Controversially, previous studies have shown that mice lacking the OPN gene are protected by obesity and insulin resistance induced by a 24-week HF diet [32], which is due to a long-term HF diet that alters the microenvironment of mice, which results in a significant increase in various proinflammatory cytokines and immune cells in the fat tissue [33]. The gene discussed is SPP1; the disease is obesity due to melanocortin 4 receptor deficiency.