Fig. 2.

NAFLD-associated SNPs involved in liver steatosis. Polymorphisms in NAFLD-related genes cause TG accumulation in the liver through impaired TG hydrolase activities, increased lipogenesis, increased TG synthesis, reduced secretion of TG-rich VLDL, increased lipid droplet formation, STAT3 inactivation, increased liver supply of FFAs, decreased fatty acid oxidation, and decreased irisin secretion. Each gene and its polymorphisms have specific pathways in causing TG accumulation. For instance, polymorphisms in the PNPLA3 gene can impair the TG hydrolase activities, as well as cause an increase in n-6 PUFA level, which stimulate lipogenesis in the liver, resulting in steatosis. Mutations in TCF7L2, SAMM50, IL-6, and AGTR1 promote lipolysis in adipose tissue and skeletal muscle, leading to increased supply of FFAs to the liver, increased de novo lipogenesis, and eventually increased TG accumulation. Changes in MBOAT7 and IL-1B genes cause increased TG synthesis and lipid droplet formation. Meanwhile, the UCP2 gene seems to possess protective effects against steatosis by inducing fatty acid oxidation, lowering the supply of FFAs to the liver. (→: promote; ─|: inhibit; : mutated genes; ↓: decreased; ↑: increased)