifestyle and metabolic alterations lead to an increased lipolysis of visceral adipose tissue, stimulating de novo lipogenesis, and an increase in FFA and VLDL (and a consequent efflux of this lipoprotein). Increased glucose intake results in increased pyruvate and Acetyl-CoA production, leading to increased TCA activity. Furthermore, there is augmented β-oxidation resulting in mitochondrial dysfunction. The consequences are mitochondrial dysfunction, altered mtDNA, an imbalance in respiration (reduction in ATP production), and RE stress. All these events are related to increased inflammation and ROS, which results in apoptosis and liver damage. Systemic inflammation occurs due to Kupffer cell activation. DNL: de novo lipogenesis; FFA: free fatty acid; IL: interleukin; JNK: c-Jun N-terminal kinase; M2: macrophage; mtDNA: mitochondrial DNA; NF-KB: nuclear factor-KB, NO: nitric acid; NLRP3: NLR family pyrin domain-containing 3; ROS: reactive oxygen species; VLDL: very-low-density lipoprotein; TG: triglyceride; TNF-α: tumor necrosis factor-α; TCA: tricarboxylic acid cycle.