It is well known that MetS or obesity commonly leads to NAFLD and hepatocyte lipotoxic injury, and the development of nonalcoholic steatohepatitis, which occur concurrently with the accumulation of insoluble protein aggregates composed of ubiquitinated proteins and the ubiquitin adaptor p62/sequestosome 1. This evidence concerns the gene SQSTM1 and obesity due to melanocortin 4 receptor deficiency.